Journal articles: 'Cephalosporins'

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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.

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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.

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Aiswarya P. Nath, Arul Balasubramanian, and Kothai Ramalingam. "Cephalosporins : An imperative antibiotic over the generations." International Journal of Research in Pharmaceutical Sciences 11, no. 1 (January 20, 2020): 623–29. http://dx.doi.org/10.26452/ijrps.v11i1.1866.

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Cephalosporins are the most commonly prescribed class of antibiotics, and its structure and pharmacology are similar to that of penicillin. It's a bactericidal, and its structure contains beta-lactam ring, as like of penicillin, which intervenes in bacterial cell wall synthesis. Cephalosporins are derived from the mold Acremonium (previously called as Cephalosporium). It was first discovered in 1945; scientists have been improving the structure of cephalosporins to make it more effective against a wider range of bacteria. Whenever the structure of cephalosporins modified, a new "generation" of cephalosporins are made. So far, there are five generations of cephalosporins available. They are prescribed against various organisms and infections. The cephalosporin antibiotics interfere with cell-wall synthesis of bacteria, leading to the breakdown of the infectious organism. To achieve this effect, the antibiotic must cross the bacterial cell wall and bind to the penicillin-binding proteins. Various generations of cephalosporins, mechanisms of resistance, pharmacokinetics, adverse reactions, and their clinical use were reviewed in this article. Most of the cephalosporins are available as parenteral, but the oral formulations are also available for certain drugs. Rather than learn all cephalosporins, it is reasonable for the clinician to be familiar with selected cephalosporins among the parenteral and oral formulations.

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Karadurmus, Leyla, Kaan Eşme, Nurgul K. Bakirhan, and Sibel A. Ozkan. "Recent Electrochemical Assays on Cephalosporins." Current Pharmaceutical Analysis 16, no. 4 (April 27, 2020): 337–49. http://dx.doi.org/10.2174/1573412915666190523120431.

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: Antibiotics are an important class among drugs because they are a significant agent to deal with infections. Cephalosporins are a very important group of antibiotics in the β-lactam class. The cephalosporins are semisynthetic antibiotics derived from products of the fungus Cephalosporium. Cephalosporins are classified as first, second, third, fourth, and advanced generation, based largely on their antibacterial spectrum and stability to β-lactamases. Electrochemical methods have been used for the determination of cephalosporin just as used in the determination of many antibiotic drugs. Electroanalytical methods present generally high sensitivity, low cost, low requirements, ease of preparation of the samples in a very short time, and a short analysis time. The most commonly used types are cyclic voltammetry, differential pulse voltammetry, square wave voltammetry and linear sweep voltammetry. The aim of this review is to evaluate the advantages and uses of electroanalytical methods used in the determination of cephalosporins. In addition, current applications of the methods to the pharmaceutical analysis of cephalosporins will also be summarized in a table.

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Chaudhry, Saira B., Michael P. Veve, and Jamie L. Wagner. "Cephalosporins: A Focus on Side Chains and β-Lactam Cross-Reactivity." Pharmacy 7, no. 3 (July 29, 2019): 103. http://dx.doi.org/10.3390/pharmacy7030103.

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Cephalosporins are among the most commonly prescribed antibiotic classes due to their wide clinical utility and general tolerability, with approximately 1–3% of the population reporting a cephalosporin allergy. However, clinicians may avoid the use of cephalosporins in patients with reported penicillin allergies despite the low potential for cross-reactivity. The misdiagnosis of β-lactam allergies and misunderstanding of cross-reactivity among β-lactams, including within the cephalosporin class, often leads to use of broader spectrum antibiotics with poor safety and efficacy profiles and represents a serious obstacle for antimicrobial stewardship. Risk factors for cephalosporin allergies are broad and include female sex, advanced age, and a history of another antibiotic or penicillin allergy; however, cephalosporins are readily tolerated even among individuals with true immediate-type allergies to penicillins. Cephalosporin cross-reactivity potential is related to the structural R1 side chain, and clinicians should be cognizant of R1 side chain similarities when prescribing alternate β-lactams in allergic individuals or when new cephalosporins are brought to market. Clinicians should consider the low likelihood of true cephalosporin allergy when clinically indicated. The purpose of this review is to provide an overview of the role of cephalosporins in clinical practice, and to highlight the incidence of, risk factors for, and cross-reactivity of cephalosporins with other antibiotics.

