To see the other types of publications on this topic, follow the link: Cephalosporins – Side effects.
Journal articles on the topic 'Cephalosporins – Side effects'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 45 journal articles for your research on the topic 'Cephalosporins – Side effects.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Shahbaz, Kiran. "Cephalosporins: pharmacology and chemistry." Pharmaceutical and Biological Evaluations 4, no. 6 (December 3, 2017): 234. http://dx.doi.org/10.26510/2394-0859.pbe.2017.36.
Full textAbstract:
Cephalosporins are the most important antibiotics having β-lactam ring and are obtained from a fungus Acremonium, also known as cephalosporium. The wide use of cephalosporins against bacteria in various severe infections such as respiratory tract infection (RTI), skin infection and urinary tract infection (UTI) has led the scientist dive into the detail of this antibacterial drug. The knowledge about structural activity relationship (SAR), spectrum of inhibition (SOI), chemical properties and pharmacology of cephalosporin has pivotal impact to device advanced therapeutic results. The treatment of a disease using cephalosporin has many pros and cons. If the pharmacology and chemical properties of this drug are known properly, many side effects can be diminished or minimized to a certain level. This article review some pharmacological and chemical properties of cephalosporins.
2
Norrby, S. Ragnar. "Side Effects of Cephalosporins." Drugs 34, Supplement 2 (1987): 105–20. http://dx.doi.org/10.2165/00003495-198700342-00009.
Full text
3
Gradl, Gabriele, Johanna Werning, Salka Enners, Marita Kieble, and Martin Schulz. "Quality Appraisal of Ambulatory Oral Cephalosporin and Fluoroquinolone Use in the 16 German Federal States from 2014–2019." Antibiotics 10, no. 7 (July 8, 2021): 831. http://dx.doi.org/10.3390/antibiotics10070831.
Full textAbstract:
Background: Despite concerns about causing bacterial resistance and serious side effects, oral cephalosporins and fluoroquinolones are still frequently prescribed in Germany. We aimed to test a method for the detection of regional quality differences in the use of oral cephalosporins and fluoroquinolones and to apply this to the German federal states. Methods: Use of antibiotics from 2014–2019 was analyzed using dispensing data from community pharmacies claimed to the statutory health insurance (SHI) funds. Quality of regional antibiotic use in 2019 was assessed by calculating indicators based on defined daily doses per 1000 SHI-insured persons per day (DID). Oral cephalosporin and fluoroquinolone use was followed by linear regression analyses. Results: The method used was suitable to find meaningful quality differences in ambulatory oral cephalosporin and fluoroquinolone use between the German federal states. In 2019, DID varied from 1.62 in Brandenburg to 3.17 in Rhineland-Palatinate for cephalosporins and from 0.47 in Brandenburg to 0.89 in Saarland for fluoroquinolones. The city-states Hamburg, Bremen, and Berlin showed highest quality with the applied indicator set. From 2014–2019, a significant decrease in utilization of oral cephalosporins was found in all federal states. During 2017–2019, all states showed a significant decline of fluoroquinolone use.
4
Bathini, Lavanya, Racquel Jandoc, Paul Kuwornu, Eric McArthur, Matthew A. Weir, Manish M. Sood, Marisa Battistella, et al. "Clinical Outcomes of Failing to Dose-Reduce Cephalosporin Antibiotics in Older Adults with CKD." Clinical Journal of the American Society of Nephrology 14, no. 2 (January 10, 2019): 197–205. http://dx.doi.org/10.2215/cjn.10710918.
Full textAbstract:
Background and objectivesCurrent dosing recommendations for cephalosporin antibiotics are on the basis of pharmacokinetic studies and are frequently ignored in practice. This study was undertaken to investigate the clinical outcomes of failing to dose-reduce cephalosporin antibiotics in CKD.Design, setting, participants, & measurementsRetrospective cohort study conducted in Ontario, Canada using linked population-based health care databases. Nine thousand three hundred forty-seven outpatients (median age 83; interquartile range, 77–88 years; 57% women) with an eGFR<30 ml/min per 1.73 m2 and no prior history of dialysis were dispensed oral cephalexin, cefuroxime, or cefprozil between April of 2007 and March of 2016. Two thirds of the patients (6253 of 9347) received a higher than recommended daily dose of cephalexin (>1000 mg), cefuroxime (>500 mg), or cefprozil (>500 mg). The primary outcome was a hospital encounter (emergency room visit or hospital admission) with a condition listed as a possible side-effect of cephalosporins. Secondary outcomes were antibiotic treatment failure and all-cause mortality. All measures were assessed in the 30 days after cephalosporin initiation.ResultsPatients who received a higher than recommended dose of a cephalosporin antibiotic were similar in multiple indicators of baseline health to patients who received a reduced dose. Overall, 6% of patients presented to hospital with a possible cephalosporin side-effect, 13% failed antibiotic treatment, and 3% died. Compared with a reduced dose, receiving a higher dose of antibiotic was not associated with a different rate of side-effects (adjusted odds ratio, 1.00; 95% confidence interval, 0.84 to 1.20), treatment failure (1.01; 0.88 to 1.15), or death (0.99; 0.76 to 1.29).ConclusionsIn this study we failed to demonstrate any association between the dose of cephalosporin antibiotic administered to elderly patients with CKD and the risk of side-effects leading to hospitalization, treatment failure, or mortality.
5
Safadi, Sami, Michael Mao, and John J. Dillon. "Ceftriaxone-Induced Acute Encephalopathy in a Peritoneal Dialysis Patient." Case Reports in Nephrology 2014 (2014): 1–4. http://dx.doi.org/10.1155/2014/108185.
Full textAbstract:
Encephalopathy is a rare side effect of third and fourth generation cephalosporins. Renal failure and preexisting neurological disease are notable risk factors. Recognition is important as discontinuing the offending agent usually resolves symptoms. We present a case of acute encephalopathy in a patient with end stage renal disease (ESRD) treated with peritoneal dialysis (PD) who received intravenous ceftriaxone for peritonitis. This case illustrates the potential severe neurologic effects of cephalosporins, which are recommended by international guidelines as first-line antimicrobial therapy for spontaneous bacterial peritonitis.
6
Marble, Dwight A., and John A. Bosso. "Norfloxacin: A Quinoline Antibiotic." Drug Intelligence & Clinical Pharmacy 20, no. 4 (April 1986): 261–66. http://dx.doi.org/10.1177/106002808602000402.
Full textAbstract:
Norfloxacin is a quinoline (quinolinecarboxylic acid) that should prove successful in treating infections that currently require hospitalization and intravenous antibiotics. Although a nalidixic acid derivative, it possesses greater antibacterial activity against gram-positive and gram-negative bacteria. Compared with other antimicrobial agents, norfloxacin is more potent than the aminoglycosides, first-, second-, and third-generation cephalosporins, tetracycline, trimethoprim-sulfamethoxazole, carbenicillin, piperacillin, nalidixic acid, oxolinic acid, cinoxacin, and enoxacin. In the clinical studies to date, the side effects of norfloxacin have been minimal, but include nausea, vomiting, anorexia, dizziness, headache, drowsiness, depression, and a bitter taste in the mouth. In studies with more than 4000 patients, the incidence of side effects ranged from 3.9 to 4.7 percent, with most appearing by the second day of therapy.
7
Demchenkova, E. Yu, G. I. Gorodetskaya, I. A. Mazerkina, M. V. Zhuravleva, A. S. Kazakov, M. V. Gorodetskiy, L. Yu Badriddinova, and S. Yu Serebrova. "Major Aspects of Detection and Monitoring of Adverse Reactions Associated with Cephalosporin Antibiotic Treatment." Safety and Risk of Pharmacotherapy 9, no. 1 (March 16, 2021): 34–42. http://dx.doi.org/10.30895/2312-7821-2021-9-1-34-42.
Full textAbstract:
Widespread use of cephalosporin antibiotics in clinical practice calls for greater attention to the risk of adverse drug reactions. Information on serious or unexpected adverse events reported during post-marketing experience is submitted to national and international pharmacovigilance databases. Analysis of these reports helps to identify new adverse drug reactions.The aim of the study was to analyse the safety profile of cephalosporin antibiotics based on spontaneous reports in the international VigiBase database.Materials and methods: the analysis of the adverse reaction profile of cephalosporin antibiotics was based on MedDRA system organ classes and included spontaneous reports submitted to VigiBase from the moment of its creation until August 2020.Results: the authors identified the most clinically significant adverse reactions for different cephalosporin generations. They compared and analysed information on adverse events in VigiBase and in patient information leaflets of medicinal products authorised in the Russian Federation. It was demonstrated that some serious events described in VigiBase spontaneous reports for V-generation cephalosporins are not included in the “Side effects” section of the patient information leaflets. According to VigiBase, the use of ceftaroline was associated with the development of generalised exfoliative dermatitis, Stevens–Johnson syndrome, tubulointerstitial nephritis, while the use of ceftolozane was associated with acute kidney injury, renal insufficiency, sepsis, pneumonia, and respiratory insufficiency.Conclusion: reporting of unexpected and serious adverse drug reactions to cephalosporin antibiotics is an important task of healthcare practitioners. Availability of information on class-specific and generation-specific serious adverse reactions will help predict and prevent their development.
8
Leviton, Ira. "Separating Fact from Fiction: The Data Behind Allergies and Side Effects Caused by Penicillins, Cephalosporins, and Carbapenem Antibiotics." Current Pharmaceutical Design 9, no. 12 (May 1, 2003): 983–88. http://dx.doi.org/10.2174/1381612033455143.
Full text
9
Hujer, Andrea M., Kristine M. Hujer, Marion S. Helfand, Vernon E. Anderson, and Robert A. Bonomo. "Amino Acid Substitutions at Ambler Position Gly238 in the SHV-1 β-Lactamase: Exploring Sequence Requirements for Resistance to Penicillins and Cephalosporins." Antimicrobial Agents and Chemotherapy 46, no. 12 (December 2002): 3971–77. http://dx.doi.org/10.1128/aac.46.12.3971-3977.2002.
Full textAbstract:
ABSTRACT Site saturation mutagenesis of the 238 position in the SHV β-lactamase was performed to identify the complete sequence requirements needed for the extended spectrum β-lactamase (ESBL) phenotype. MICs (in micrograms per milliliter) in an isogenic background, Escherichia coli DH10B, demonstrated that the Gly238Ala mutation conferred the most resistance to penicillins and cephalosporins. The absolute increase in resistance was greatest against cefotaxime for the Gly238Ala mutant (0.06 to 8 μg/ml). Except for the strain possessing the Gly238Pro β-lactamase, ceftazidime MICs were also elevated. None of the mutant SHV β-lactamases were expressed in as great an amount as the wild-type β-lactamase. Kinetic analysis of the Gly238Ala mutant revealed that penicillin and cephalosporin substrates have a lower Km for the enzyme because of this mutation. Ampicillin and piperacillin MICs were inversely proportional to the side chain volume of the amino acid in cases larger than Ser, suggesting that steric considerations may be a primary requirement for penicillin resistance. Secondary structural effects explain increased resistance to oxyiminocephalosporins. Based upon this study, we anticipate that additional mutations of Gly238 in the SHV β-lactamase will continue to be discovered with an ESBL (ceftazidime or cefotaxime resistant) phenotype.
10
Lacroix, C., F. Kheloufi, F. Montastruc, Y. Bennis, V. Pizzoglio, and J. Micallef. "Serious central nervous system side effects of cephalosporins: A national analysis of serious reports registered in the French Pharmacovigilance Database." Journal of the Neurological Sciences 398 (March 2019): 196–201. http://dx.doi.org/10.1016/j.jns.2019.01.018.
Full text
11
Hanna, Ramy, Shih-Fan Sun, and Pryce Gaynor. "A Case of Ertapenem Neurotoxicity Resulting in Vocal Tremor and Altered Mentation in a Dialysis Dependent Liver Transplant Patient." Antibiotics 8, no. 1 (December 22, 2018): 1. http://dx.doi.org/10.3390/antibiotics8010001.
Full textAbstract:
Carbapenem agents are advanced derivatives of cephalosporins that are active against bacteria that produce extended spectrum beta lactamases (ESBL). These antibiotics are resistant to enzymatic cleavage, and have good central nervous system penetration. Given this fact, it is not surprising that these drugs have been reported to cause neurological side effects like seizures and encephalopathy. We report a case of a patient on hemodialytic support who had a notable change in mentation and vocal tremor. This was at first attributed to calcineurin toxicity, but after the finding of a normal tacrolimus level, ertapenem neurotoxicity was suspected. After discontinuation of the offending agent, the patient’s vocal tremor, cognition, and neurological function returned to baseline levels.
12
Yemm, Kristyn E., Jason N. Barreto, Ross A. Dierkhising, Kristin C. Mara, Naseema Gangat, and Pritish K. Tosh. "A Comparison of Levofloxacin and Oral Third Generation Cephalosporins As Antibacterial Prophylaxis in Acute Myeloid Leukemia (AML) during Chemotherapy-Induced Neutropenia." Blood 128, no. 22 (December 2, 2016): 3986. http://dx.doi.org/10.1182/blood.v128.22.3986.3986.
Full textAbstract:
Abstract Background: There is demonstrated benefit when administering fluoroquinolones as infection prophylaxis in neutropenic patients; however, side effects, drug interactions and increasing drug resistance necessitate investigation toward safe and effective alternative therapies. This study investigates the use of oral third generation cephalosporins as antibacterial prophylaxis during chemotherapy-induced neutropenia to establish knowledge on alternative treatment options. Methods: A retrospective chart review was performed to compare incidence of febrile neutropenia and documented infection rates in Acute Myeloid Leukemia (AML) and intermediate to high International prognostic scoring system (IPSS) risk myelodysplastic syndrome (MDS) patients receiving antibacterial chemoprophylaxis at Mayo Clinic between January 2006 and April 2016. Patients were included if they were 18 years or older, had a diagnosis confirmed on bone marrow biopsy, received induction or first relapse induction-remission chemotherapy regimens and then subsequently were prescribed fluoroquinolone or an oral third generation cephalosporin prophylaxis for anticipated profound and prolonged neutropenia. The main regimens prescribed were cytarabine + anthracycline (7+3), daunorubicin + cytarabine + nilotinib, mitoxantrone + etoposide + cytarabine, all-trans-retinoic acid (ATRA) + anthracycline, all-trans-retinoic acid (ATRA) + arsenic, clofarabine + cytarabine, or an investigational trial. After meeting inclusion criteria the treatment arms were matched via Charlson comorbidity index ( ± 3) and age ( ± 5). Patients with a documented infection 48 hours after switching from either broad spectrum antibiotics to antibacterial prophylaxis, or from levofloxacin prophylaxis to an oral third generation cephalosporin were excluded from the study. All patients provided consent for review of their medical records for research purposes. This study was approved by the Mayo Foundations institutional review board. Results: A total of 565 patients admitted to Mayo Clinic inpatient leukemia service for chemotherapy and concurrently prescribed antibacterial prophylaxis with either levofloxacin or an oral third generation cephalosporin were screened between January 1, 2006 and April 1, 2016. Of those screened 397 patients met the inclusion criteria, and subsequently 123 patients were matched via Charlson comorbidity index and age. Patient characteristics are presented in Table I. Of the 123 study patients, 80 (65%) were male, and the median age was 58.6 years (IQR: 53.3-68.5). The population was comprised of 115 (93.5%) patients with AML, and 8 (6.5%) patients with MDS. By 30 days after prophylaxis start 109 of the 123 patients developed febrile neutropenia (89.9%, 95% CI: (82.8-94.1)). There was no difference in the risk of febrile neutropenia between those on levofloxacin and those on an oral third generation cephalosporin (hazard ratio [HR] = 1.057, 95% CI: 0.64-1.75, p=0.83). The mean ANC value at the time of febrile neutropenia was 0.47 (SD: 1.4). Documented reasons that patients did not receive an oral fluoroquinolone were QTc prolongation (34.2%), rash (21.1%), tendonitis (2.6%), anaphylaxis (5.3%), drug interaction with a treatment study drug (23.7%), or other (13.1%). Three patients died 30 days or less after the last dose of chemoprophylaxis (40 day survival: 96.6%, 95% CI: 92.7-100); two of the reported deaths were due to infection. Of the 111 patients who had a documented febrile episode, 40 (36%) had a culture positive infection. Gram positive organisms caused 27 (71.1%) of the infections, 11 (28.9%) were gram negative organisms, and 1 (2.6%) infection was due to an anaerobic organism. There were 3 (7.5%) polymicrobial infections, and 36 (90%) monomicrobial infections. The majority of the patients had bloodstream as the documented site of infection. Of the documented culture positive infections 15 (39.5%) showed resistance to levofloxacin and 6 (15.8%) had resistance to third generation cephalosporins when susceptibility testing was reported. Conclusions: These findings demonstrate comparable safety and efficacy of oral third generation cephalosporins compared to fluoroquinolones and contribute to the growing body of literature surrounding antibacterial prophylaxis during chemotherapy-induced neutropenia. Further prospective, randomized investigation is warranted. Disclosures No relevant conflicts of interest to declare.
13
Bush, K. "Beta-lactamase inhibitors from laboratory to clinic." Clinical Microbiology Reviews 1, no. 1 (January 1988): 109–23. http://dx.doi.org/10.1128/cmr.1.1.109.
Full textAbstract:
beta-Lactamases constitute the major defense mechanism of pathogenic bacteria against beta-lactam antibiotics. When the beta-lactam ring of this antibiotic class is hydrolyzed, antimicrobial activity is destroyed. Although beta-lactamases have been identified with clinical failures for over 40 years, enzymes with various abilities to hydrolyze specific penicillins or cephalosporins are appearing more frequently in clinical isolates. One approach to counteracting this resistance mechanism has been through the development of beta-lactamase inactivators. beta-Lactamase inhibitors include clavulanic acid and sulbactam, molecules with minimal antibiotic activity. However, when combined with safe and efficacious penicillins or cephalosporins, these inhibitors can serve to protect the familiar beta-lactam antibiotics from hydrolysis by penicillinases or broad-spectrum beta-lactamases. Both of these molecules eventually inactivate the target enzymes permanently. Although clavulanic acid exhibits more potent inhibitory activity than sulbactam, especially against the TEM-type broad-spectrum beta-lactamases, the spectrum of inhibitory activities are very similar. Neither of these inhibitors acts as a good inhibitor of the cephalosporinases. Clavulanic acid has been most frequently combined with amoxicillin in the orally active Augmentin and with ticarcillin in the parenteral beta-lactam combination Timentin. Sulbactam has been used primarily to protect ampicillin from enzymatic hydrolysis. Sulbactam has been used either in the orally absorbed prodrug form as sultamicillin or as the injectable combination ampicillin-sulbactam. Synergy has been demonstrated for these combinations for most members of the Enterobacteriaceae, although those organisms that produce cephalosporinases are not well inhibited. Synergy has also been observed for Neisseria gonorrhoeae, Haemophilus influenzae, penicillinase-producing Staphylococcus aureus, and anaerobic organisms. These antibiotic combinations have been used clinically to treat urinary tract infections, bone and soft-tissue infections, gonorrhea, respiratory infections, and otitis media. Gastrointestinal side effects have been reported for Augmentin and sultamicillin; most side effects with these agents have been mild. Although combination therapy with beta-lactamase inactivators has been used successfully, the problem of resistance development to two agents must be considered. Induction of cephalosporinases can occur with clavulanic acid. Permeability mutants could arise, especially with added pressure from a second beta-lactam.(ABSTRACT TRUNCATED AT 250 WORDS)
14
Wang, Wen, Wenwen Chen, Yanmei Liu, Reed Alexander C. Siemieniuk, Ling Li, Juan Pablo Díaz Martínez, Gordon H. Guyatt, and Xin Sun. "Antibiotics for uncomplicated skin abscesses: systematic review and network meta-analysis." BMJ Open 8, no. 2 (February 2018): e020991. http://dx.doi.org/10.1136/bmjopen-2017-020991.