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Versporten, Ann, Robin Bruyndonckx, Niels Adriaenssens, Niel Hens, Dominique L. Monnet, Geert Molenberghs, Herman Goossens, et al. "Consumption of cephalosporins in the community, European Union/European Economic Area, 1997–2017." Journal of Antimicrobial Chemotherapy 76, Supplement_2 (July 1, 2021): ii22—ii29. http://dx.doi.org/10.1093/jac/dkab174.

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Abstract Objectives Data on cephalosporin consumption in the community were collected from 30 EU/EEA countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of the main subgroups of cephalosporins. Methods For the period 1997–2017, data on consumption of cephalosporins (i.e. first-, second-, third- and fourth-generation cephalosporins; ATC subgroups J01DB, J01DC, J01DD and J01DE, respectively) in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Cephalosporin consumption was analysed based on ATC-4 subgroup, and presented as trends, seasonal variation, presence of change-points and compositional changes. Results In 2017, cephalosporin consumption in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 285 between countries with the highest (Greece) and the lowest (the Netherlands) consumption. Cephalosporin consumption did not change significantly between the first quarter of 1997 and the last quarter of 2017. Seasonal variation decreased significantly over time. Proportional consumption of second- and third-generation cephalosporins significantly increased over time compared with that of first-generation cephalosporins, and proportional consumption of fourth-generation cephalosporins significantly decreased compared with that of second- and third-generation cephalosporins. Conclusions Despite considerable variation between countries in the composition of cephalosporin consumption and trends over time, a significant shift towards consumption of more broad-spectrum cephalosporins in the community was observed across the EU/EEA during 1997–2017.

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Atanaskovic-Markovic, Marina, and Branimir Nestorovic. "Allergy to cephalosporin antibiotics in children." Srpski arhiv za celokupno lekarstvo 131, no. 3-4 (2003): 127–30. http://dx.doi.org/10.2298/sarh0304127a.

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A particular problem is the safety of administering cephalosporins to penicillin-allergic children, because cephalosporin allergenic determinants have not been properly identified. Cephalosporin antibiotics are widely used to treat common infections and are often the first-line prophylaxis before many types of surgery. So the arm of this study is to determine the frequency of allergic reactions of anaphylactic type to cephalosporins and their cross-reactivity with penicillins. At University Children?s Hospital in Belgrade a group of 1,170 children with suspected anaphylactic allergic reaction to penicillins and/or cephalosporins were tested for the last eight years. Skin tests were performed with standard concentration of penicillins and cephalosporins. In children where skin tests were negative single-blind placebo-controlled challenges were performed. In case of positive skin tests further examinations were interrupted and the children were considered allergic to that drug. The frequency of anaphylactic allergic reactions to cephalosporins is 0.2 % to 17 %, and depends on cephalosporins generation. The cross-reactivity between cephalosporins and penicillins is 0.1 % to 14.5 %, and among cephalosporins is 0 % to 11.7 %.

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Djorić, Dušanka, and Christopher J. Kristich. "Oxidative Stress Enhances Cephalosporin Resistance of Enterococcus faecalis through Activation of a Two-Component Signaling System." Antimicrobial Agents and Chemotherapy 59, no. 1 (October 20, 2014): 159–69. http://dx.doi.org/10.1128/aac.03984-14.