Full textAbstract:
ObjectiveTo assess the impact of adjunctive antibiotic therapy on uncomplicated skin abscesses.DesignSystematic review and network meta-analysis.Data sourcesMedline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov.Study selectionA BMJ Rapid Recommendation panel provided input on design, important outcomes and the interpretation of the results. Eligible randomised controlled trials (RCTs) included a comparison of antibiotics against no antibiotics or a comparison of different antibiotics in patients with uncomplicated skin abscesses, and reported outcomes prespecified by the linked guideline panel.Review methodsReviewers independently screened abstracts and full texts for eligibility, assessed risk of bias and extracted data. We performed random-effects meta-analyses that compared antibiotics with no antibiotics, along with a limited number of prespecified subgroup hypotheses. We also performed network meta-analysis with a Bayesian framework to compare effects of different antibiotics. Quality of evidence was assessed with The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsFourteen RCTs including 4198 patients proved eligible. Compared with no antibiotics, antibiotics probably lower the risk of treatment failure (OR 0.58, 95% CI 0.37 to 0.90; low quality), recurrence within 1 month (OR 0.48, 95% CI 0.30 to 0.77; moderate quality), hospitalisation (OR 0.55, 95% CI 0.32 to 0.94; moderate quality) and late recurrence (OR 0.64, 95% CI 0.48 to 0.85; moderate quality). However, relative to no use, antibiotics probably increase the risk of gastrointestinal side effects (trimethoprim and sulfamethoxazole (TMP-SMX): OR 1.28, 95% CI 1.04 to 1.58; moderate quality; clindamycin: OR 2.29, 95% CI 1.35 to 3.88; high quality) and diarrhoea (clindamycin: OR 2.71, 95% CI 1.50 to 4.89; high quality). Cephalosporins did not reduce the risk of treatment failure compared with placebo (moderate quality).ConclusionsIn patients with uncomplicated skin abscesses, moderate-to-high quality evidence suggests TMP-SMX or clindamycin confer a modest benefit for several important outcomes, but this is offset by a similar risk of adverse effects. Clindamycin has a substantially higher risk of diarrhoea than TMP-SMX. Cephalosporins are probably not effective.
15
Jung, In Young, Jung Ju Kim, Se Ju Lee, Jinnam Kim, Hye Seong, Wooyong Jeong, Heun Choi, et al. "Antibiotic-Related Adverse Drug Reactions at a Tertiary Care Hospital in South Korea." BioMed Research International 2017 (2017): 1–7. http://dx.doi.org/10.1155/2017/4304973.
Full textAbstract:
Background. Adverse drug reactions (ADRs) are any unwanted/uncomfortable effects from medication resulting in physical, mental, and functional injuries. Antibiotics account for up to 40.9% of ADRs and are associated with several serious outcomes. However, few reports on ADRs have evaluated only antimicrobial agents. In this study, we investigated antibiotic-related ADRs at a tertiary care hospital in South Korea.Methods. This is a retrospective cohort study that evaluated ADRs to antibiotics that were reported at a 2400-bed tertiary care hospital in 2015. ADRs reported by physicians, pharmacists, and nurses were reviewed. Clinical information reported ADRs, type of antibiotic, causality assessment, and complications were evaluated.Results. 1,277 (62.8%) patients were considered antibiotic-related ADRs based on the World Health Organization-Uppsala Monitoring Center criteria (certain, 2.2%; probable, 35.7%; and possible, 62.1%). Totally, 44 (3.4%) patients experienced serious ADRs. Penicillin and quinolones were the most common drugs reported to induce ADRs (both 16.0%), followed by third-generation cephalosporins (14.9%). The most frequently experienced side effects were skin manifestations (45.1%) followed by gastrointestinal disorders (32.6%).Conclusion. Penicillin and quinolones are the most common causative antibiotics for ADRs and skin manifestations were the most frequently experienced symptom.
16
Shah, haroon M., Erin Guenther, Claire Dysart, Katherine Sherman, and Nathan Gundacker. "595. Characteristics of Antimicrobials Which Affect Parenteral Antibiotic Therapy Outcomes." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S360. http://dx.doi.org/10.1093/ofid/ofaa439.789.
Full textAbstract:
Abstract Background Outpatient parenteral antibiotic therapy (OPAT) has reduced length of stay, decreased nosocomial infections, and improved patient satisfaction/outcomes. Factors for choosing candidates and regimens for OPAT include: type of infection, organisms, antibiotic side effects, number of antibiotics and frequency of administration. This study sought to evaluate if antibiotic type, frequency, and duration, are associated with complications, and particularly if vancomycin is associated with an increase rate of complication. Methods Retrospective chart review of Zablocki VA Medical Center patients, Milwaukee, WI discharged from 2013-2017 on OPAT evaluated types of infection, antimicrobial regimens, number of antibiotics, duration, frequency, adverse events and outcomes. Primary outcome analyzed was whether or not there was a complication. Complication defined as antibiotic change/dose adjustment, PICC line complication, or additional clinic/hospital visit Results 294 cases identified during study period. 286 (95.7%) were male. Most common antibiotics were vancomycin (78; 26.53%), daptomycin (42;14.9%) ertapenem (81, 27.55%), cefazolin (24;8.16%) and ceftriaxone (50;17%). Staphylococcus and Streptococcus were the most common organisms at 42.86% and 22.79% respectively. Univariate analysis of the most common antibiotics, maximum frequency and duration are summarized in table 1. A multivariable found cephalosporins were associated with no complication (OR 2.23, CI 1.20-4.35), and Vancomycin (OR 0.20, CI 0.11-0.36) and Gentamicin (OR 0.06, CI 0.06-0.58) were significantly associated with complication. Antibiotic frequency, duration, bacterial speciation were associated with no complication when controlling for antibiotic type Table 1 Conclusion Antibiotics given for longer durations or require more frequent monitoring like vancomycin may have higher rates of complications. This study supports the hypothesis that vancomycin and aminoglycosides are associated with complications even when controlling for duration and frequency; cephalosporins are associated with no complication. New, safer antibiotics like long acting lipoglycopeptides may provide alternatives to Vancomycin to diminish the burden on ancillary OPAT staff who deal with OPAT complications. Disclosures All Authors: No reported disclosures
17
Canovic, Predrag, Zoran Todorovic, Olgica Gajovic, Ljiljana Nesic, and Zeljko Mijailovic. "Pseudomembranous colitis during antibiotic therapy." Medical review 56, no. 7-8 (2003): 381–83. http://dx.doi.org/10.2298/mpns0308381c.
Full textAbstract:
Introduction The use of antibiotics is commonly accompanied by diarrhea: idiopathic diarrhea with a benign process and diarrhea caused by Clostridium difficile and pseudomembranous colitis. Clostridium difficile colonizes the gastrointestinal tract and produces a toxin in cases when normal flora is suppressed by antibiotics. Pseudomembranous colitis most frequently appears after application of clindamycin, lincomycin, ampicillin, cephalosporins and other antibiotics. Diagnosis is established after rectoscopic findings of adherent pseudomembrane and pathohistological verification. The diagnosis is confirmed if there is evidence of Cl. difficile toxin in feces. Case report We report about the clinical course of two patients with antibiotic-associated colitis. The diagnoses were made by clinical examinations, rectoscopy and pathohistologic verification of biopsy specimen of the intestinal mucosa. Neutralization test was not done due to technical reasons. Patients were treated with metronidazole. Unwanted side-effects of metronidazole therapy were not observed. Discussion Both our patients confirmed that they previously used different antibiotics. In the first case, diarrhea appeared during the antibiotic therapy, and in the second case, after finishing it. After antibiotic use, diarrhea appears in 5.30% cases, but fortunately pseudomembranous colitis is rare. However, taking into consideration that pseudomembranous colitis has a severe course and requires urgent treatment, one has to consider the possibility of pseudomembranous colitis when diarrhea appears during and after antibiotic use in order to initiate adequate therapy.
18
Skagseth, Susann, Trine Josefine Carlsen, Gro Elin Kjæreng Bjerga, James Spencer, Ørjan Samuelsen, and Hanna-Kirsti S. Leiros. "Role of Residues W228 and Y233 in the Structure and Activity of Metallo-β-Lactamase GIM-1." Antimicrobial Agents and Chemotherapy 60, no. 2 (December 7, 2015): 990–1002. http://dx.doi.org/10.1128/aac.02017-15.
Full textAbstract:
ABSTRACTMetallo-β-lactamases (MBLs) hydrolyze virtually all β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. The worldwide emergence of antibiotic-resistant bacteria harboring MBLs poses an increasing clinical threat. The MBL German imipenemase-1 (GIM-1) possesses an active site that is narrower and more hydrophobic than the active sites of other MBLs. The GIM-1 active-site groove is shaped by the presence of the aromatic side chains of tryptophan at residue 228 and tyrosine at residue 233, positions where other MBLs harbor hydrophilic residues. To investigate the importance of these two residues, eight site-directed mutants of GIM-1, W228R/A/Y/S and Y233N/A/I/S, were generated and characterized using enzyme kinetics, thermostability assays, and determination of the MICs of representative β-lactams. The structures of selected mutants were obtained by X-ray crystallography, and their interactions with β-lactam substrates were modeledin silico. Steady-state kinetics revealed that both positions are important to GIM-1 activity but that the effects of individual mutations vary depending on the β-lactam substrate. Activity against type 1 substrates bearing electron-donating C-3/C-4 substituents (cefoxitin, meropenem) could be enhanced by mutations at position 228, whereas hydrolysis of type 2 substrates (benzylpenicillin, ampicillin, ceftazidime, imipenem) with methyl or positively charged substituents was favored by mutations at position 233. The crystal structures showed that mutations at position 228 or the Y233A variant alters the conformation of GIM-1 loop L1 rather than that of loop L3, on which the mutations are located. Taken together, these data show that point mutations at both positions 228 and 233 can influence the catalytic properties and the structure of GIM-1.
19
Hryshchenko, О. V. "Pathogenetic effects of antibiotic resistance on a woman’s reproductive health." Infusion & Chemotherapy, no. 3.2 (December 15, 2020): 66–68. http://dx.doi.org/10.32902/2663-0338-2020-3.2-66-68.
Full textAbstract:
Background. Over the last decade, women in many countries around the world have seen an increase in the number of urogenital infections, which occupy the first place in the structure of obstetric and gynecological morbidity. Risk factors for the development of inflammatory diseases include the invasive procedures and irrigations, sexual activity, unreasonable treatment, refusal to restore eubiosis after antimicrobial and antifungal therapy, the presence of intrauterine devices, etc.
Objective. To characterize the influence of the spread of antibiotic-resistant pathogens on the course of gynecological diseases.
Materials and methods. Analysis of literature data on this issue.
Results and discussion. Peculiarities of the vaginal infections course’ nowadays include prevalence of self-treatment, uncontrolled antibiotics (AB) use, the development of AB resistance, and the presence of extragenital pathology. Pelvic inflammatory disease (PID) comprise 75 % of all gynecological diseases. PID cause such complications as chronic pelvic pain syndrome, purulent tubo-ovarian tumors, cervical neoplasia, and infertility. The risk of the latter increases depending on the number of episodes of PID. Principles of PID treatment include comprehensiveness, etiopathogenetic orientation, individualization and recurrence prevention. Antibacterial therapy (ABT), nonsteroidal anti-inflammatory drugs, infusions, transfusions, detoxification therapy, medications aimed at the improvement of hemodynamics and microcirculation, immunotherapy, and topical therapy are used in the treatment of PID. The consequences of irrational ABT include an increase in the resistance of pathogenic flora, disruption of the normal body biocenosis, increased risk of adverse reactions, impaired immune function and increased treatment costs. Macrolides, cephalosporins, fluoroquinolones and aminoglycosides are the main groups of AB used for the systemic ABT in PID. Tobramycin (one of the latter group) is active against 83.4 % of pathogens that cause urogenital infections. Other advantages of tobramycin include synergism with β-lactams and high activity against Pseudomonas aeruginosa – a bacterium with a high and dangerous potential for AB resistance. In turn, fluoroquinolones are active against 94 % of pathogens that cause urogenital infections; they are able to penetrate cell membranes and have a low potential for the formation of AB resistance. The combination of fluoroquinolone levofloxacin with ornidazole (Grandazole, “Yuria-Pharm”) can improve the general condition and reduce pain on the 3rd day of treatment of PID, normalize the temperature, reduce hospital stay. Co-administration of levofloxacin and ornidazole as part of an infusion solution is more rational than their separate use. Such treatment minimizes the risk of allergic reactions and side effects. For local sanitation of vagina and vulva, it is advisable to use decamethoxine (Dekasan, “Yuria-Pharm”) – a basic antiseptic that acts on various types of bacteria, viruses, fungi and protozoa. Additional benefits are anti-inflammatory, desensitizing and antispasmodic action. Decamethoxine also effectively reduces the adhesion of staphylococci and Escherichia coli. One of the main advantages of decamethoxine is the lack of effect on human cells.
Conclusions. 1. PID are the most common diseases in the field of obstetrics and gynecology. 2. Care should be taken when choosing a drug for ABT. 3. The combination of levofloxacin and ornidazole can effectively treat PID, reducing the duration of inpatient treatment. 4. For local sanitation of the vagina and vulva, it is advisable to use decamethoxine.
20
Shapovalova, M. M., A. V. Budnevsky, A. Ya Kravchenko, E. S. Drobysheva, and E. S. Ovsyannikov. "PATHOGENESIS, ACTUAL ASPECTS OF PREVENTION AND TREATMENT OF THE ANTIBIOTIC-ASSOCIATED DIARRHOEA." Russian Archives of Internal Medicine 8, no. 6 (December 3, 2018): 424–29. http://dx.doi.org/10.20514/2226-6704-2018-8-6-424-429.
Full textAbstract:
The article provides an overview of current Russian and foreign literature devoted to the problem of pathogenesis, and of the treatment and prevention of antibiotic-associated diarrhea. Antibiotic-associated diarrhea is one of the most relevant aspects of modern drug therapy in due to the frequent prescription of antibacterial agents. Antibiotic-associated diarrhea (according to WHO) is defined as the presence of three or more episodes of an unformed stool for two or more consecutive days that occurred during or after the end of antibiotic therapy. The risk of developing this disorder is highest when using aminopenicillins, as well as their combinations with clavulanic acid, cephalosporins, clindamycin. Despite the presence of a common etiologic factor — the intake of antibacterial agents, the immediate causes and mechanisms of antibiotic-associated diarrhea development in patients may be different. The article describes the main issues of the etiology and pathogenesis of this pathology, the risk factors for the development of antibiotic-associated diarrhea are named, that allows to predict this complication in certain categories of patients. Тhe virulence factors of Clostridium difficile, Klebsiella oxytoca, Candida spp. and the clinical manifestations associated with their effects are highlighted. The clinical variants of this disease are described: 1) pseudomembranous colitis; 2) segmental hemorrhagic colitis; 3) “mild illness”. Contemporary literature data on the possibilities of prevention, as well as effective methods of treatment of antibiotic-associated diarrhea, are presented. For the treatment and prevention of all clinical forms of antibiotic-associated diarrhea, most authors suggest the use of drugs that make up the deficiency of normal intestinal microbiota — probiotics and prebiotics. The problem of the benefits of adjuvant therapy with probiotics during the course of antibiotics for the prevention of antibiotic-associated diarrhea remains controversial, the effectiveness and safety of the use of various probiotic cultures for this purpose is being studied. The information presented in this review is intended to target physicians to the rational use of antibacterial agents, and to early diagnosis of their most frequent side effect, antibiotic-associated diarrhea.
21
Thottacherry, Elizabeth, Philip L. Whitfield, Taylor D. Steuber, Chao Li, Adam J. Sawyer, Jonathan Edwards, and Ali Hassoun. "2425. Correlating Use of High-Risk Antimicrobials and the Incidence of Hospital-Onset Clostridium difficile Infection: Targeting Prescribing Trends for Antimicrobial Stewardship." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S838. http://dx.doi.org/10.1093/ofid/ofz360.2103.
Full textAbstract:
Abstract Background Hospital-onset Clostridium difficile infection (HO-CDI) has a significant morbidity and mortality risk. It also poses increasing financial strain on the healthcare system. Certain antibiotics have been associated with increased HO-CDI incidence and novel strategies are needed to determine what modifiable risk factors exist. Choices of antibiotic have changed overtime time to overcome potential side effects, leading to a possibility that changed prescribing trends could be linked to significant differences in the rate of HO-CDI. Methods This study took place at a 971-bed community hospital from January 2016 to January 2018. Monthly utilization (grams) of 11 antimicrobials considered high risk of HO-CDI was collected, along with monthly HO-CDI rate. Antimicrobials included cephalosporins, carbapenems, fluoroquinolones and clindamycin. Correlational (Pearson’s) and logistic regression analyses were completed to identify association with HO-CDI. A P-value of < 0.05 was considered statistically significant. Results 215 cases of HO-CDI were identified during the study period with 30 being classified as severe. The average HO-CDI rate was 4.3 cases/1000 patient-days. There were no significant correlations identified for any antimicrobials and HO-CDI rate (p> 0.05 for all interactions). Pearson’s correlation coefficients were not significant for any antimicrobial. The multivariable logistic regression model including all antimicrobials, indicated that only ceftazidime had a statistically significant positive effect on the HO-CDI rate. Bearing in mind that only a small number of ceftazidime was prescribed, additional univariate analysis was performed indicating that there was no significant linear association between the HO-CDI rate and ceftazidime utilization (P = 0.3527). Conclusion Our study shows that there is no significant correlation between specific antimicrobial use and HO-CDI rates, even though there has been a general increase in HO-CDI rates. Additional analysis involving control groups of antibiotic use in patients without HO-CDI as well as incidence of HO-CDI in patients without antibiotic use at all is required to further assess possible modifiable risk factors in the inpatient population. Disclosures All authors: No reported disclosures.
22
Solheim, Anne Marit, Unn Ljøstad, and Åse Mygland. "Six versus two weeks treatment with doxycycline in Lyme neuroborreliosis: the protocol of a multicentre, non-inferiority, double-blinded and randomised controlled trial." BMJ Open 9, no. 6 (June 2019): e027083. http://dx.doi.org/10.1136/bmjopen-2018-027083.
Full textAbstract:
IntroductionCurrent treatment guidelines for European Lyme neuroborreliosis (LNB) recommend cephalosporins, penicillin or doxycycline for 14–28 days but evidence for optimal treatment length is poor. Treatment lengths in clinical practice tend to exceed the recommendations. Most patients experience a rapid improvement of symptoms and neurological findings within days of treatment, but some report long-term complaints. The underlying mechanisms of remaining complaints are debated, and theories as ongoing chronic infection withBorrelia burgdorferi, dysregulated immune responses, genetic predisposition, coinfection with multiple tick-borne pathogens, structural changes in CNS and personal traits have been suggested. The main purpose of our trial is to address the hypothesis of improved outcome after long-term antibiotic treatment of LNB, by comparing efficacy of treatment with 2 and 6 weeks courses of doxycycline.Methods and analysisThe trial has a multicentre, non-inferiority, double-blinded design. One hundred and twenty patients diagnosed with LNB according to European Federation of Neurological Societies (EFNS)guidelines will be randomised to 6 or 2 weeks treatment with oral doxycycline. The patients will be followed for 12 months. The primary endpoint is improvement on a composite clinical score (CCS) from baseline to 6 months after inclusion. Secondary endpoints are improvements in the CCS 12 months after inclusion, fatigue scored on Fatigue Severity Scale, subjective symptoms on the Patient Health Questionnaire-15 scale, health-related quality of life scored on RAND 36-item short form health survey and safety as measured by side effects of the two treatment arms. Blood and cerebrospinal fluid (CSF) are collected from inclusion and throughout the follow-up and a biobank will be established. The study started including patients in November 2015 and will continue throughout December 2019.Ethics and disseminationThe study is approved by the Norwegian regional committees for medical and health research ethics and the Norwegian Medicines Agency. Data from the study will be published in peer-reviewed medical journals.Trial registration number2015-001481-25
23
Junior, Adelino Freire, Fernando Fagundes, Mozar Castro Neto, Carine Barbosa, and Thais Alves. "Evaluation of Initial Outcomes of an Antimicrobial Stewardship Program in a Nonprofit Hospital in Brazil." Infection Control & Hospital Epidemiology 41, S1 (October 2020): s228—s229. http://dx.doi.org/10.1017/ice.2020.775.
Full textAbstract:
Background: One of the main global public health challenges is the fight against microbial resistance, according to the World Health Organization. Inadequate use of antimicrobials is considered one of the main factors related to the phenomenon and is quite common in the hospital environment. Managing the use of antimicrobials in hospitals has become a necessity and has shown positive results in many ways, such as maximizing the effects of pharmacotherapy, preventing the emergence of resistant microorganisms, and reducing healthcare costs. Methods: The prescriptions for patients admitted to a 380-bed nonprofit private hospital in Belo Horizonte, Brazil were monitored from January 1, 2019, to August 31, 2019, with a monthly average of 251 patients followed by the antimicrobial stewardship (AMS) team (1 infectious diseases doctor and 2 clinical pharmacists). Patients selected for follow-up and intervention were those submitted to intravenous, intramuscular, and/or oral antibiotic therapy with the following antimicrobial agents: piperacillin/tazobactam, carbapenem, polymyxin B, tigecycline, vancomycin, teicoplanin, daptomycin, third- and fourth-generation cephalosporins, quinolone, and aminoglycosides. Patients on prophylactic or antimicrobial treatment not mentioned above were excluded from surveillance. Interventions were dose adjustments, drug adjustment by culture results, intravenous to oral treatment switch, and discontinuation of therapy. Results: There were 318 interventions, and 64.82% of the interventions performed by the AMS team were accepted by prescribers. The interventions provided a total savings of BR$ 119,706 (~US$30,000) in direct antimicrobial spending. Correlating the interventions with the defined daily dose (DDD) measurement and comparing data from the same period in 2018, we detected a reductions in the consumption of several antimicrobials: ceftriaxone (25.6%), ciprofloxacin (45.7%), meropenem (34%), piperacillin/tazobactam (12.7%), teicoplanin (18.8%), vancomycin (20.6%), cefepime (23.9%) and polymyxin B (26%). We also detected reductions in days of therapy (DOT) for most of these drugs, such as polymyxin B, with an average reduction of 2 DOT. Conclusions: Reducing antimicrobial use is one of the key strategies for avoiding unnecessary exposure and selective pressure leading to the emergence of resistant microorganisms. The measured data point to a favorable trend in the rational use of antimicrobials in our institution with simple interventions. The results presented were used to reaffirm the importance of the AMS team in our institution. More data on length of stay, indirect costs, reduction of side effects, mortality, and occurrence of microbial resistance should be made.Funding: NoneDisclosures: None
24
Jones, Ronald N., and Hien M. Nguyen. "1453. Cephalexin and Cefadroxil Are Not Therapeutic Equivalents for Uncomplicated Cystitis (uUTI): Further Analysis of Cefazolin Surrogate Susceptibility Testing Criteria." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S530—S531. http://dx.doi.org/10.1093/ofid/ofz360.1317.
Full textAbstract:
Abstract Background Cephalexin (CLEX) and cefadroxil are first-generation oral cephalosporins (OC’s) with similar antimicrobial spectrums, side-effects, and high urine concentrations; and are US-FDA approved for uUTI. Some stewardship programs are replacing CLEX (4 × daily) with cefadroxil (2 × daily) for dosing convenience. The US Committee on Antimicrobial Susceptibility Testing (USCAST) and CLSI recommend a cefazolin (CZOL) UTI surrogate breakpoint (≤16 mg/L; ≥15 mm) to predict susceptibility (S) for 7 OC’s against indicated Enterobacteriaceae. Direct cefadroxil antimicrobial S testing (AST) does not exist in US breakpoint interpretive documents, limiting specific results. Methods We reanalyzed and compared the CZOL surrogate testing for cefadroxil, CLEX and 5 other OC’s using AST data previously reported (Schuetz et al., 2013; IHMA). Broth microdilution AST was used against 205 isolates: E. coli (92; 40% with β-lactamase), K. pneumoniae (62), P. mirabilis (31; 10% with β-lactamase), and other enteric bacilli (20). A CZOL surrogate S breakpoint (≤16 mg/L) was used to infer S for OC’s. Results CZOL X cefadroxil cross-S accuracy rate was only 91.6% (unacceptable; < 95%) and the false resistance was 1.0% (acceptable). Cross-S accuracy was ≥ 97.0% for all tested OC’s except cefadroxil and cephradine (80.1%). CZOL spectrum vs. tested, indicated species (81.0%) was essentially identical for CLEX, cefprozil, cefaclor and loracarbef (80.0–81.0%). In contrast, cefdinir, cefpodoxime, and cefuroxime axetil S rates were underestimated 5.3 to 10.7% by the surrogate test. CLSI and USCAST did not list cefadroxil or cephradine for CZOL surrogate uUTI prediction; however the current (2019) US-FDA website document states “cefadroxil may be deduced from testing CZOL” regardless of clinical indication. Conclusion Cefadroxil -S for guiding uUTI therapy cannot be accurately predicted by CZOL results at ≤16 mg/L (unacceptable surrogate accuracy and compromised spectrum/potency). Furthermore, direct cefadroxil AST does not exist in United States due to lack of breakpoint criteria (CLSI, USCAST) and reagent materials (MIC products or disks). CLEX or other OC’s remain preferred, more active (table) uUTI treatment choices having quality direct or surrogate AST guidances. Disclosures All authors: No reported disclosures.
25
Simonet, Valérie, Monique Malléa, and Jean-Marie Pagès. "Substitutions in the Eyelet Region Disrupt Cefepime Diffusion through the Escherichia coli OmpF Channel." Antimicrobial Agents and Chemotherapy 44, no. 2 (February 1, 2000): 311–15. http://dx.doi.org/10.1128/aac.44.2.311-315.2000.
Full textAbstract:
ABSTRACT The Escherichia coli OmpF porin is a nonspecific channel involved in the membrane translocation of small hydrophilic molecules and especially in the passage of β-lactam antibiotics. In order to understand the dynamic of charged-compound uptake through bacterial porins, specific charges located in the E. coliOmpF channel were mutated. Substitutions G119D and G119E, inserting a protruding acidic side chain into the pore, decreased cephalosporin and colicin susceptibilities. Cefepime diffusion was drastically altered by these mutations. Conversely, substitutions R132A and R132D, changing a residue located in the positively charged cluster, increased the rate of cephalosporin uptake without modifying colicin sensitivity. Modelling approaches suggest that G119E generates a transverse hydrogen bond dividing the pore, while the two R132 substitutions stretch the channel size. These charge alterations located in the constriction area have differential effects on cephalosporin diffusion and substantially modify the profile of antibiotic susceptibility.
26
Eva, Lucian, Letitia Doina Duceac, Liviu Stafie, Constantin Marcu, Geta Mitrea, Elena Roxana Bogdan Goroftei, Elena Hanganu, et al. "Physical - Chemical Issues of Cephalosporin Intercalated Nanoparticles for Life - Threatening Infections Treatment." Revista de Chimie 71, no. 3 (January 1, 2001): 342–49. http://dx.doi.org/10.37358/rc.20.3.8007.
Full textAbstract:
The fourth generation cephalosporin antibacterial agent, cefepime, was loaded into layered double hydroxides for enhancing antibiotic efficiency, reducing side effects, as well as achieving the sustained release property. The intercalation of antibiotic into the inter-gallery of ZnAl-layered double hydroxide (LDH) was carried out using ion exchange method, by this constituting a nano-sized organic-inorganic hybrid material for a controlled release novel formulation. Although cefepime is a broad spectrum antibiotic, it has various adverse effects and a significant degradation rate. Thus, the preparation and physico-chemical characterization of nanomaterials able to intercalate this drug is an important study for medical and pharmaceutical field. The antibiotic inclusion into LDHs nanostructure was confirmed by advanced characterization techniques and the release profile of cefepime was analysed with the respect to pH of the simulated media.
27
Lamotte-Brasseur, J., G. Dive, O. Dideberg, P. Charlier, J. M. Frère, and J. M. Ghuysen. "Mechanism of acyl transfer by the class A serine β-lactamase of Streptomyces albus G." Biochemical Journal 279, no. 1 (October 1, 1991): 213–21. http://dx.doi.org/10.1042/bj2790213.
Full textAbstract:
Optimization by energy minimization of stable complexes occurring along the pathway of hydrolysis of benzylpenicillin and cephalosporin C by the Streptomyces albus G beta-lactamase has highlighted a proton shuttle that may explain the catalytic mechanism of the beta-lactamases of class A. Five residues, S70, S130, N132, T235 and A237, are involved in ligand binding. The gamma-OH group of T235 and, in the case of benzylpenicillin, the gamma-OH group of S130 interact with the carboxylate group, on one side of the ligand molecule. The side-chain NH2 group of N132 and the carbonyl backbone of A237 interact with the exocyclic CONH amide bond, on the other side of the ligand. The backbone NH groups of S70 and A237 polarize the carbonyl group of the scissile beta-lactam amide bond. Four residues, S70, K73, S130 and E166, and two water molecules, W1 and W2, perform hydrolysis of the bound beta-lactam compound. E166, via W1, abstracts the proton from the gamma-OH group of S70. While losing its proton, the O-gamma atom of S70 attacks the carbonyl carbon atom of the beta-lactam ring and, concomitantly, the proton is delivered back to the adjacent nitrogen atom via W2, K73 and S130, thus achieving formation of the acyl-enzyme. Subsequently, E166 abstracts a proton from W1. While losing its proton, W1 attacks the carbonyl carbon atom of the S70 ester-linked acyl-enzyme and, concomitantly, re-entry of a water molecule W'1 replacing W1 allows E166 to deliver the proton back to the same carbonyl carbon atom, thus achieving hydrolysis of the beta-lactam compound and enzyme recovery. The model well explains the differences found in the kcat. values for hydrolysis of benzylpenicillin and cephalosporin C by the Streptomyces albus G beta-lactamase. It also explains the effects caused by site-directed mutagenesis of the Bacillus cereus beta-lactamase I [Gibson, Christensen & Waley (1990) Biochem J. 272, 613-619].
28
Ngiam, Jinghao Nicholas, Tze Sian Liong, Sai Meng Tham, Thanawin Pramotedham, Rawan AlAgha, Joy Yong, Paul Anantharajah Tambyah, and Lionel Hon Wai Lum. "Deranged Coagulation Profile Secondary to Cefazolin Use: Case Report." Infectious Disease Reports 13, no. 1 (March 1, 2021): 187–90. http://dx.doi.org/10.3390/idr13010021.
Full textAbstract:
Cefazolin is a widely used first-generation cephalosporin. While generally well tolerated, several case reports have described severe coagulopathy induced by intravenous (IV) cefazolin. This was seen particularly in patients with impaired renal function, where antibiotic choice is limited and may require specific dose adjustments. Altered renal handling of antibiotics and their metabolites may potentiate toxicity and side effects. We report a case of a 72-year-old Chinese man who had been treated for methicillin-sensitive staphylococcus aureus (MSSA, coagulase-positive) infective endocarditis with cefazolin and, consequently, developed significantly elevated international normalised ratio (INR) while on therapy. This resolved within 48 h after cessation of cefazolin and administration of oral vitamin K. Malnourished patients with pre-existing or acute kidney injury may be at an increased risk of cefazolin-related coagulopathy.
29
Pujari, Rashmi R., Bhabagrahi Rath, and Tapan Kumar Nayak. "Measurement of antibiotic consumption in surgical ward of a tertiary care hospital." International Journal of Basic & Clinical Pharmacology 9, no. 10 (September 22, 2020): 1565. http://dx.doi.org/10.18203/2319-2003.ijbcp20204097.
Full textAbstract:
Background: Antibiotic resistance is a global health problem. Improper use of antibiotics leads to development of antibiotic resistance, side effects, superinfections and increase in treatment costs. There are few publications on antibiotic consumption. Serious morbidity and mortality are associated with postoperative wound infections. The use of peri or pre-operative antibiotics has resulted in a reduced risk of postoperative infection when appropriate principles of prophylaxis are applied.Methods: An observational study during a 2-month period was carried out in the department of surgery of Veer Surendra Sai Institute of Medical Science and Research, Burla. We utilized the administrative data for expression of antibiotic consumption using anatomical therapeutic classification (ATC) / defined daily dose (DDDs) methodology. The information included were drug names, strength, pharmaceutical form, quantity dispensed, total number of patients admitted during the study period and average length of stay. Each drug was then given a code according to the ATC classification. The number of DDDs and DDDs/100 bed days was calculated.Results: The most frequent antibiotic used was cephalosporin group with DDDs 62.70 DDDs/100 bed days (44.34%) followed by metronidazole with 23.10 DDDs/100 bed days (16.34%). Among cephalosporin group most common antibiotic used was ceftriaxone with 24.46 DDDs/100 bed days. The mean duration of stay was 7.2 days.Conclusions: The results of this study are similar to previous studies and it showed that there is irrational use of antibiotics as there is no antibiotic policy in our hospital. Drug utilization research should be carried out at frequent intervals to improve rational use of antibiotics.
30
Nepal, Hari P., and Rama Paudel. "An overview of carbapenem, its resistance and therapeutic options for infections caused by carbapenem resistant bacteria." International Journal of Basic & Clinical Pharmacology 9, no. 9 (August 25, 2020): 1454. http://dx.doi.org/10.18203/2319-2003.ijbcp20203635.
Full textAbstract:
Carbapenems are beta-lactam drugs that have broadest spectrum of activity. They are commonly used as the drugs of last resort to treat complicated bacterial infections. They bind to penicillin binding proteins (PBPs) and inhibit cell wall synthesis in bacteria. Important members that are in clinical use include doripenem, ertapenem, imipenem, and meropenem. Unlike other members, imipenem is hydrolyzed significantly by renal dehydropeptidase; therefore, it is administered together with an inhibitor of renal dehydropeptidase, cilastatin. Carbapenems are usually administered intravenously due to their low oral bioavailability. Most common side effects of these drugs include nausea, vomiting, diarrhea, skin rashes, and reactions at the infusion sites. Increasing resistance to these antibiotics is being reported throughout the world and is posing a threat to public health. Primary mechanisms of carbapenem resistance include expulsion of drug and inactivation of the drug by production of carbapenemases which may not only hydrolyze carbapenem, but also cephalosporin, penicillin, and aztreonam. Resistance especially among Gram negative bacteria is of much concern since there are only limited therapeutic options available for infections caused by carbapenem resistant Gram-negative bacterial pathogens. Commonly used drugs to treat such infections include polymyxins, fosfomycin and tigecycline.
31
Terada, Tomohiro, Hideyuki Saito, Mayumi Mukai, and Ken-Ichi Inui. "Recognition of β-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells." American Journal of Physiology-Renal Physiology 273, no. 5 (November 1, 1997): F706—F711. http://dx.doi.org/10.1152/ajprenal.1997.273.5.f706.
Full textAbstract:
PEPT1 and PEPT2 are H+-coupled peptide transporters expressed preferentially in the intestine and kidney, respectively, which mediate uphill transport of oligopeptides and peptide-like drugs such as β-lactam antibiotics. In the present study, we have compared the recognition of β-lactam antibiotics by LLC-PK1 cells stably transfected with PEPT1 or PEPT2 cDNA. Cyclacillin (aminopenicillin) and ceftibuten (anionic cephalosporin without an α-amino group) showed potent inhibitory effects on the glycylsarcosine uptake in the PEPT1-expressing cells. Other β-lactams, such as cephalexin, cefadroxil, and cephradine (aminocephalosporins), inhibited modestly the PEPT1-mediated glycylsarcosine uptake. Except for ceftibuten, these β-lactams showed much more potent inhibitions on the glycylsarcosine uptake via PEPT2 than via PEPT1. Comparison of the inhibition constant ( K i) values between cefadroxil and cephalexin suggested that the hydroxyl group at the NH2-terminal phenyl ring increased affinity for both PEPT1 and PEPT2. It is concluded that PEPT2 has a much higher affinity for β-lactam antibiotics having an α-amino group than PEPT1 and that substituents at the NH2-terminal side chain of these drugs are involved in the recognition by both peptide transporters.
32
Puranik, Ameya. "Ceftraixone induced anaphylaxis and death: a case report." International Journal of Basic & Clinical Pharmacology 10, no. 4 (March 22, 2021): 442. http://dx.doi.org/10.18203/2319-2003.ijbcp20211030.
Full textAbstract:
Ceftriaxone, a broad spectrum third generation cephalosporin antibiotic and sulbactam is a beta-lactamase inhibitor. The combination is used for pre-operative surgical prophylaxis for prevention is secondary bacterial infection. We describe a patient who developed anaphylaxis and death soon after intravenous administration of ceftriaxone and sulbactam combination and review similar cases of adverse effects to these class of drugs. The patient was a 68 year old male admitted to surgery ward for obstructed inguinal hernia. He was prescribed injection ceftriaxone and sulbactam combination along with concomitant medication injection pantoprazole and injection metronidazole. The patient was injected injection ceftriaxone and sulbactam, within 15 minutes he suddenly developed anaphylactic shock and died for fluid aspiration in lungs during resuscitation. PubMed was searched for the following terms: anaphylaxis, ceftriaxone, sulbactam. The papers containing these terms and their references were reviewed. Anaphylactic shock caused by ceftriaxone is an uncommon adverse event in patients receiving the drug. However, similar reactions have been observed in some cases in India and world-wide. Clinicians should be aware that anaphylaxis secondary to ceftriaxone and sulbactam combination is a serious death threatening side-effect.
33
Tchapyjnikov, Dmitry, and Matthew W. Luedke. "Cefepime-Induced Encephalopathy and Nonconvulsive Status Epilepticus: Dispelling an Artificial Dichotomy." Neurohospitalist 9, no. 2 (October 15, 2018): 100–104. http://dx.doi.org/10.1177/1941874418803225.
Full textAbstract:
Cefepime is a fourth-generation cephalosporin antibiotic known to have neurotoxic side effects. Recent reports have described patients on cefepime presenting with altered mentation and concurrent triphasic wave discharges on electroencephalogram (EEG). Some have described this clinical presentation as cefepime-induced encephalopathy, while others have termed it as cefepime-induced nonconvulsive status epilepticus (NCSE). We report on 4 patients who developed cefepime-associated altered mentation with triphasic discharges on EEG. A benzodiazepine trial was attempted in 3 of the patients, all of whom had improvement in the frequency of the triphasic discharges, but only 2 of whom demonstrated a concurrent partial and transient improvement in mental status. All 4 patients had normalization of mental status upon discontinuation of cefepime. We provide a literature review of prior cases and propose that these reports, including those labeled as NCSE, are best described as a cefepime-induced encephalopathy with triphasic discharges as opposed to an ictal phenomenon. We contend that aggressive treatment with anti-seizure medications is not warranted and that cefepime discontinuation is the definitive treatment. This case series and review of the literature clarifies a long-standing terminological ambiguity in a unique clinical picture that can be encountered by the neurohospitalist or other providers.
34
Khan, Aftab Ahmad, Rizwan Uppal, Gul E. Rehan, Farhat Khurshid, Khurshid Ahmed, and Hina Zaib. "EFFECTIVENESS OF CONVENTIONAL ANTIBIOTICS IN SALMONELLA TYPHI POSITIVE BLOOD CULTURES." Journal of Medical Sciences 28, no. 4 (December 31, 2020): 318–22. http://dx.doi.org/10.52764/jms.20.28.4.2.
Full textAbstract:
Abstract:
Objective:
1.To determine the pattern of resistance of salmonella Typhi strains to multiple antibiotics in Islamabad and adjoining areas.
2.Suggestions regarding the regular upgradation of antibiogram according to the most susceptible strains.
Method:
Cross sectional study conducted for duration of one year ,recruited those patients whose blood cultures were found positive for Salmonella Typhi at Islamabad Diagnostic Center. We analyzed 100 samples and Positive culture were then assessed for sensitivity by using various antibiotics and pattern of resistance was analyzed.
Results:
Majority of positive patients were male and children. Sensitivity to the conventional antibiotics was found to be more in children. In all the positive isolates, 89% were sensitive to the first line treatment options.Among them, 96.6%were showing sensitivity to third generation cephalosporin. However, a few cases were having extensively drug resistant patterns (XDR).
Conclusion:
Despite the fact that extensively drug resistantstrains are emerging and indicating an alarming situation,its found out that more than 80% of patients are responding to the conventional therapy,making it a dire need for upgradation of antibiograms, so that the side effects of second line and advanced antibiotic can be avoided, mostly in paediatric population.
35
Magri, Vittorio, Matteo Boltri, Tommaso Cai, Roberto Colombo, Salvatore Cuzzocrea, Pieter De Visschere, Rosanna Giuberti, et al. "Multidisciplinary approach to prostatitis." Archivio Italiano di Urologia e Andrologia 90, no. 4 (January 18, 2019): 227–48. http://dx.doi.org/10.4081/aiua.2018.4.227.
Full textAbstract:
The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. “Next generation” investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called “dysbiosis” causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.
36
Yusuf, Erlangga, Hannelore I. Bax, Nelianne J. Verkaik, and Mireille van Westreenen. "An Update on Eight “New” Antibiotics against Multidrug-Resistant Gram-Negative Bacteria." Journal of Clinical Medicine 10, no. 5 (March 4, 2021): 1068. http://dx.doi.org/10.3390/jcm10051068.
Full textAbstract:
Infections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.S. Food and Drug Administration (FDA) with predominant activities against Gram-negative bacteria. We aimed to review these antibiotics: plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam. Temocillin is an antibiotic that was only approved in Belgium and the UK several decades ago. We reviewed the in vitro activities of these new antibiotics, especially against ESBL and CPE microorganisms, potential side effects, and clinical studies in complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associatedpneumonia (HAP/VAP). All of these new antibiotics are active against ESBL, and almost all of them are active against CPE caused by KPC beta-lactamase, but only some of them are active against CPE due to MBL or OXA beta-lactamases. At present, all of these new antibiotics are approved by the U.S. Food and Drug Administration for cUTI (except eravacycline) and most of them for cIAI (eravacycline, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam) and for HAP or VAP (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam).
37
Erdem, Hakan, Ayşegül Ulu-Kilic, Selim Kilic, Mustafa Karahocagil, Ghaydaa Shehata, Necla Eren-Tulek, Funda Yetkin, et al. "Efficacy and Tolerability of Antibiotic Combinations in Neurobrucellosis: Results of the Istanbul Study." Antimicrobial Agents and Chemotherapy 56, no. 3 (December 12, 2011): 1523–28. http://dx.doi.org/10.1128/aac.05974-11.
Full textAbstract:
ABSTRACTNo data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P= 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n= 5/166, 3.0%) and the oral therapy (n= 4/42, 9.5%) (P= 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n= 6/166 [3.6%] versusn= 6/42 [14.3%];P= 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%,n= 6/42) compared to P1 (2.6%,n= 3/117) and P3 (6.1%,n= 3/49) (P= 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.
38
Snawerdt, Jessica, Sarah Withers, and John Schrank. "460. Ceftriaxone vs. Standard of Care for Definitive Treatment of Methicillin-Susceptible Staphylococcus aureus Infections." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S226. http://dx.doi.org/10.1093/ofid/ofz360.533.
Full textAbstract:
Abstract Background β-Lactam antibiotics, specifically nafcillin, oxacillin, and cefazolin, have proven efficacy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Outpatient antimicrobial therapy (OPAT) with these agents is limited due to side effects and multiple doses required per day. Ceftriaxone, a third-generation cephalosporin, has a favorable profile for OPAT. Limited evidence supporting ceftriaxone therapy for MSSA infections prevents its widespread use. Methods A multi-center, retrospective cohort study comparing patients who received cefazolin or nafcillin to patients who received ceftriaxone for treatment of microbiologically proven MSSA infections was conducted from February 2016 to February 2018. The primary outcome of interest was a clinical success, defined as the absence of infection-related readmission, worsening infection, or recurrent infection within 90 days. Secondary outcomes included the rate of adverse reactions, length of stay, and impact of Infectious Diseases (ID) consult. Results 66 patients treated with ceftriaxone and 156 patients treated with cefazolin or nafcillin were included. Skin and soft tissue and bone and joint were the most common infections in the ceftriaxone group, whereas bacteremia was most common in the nafcillin and cefazolin group. There were significant differences in baseline age (61 years vs. 59 years; P = 0.036) and intravenous drug use (1 patient vs. 25 patients; P = 0.002) between groups. As shown in Table 1, there were significantly lower rates of clinical success with ceftriaxone compared with standard of care as a composite of all infection sites (78.8% vs. 91%; P = 0.012). No statistically significant differences were seen in safety outcomes or ID consultation. Length of stay was significantly longer in the nafcillin and cefazolin group (5.2 days vs. 12.8 days; P ≤ 0.0001). Conclusion The results of this study indicate that patients treated with ceftriaxone for MSSA infections had significantly lower rates of clinical success compared with standard of care antibiotics. Nafcillin or cefazolin should remain as first-line agents for treatment of bone and joint infections and skin and soft-tissue infections due to MSSA. Disclosures All authors: No reported disclosures.
39
OBILIŞTEANU, Gabriela C., Alexandru MATEI, Loredana MANOLESCU, Viviana DRAGODAN, Ruxandra ULMEANU, and Florin D. MIHĂLŢAN. "Updated therapies in bronchiectasis." Romanian Journal of Medical Practice 12, no. 2 (June 30, 2017): 91–96. http://dx.doi.org/10.37897/rjmp.2017.2.6.
Full textAbstract:
Objective. The aim of this study is to evaluate the constantly updated and integrated treatment strategies for the improvement and the cure of bronchiectasis, with a beneficial effect on the quality of life of patients diagnosed with this disease. Material and method. The retrospective study (december 17th 2014 – june 2nd 2015), was conducted on 89 patients hospitalised in the Pneumophtysiology Institute "Marius Nasta" in Bucharest, with the confirmed clinical diagnosis of non cystic fibrosis bronchiectasis. From the clinical observation charts of the patients included in the study, we evaluated the treatment strategies applied for each patient in correlation with the confirmed clinical diagnosis. The therapies applied included antimicrobial, mucolytic, bronchodilator, corticosteroid, immunotherapy treatment, pulmonary rehabilitation, treatment of associated disease (ORL and gastro-oesophageal reflux), hygiene diet and antidepressant treatment. Results. The microbial etiology identified in the sputum (17,97%) consisted of Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus parainfluenzae, Streptococcus pyogenes and Candida albicans, 82,03% of the cases presented non-specific (normal) flora. The associated therapy of antibiotic treatment (cephalosporin + fluoroquinolone) + mucolytic agent (erdosteine) + corticosteroid & β adrenergic agonist + anticolinergic agent + nonsteroid anti-inflammatory + anti-influenza vaccination + immunotherapy was the most efficient and the most used first-intention therapeutic association (35/39,32%). All the patients were discharged with improved bronchiectatic status. Discussions. The present study, with multiple date regarding the treatment of the acute disease, revealed the importance and the benefit of the multitype therapy, continuously updated, for the treatment of bronchiectasis of various degrees of severity. In time, the treatment can have serious side effects for the patient and the community in regard to antibiotic resistance; the severity and the complications' risk offers an useful background for taking clinical decisions that patients require long term treatment courses, such as macrolides, airway adjuvants, inhalatory antibiotics and other measures. Conclusions. Future studies should refer to a greater number of patients with varying degrees of severity of this disease, with more specific etiological information and with a longer duration, to clarify the actual benefits of new promising therapies and to offer new perspectives on the medical approach of bronchiectasis.
40
Jin, Wanchun, Jun-ichi Wachino, Yoshihiro Yamaguchi, Kouji Kimura, Anupriya Kumar, Mototsugu Yamada, Akihiro Morinaka, et al. "Structural Insights into the TLA-3 Extended-Spectrum β-Lactamase and Its Inhibition by Avibactam and OP0595." Antimicrobial Agents and Chemotherapy 61, no. 10 (July 24, 2017). http://dx.doi.org/10.1128/aac.00501-17.
Full textAbstract:
ABSTRACT The development of effective inhibitors that block extended-spectrum β-lactamases (ESBLs) and restore the action of β-lactams represents an effective strategy against ESBL-producing Enterobacteriaceae. We evaluated the inhibitory effects of the diazabicyclooctanes avibactam and OP0595 against TLA-3, an ESBL that we identified previously. Avibactam and OP0595 inhibited TLA-3 with apparent inhibitor constants (Ki app) of 1.71 ± 0.10 and 1.49 ± 0.05 μM, respectively, and could restore susceptibility to cephalosporins in the TLA-3-producing Escherichia coli strain. The value of the second-order acylation rate constant (k 2/K, where k 2 is the acylation rate constant and K is the equilibrium constant) of avibactam [(3.25 ± 0.03) × 103 M−1 · s−1] was closer to that of class C and D β-lactamases (k 2/K, <104 M−1 · s−1) than that of class A β-lactamases (k 2/K, >104 M−1 · s−1). In addition, we determined the structure of TLA-3 and that of TLA-3 complexed with avibactam or OP0595 at resolutions of 1.6, 1.6, and 2.0 Å, respectively. TLA-3 contains an inverted Ω loop and an extended loop between the β5 and β6 strands (insertion after Ser237), which appear only in PER-type class A β-lactamases. These structures might favor the accommodation of cephalosporins harboring bulky R1 side chains. TLA-3 presented a high catalytic efficiency (k cat/Km ) against cephalosporins, including cephalothin, cefuroxime, and cefotaxime. Avibactam and OP0595 bound covalently to TLA-3 via the Ser70 residue and made contacts with residues Ser130, Thr235, and Ser237, which are conserved in ESBLs. Additionally, the sulfate group of the inhibitors formed polar contacts with amino acid residues in a positively charged pocket of TLA-3. Our findings provide a structural template for designing improved diazabicyclooctane-based inhibitors that are effective against ESBL-producing Enterobacteriaceae.
41
Roy, Chinnu, Shaji George, Aleena Issac, Arya Ponnappan, and Dhanya Paul. "Assessment of antimicrobial use in private and government hospitals, a comparative study in central kerala, using who indicators." International Journal of Indigenous Herbs and Drugs, August 31, 2021, 88–92. http://dx.doi.org/10.46956/ijihd.v6i4.236.
Full textAbstract:
Background: Irrational use of antimicrobial can cause various unwanted and untoward events. It may diminish the quality of patient care, increase the cost of therapy, and involvement in various side effects. Thus, the appropriateness of antimicrobial use in hospitals plays a pivotal role in patient safety.
Objective: To analyze and assess the prescribing pattern of antimicrobials in private and government hospitals as per the WHO indicators.
Methodology: A prospective comparative observational study was carried out for 6 months, with the patient diagnosed with an infectious disease admitted to the medical ward of both the hospitals during the study period. The data obtained from the study sites were Compared and analyzed using WHO indicators described in WHO’s “How to Investigate Antimicrobial use in Hospitals: Selected Indicators, Feb 2012”.
Results: The study involved 216 patients and the average number of antimicrobials prescribed was found to be 1.73 in a private hospital and 2.07 in the government hospital, average cost of antimicrobials was found to be 86.48 INR in private and 31.04 INR in the government hospital, average duration of antimicrobial treatment was 4.8 in private and 5.2 in the government hospital, and the percentage of antimicrobials prescribed in generic was 33.33% in private and 87.83% in the government hospital. Considering the spectrum of antibiotics, both private (94.7%) and government (88.8%) used broad-spectrum antimicrobials. In both hospitals, cephalosporins were the most frequently prescribed class of antimicrobials. Comparing the dosage of antimicrobials given, injection usage is at the highest in government (59.5%) as well as in the private hospital (68.4%).
Conclusion: This study indicates that the average cost of antimicrobials was more in a private hospital than that in a government hospital and other indicators such as the number of antimicrobials per hospitalization, duration of antimicrobial treatment, and the percentage of generic antimicrobials prescribed were all found to be more in a government hospital. In both private and government hospitals broad-spectrum antimicrobials were widely used, with cephalosporin as the most prescribed class.
42
Mergenhagen, Kari A., Bethany A. Wattengel, Megan K. Skelly, Collin M. Clark, and Thomas A. Russo. "Fact versus Fiction: a Review of the Evidence behind Alcohol and Antibiotic Interactions." Antimicrobial Agents and Chemotherapy 64, no. 3 (December 23, 2019). http://dx.doi.org/10.1128/aac.02167-19.
Full textAbstract:
ABSTRACT Many antibiotics carry caution stickers that warn against alcohol consumption. Data regarding concurrent use are sparse. An awareness of data that address this common clinical scenario is important so health care professionals can make informed clinical decisions and address questions in an evidence-based manner. The purpose of this systematic review was to determine the evidence behind alcohol warnings issued for many common antimicrobials. The search was conducted from inception of each database to 2018 using PubMed, Medline via Ovid, and Embase. It included studies that involved interactions, effects on efficacy, and toxicity/adverse drug reactions (ADR) due to concomitant alcohol consumption and antimicrobials. All interactions were considered in terms of three components: (i) alteration in pharmacokinetics/pharmacodynamics (PK/PD) of antimicrobials and/or alcohol, (ii) change in antimicrobial efficacy, and (iii) development of toxicity/ADR. Available data support that oral penicillins, cefdinir, cefpodoxime, fluoroquinolones, azithromycin, tetracycline, nitrofurantoin, secnidazole, tinidazole, and fluconazole can be safely used with concomitant alcohol consumption. Data are equivocal for trimethoprim-sulfamethoxazole. Erythromycin may have reduced efficacy with alcohol consumption, and doxycycline may have reduced efficacy in chronic alcoholism. Alcohol low in tyramine may be consumed with oxazolidinones. The disulfiram-like reaction, though classically associated with metronidazole, occurs with uncertain frequency and with varied severity. Cephalosporins with a methylthiotetrazole (MTT) side chain or a methylthiodioxotriazine (MTDT) ring, ketoconazole, and griseofulvin have an increased risk of a disulfiram-like reaction. Alcohol and antimicrobial interactions are often lacking evidence. This review questions common beliefs due to poor, often conflicting data and identifies important knowledge gaps.
43
Kokai-Kun, John F., Tracey Roberts, Olivia Coughlin, Eric Sicard, Marianne Rufiange, Richard Fedorak, Christian Carter, et al. "The Oral β-Lactamase SYN-004 (Ribaxamase) Degrades Ceftriaxone Excreted into the Intestine in Phase 2a Clinical Studies." Antimicrobial Agents and Chemotherapy 61, no. 3 (January 4, 2017). http://dx.doi.org/10.1128/aac.02197-16.
Full textAbstract:
ABSTRACT SYN-004 (ribaxamase) is a β-lactamase designed to be orally administered concurrently with intravenous β-lactam antibiotics, including most penicillins and cephalosporins. Ribaxamase's anticipated mechanism of action is to degrade excess β-lactam antibiotic that is excreted into the small intestine. This enzymatic inactivation of excreted antibiotic is expected to protect the gut microbiome from disruption and thus prevent undesirable side effects, including secondary infections such as Clostridium difficile infections, as well as other antibiotic-associated diarrheas. In phase 1 clinical studies, ribaxamase was well tolerated compared to a placebo group and displayed negligible systemic absorption. The two phase 2a clinical studies described here were performed to confirm the mechanism of action of ribaxamase, degradation of β-lactam antibiotics in the human intestine, and were therefore conducted in subjects with functioning ileostomies to allow serial sampling of their intestinal chyme. Ribaxamase fully degraded ceftriaxone to below the level of quantitation in the intestines of all subjects in both studies. Coadministration of oral ribaxamase with intravenous ceftriaxone was also well tolerated, and the plasma pharmacokinetics of ceftriaxone were unchanged by ribaxamase administration. Since ribaxamase is formulated as a pH-dependent, delayed-release formulation, the activity of ribaxamase in the presence of the proton pump inhibitor esomeprazole was examined in the second study; coadministration of these drugs did not adversely affect ribaxamase's ability to degrade ceftriaxone excreted into the intestine. These studies have confirmed the in vivo mechanism of action of ribaxamase, degradation of β-lactam antibiotics in the human intestine (registered at ClinicalTrials.gov under NCT02419001 and NCT02473640).
44
Habiburrahman, Muhammad, Vivian Soetikno, Wani Riselia Sirait, and Missy Savira. "Solithromycin as A Potential Novel Antibiotic Against Neisseria Gonorrhoeae Resistance." Indonesian Journal of Pharmacy, December 28, 2020. http://dx.doi.org/10.22146/ijp.1123.
Full textAbstract:
Gonorrhea is one of the most often sexually transmitted infection in the world. In 2016, WHO stated the Southeast Asia region as the fourth-highest incidence rate and prevalence of gonorrhea. One of the current problems with gonorrhea is related to its emerging resistance to first-line drugs such as cephalosporins, macrolides, and fluoroquinolones. This resistance has an impact on the difficulty of finding effective antibiotics to eradicate the infection, thus risking financial loss and infertility in sexually active age patients. This literature review will discuss solithromycin, the first fluoroketolide in phase III clinical trial, and show its potential as a new antibiotic against infection with resistant Neisseria gonorrhoeae. Literatures are searched using Pubmed and Google Scholar search engines with keywords: antibiotics, CEM-101, clinical trial, Neisseria gonorrhoeae, new treatment, pharmacology, pharmacokinetics, resistance, safety, and solithromycin. This semisynthetic antibiotic is supported by a different chemical structure from previous macrolides; improving solithromycin becomes more stable and able to bind easier with bacterial ribosomes. Pharmacologically, solithromycin provides an advantage in its high bioavailability, easy oral administration route, wide distribution, metabolism mainly in the liver, but not required dosage adjustments due to hepatic impairment, and a single dosage preparation that can increase patient compliance in healing gonorrhea infections. Also, its lower MIC50 than previous antibiotics makes it well-tolerated, therefore making this antibiotic as a potential recommendation for the management of multi-drug resistant gonorrhea in the future. Solithromycin is not inferior to the standard therapy (ceftriaxone and azithromycin), with 80% vs. 84% gonorrhea eradication rates. Per the anatomic site, the eradication rate is 92% in genital, 94% in the pharynx, and 83% in the rectum. However, special attention needs to be paid to the side effects of the gastrointestinal tract of solithromycin, as observed in phase III clinical trials at a dose of 1000 mg in the form of diarrhea (24%) and nausea (21%).
45
Sadikov, Nematullo, Xu Chao Yue, Xin Zhi Hong, Bekzod Odilov, and Zhang Zhao Hua. "The Effectiveness of Using Prednisolone in Children with Community – Acquired Pneumonia." Asian Journal of Pediatric Research, March 15, 2021, 1–8. http://dx.doi.org/10.9734/ajpr/2021/v5i330173.
Full textAbstract:
Community-acquired Pneumonia (CAP) is an infection of the lung parenchyma that is acquired outside of hospital, [1] involved approximately 150 million new cases annually, among children younger than 5 years old worldwide. We retrospectively evaluated the effect of Prednisolone in 89 children with CAP who were admitted to the 2nd hospital of Shandong University (China) and Infectious diseases of Andijon region (Uzbekistan). The mean age was 6.3 in China (Placebo) and 9.3 in Uzbekistan (control) years, 54% and 52% of them were boys respectively. All children had received broad spectrum antibiotics (cephalosporin) or Macrolides (Azithromycin) and Oxygen. In addition to these we added Prednisolone 1 mg/kg on day 2 of admission to control group. 24 (68.5% from all febrile) children were became afebrile within 24 hours after Predisolone use on day 3 of admission, and their clinical status developed in control group, when it was achieved on day 7 in Placebo group. Hospital days also shortened in control group (6 days) than placebo (8 days) (p value ≤ 0.01). In conclusion, steroid therapy helpful for reducing hospital stay and morbidity in children with community-acquired Pneumonia and no observed side effects.