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ABSTRACTEnterococcus faecalisis a low-GC Gram-positive bacterium, a normal resident of the gastrointestinal (GI) tract, and an important hospital-acquired pathogen. An important risk factor for hospital-acquired enterococcal infections is prior therapy with broad-spectrum cephalosporins, antibiotics that impair cell wall biosynthesis by inhibiting peptidoglycan cross-linking. Enterococci are intrinsically resistant to cephalosporins; however, environmental factors that modulate cephalosporin resistance have not been described. While searching for the genetic determinants of cephalosporin resistance inE. faecalis, we unexpectedly discovered that oxidative stress, whether from external sources or derived from endogenous metabolism, drives enhanced intrinsic resistance to cephalosporins. A particular source of oxidative stress, H2O2, activates signaling through the CroR-CroS two-component signaling system, a known determinant of cephalosporin resistance inE. faecalis. We find that CroR-CroS is required for adaptation to H2O2stress and that H2O2potentiates the activities of cephalosporins againstE. faecaliswhen the CroR-CroS signaling system is nonfunctional. Rather than directly detecting H2O2, our data suggest that the CroR-CroS system responds to cell envelope damage caused by H2O2exposure in order to promote cell envelope repair and enhanced cephalosporin resistance.

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Hameed, Tahir K., and Joan L. Robinson. "Review of the Use of Cephalosporins in Children with Anaphylactic Reactions from Penicillins." Canadian Journal of Infectious Diseases 13, no. 4 (2002): 253–58. http://dx.doi.org/10.1155/2002/712594.

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OBJECTIVE: It is a widely accepted practice that children with anaphylaxis from penicillins should avoid cephalosporins. The purpose of the present study was to determine whether there is evidence in the literature to support this practice.DATA SOURCES: MEDLINE, EMBASE, Toxline, Inter-national Pharmaceutical Abstracts and PubMed were used to search the literature published from 1966 to 2001. The Canadian Medical Protective Association, Health Canada and the Boston Collaborative Drug Surveillance Program were also contacted to determine whether there were any unpublished cases of cross-reactivity between penicillins and cephalosporins.DATA EXTRACTION: Cases describing the use of cepha-losporins in adults and children with positive penicillin skin tests or anaphylaxis from penicillin were evaluated. Case reports of anaphylaxis from cephalosporins in paediatric patients were identified.DATA SYNTHESIS: There have been five reported cases of serious reactions from cephalosporins in patients with a history of anaphylaxis from penicillins. All cases occurred in adults; three developed anaphylaxis from the older, first-generation cephalosporins, cephalothin and cephaloridine; one developed anaphylaxis from cefamandole; and one developed anaphylaxis from cefaclor. There have been 12 other published reports of anaphylaxis from cephalosporins in adults with a history of penicillin allergy or a positive penicillin skin test, but with no history of anaphylaxis from penicillin. In seven studies, in which a total of 158 patients with positive penicillin skin tests were administered cephalosporins, seven had apparent immunoglobulin E-mediated reactions when they were given a cephalosporin. When the class of cephalosporin was able to be determined, none of the reports of reactions from cephalosporins in patients with allergies to penicillin involved third-generation cephalosporins. There have been 13 case reports of anaphylaxis from cephalosporins in paediatric patients.CONCLUSIONS: There are no published case reports of anaphylaxis from cephalosporins in children with anaphylaxis from penicillin, and there are only a small number of such reports in adults. Anaphylaxis from cephalosporins appears to be incredibly rare in children. There is minimal evidence in the literature to support the avoidance of cephalosporins in children with anaphylaxis from penicillins.

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Kaye, Keith S., Sara Cosgrove, Anthony Harris, George M. Eliopoulos, and Yehuda Carmeli. "Risk Factors for Emergence of Resistance to Broad-Spectrum Cephalosporins among Enterobacterspp." Antimicrobial Agents and Chemotherapy 45, no. 9 (September 1, 2001): 2628–30. http://dx.doi.org/10.1128/aac.45.9.2628-2630.2001.

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ABSTRACT Among 477 patients with susceptible Enterobacter spp., 49 subsequently harbored third-generation cephalosporin-resistantEnterobacter spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk [OR] = 2.3, P = 0.01); quinolone therapy was protective (OR = 0.4, P = 0.03). There were trends toward decreased risk for resistance among patients receiving broad-spectrum cephalosporins and either aminoglycosides or imipenem. Of the patients receiving broad-spectrum cephalosporins, 19% developed resistance.

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Darville, Toni, and Terry Yamauchi. "The Cephalosporin Antibiotics." Pediatrics In Review 15, no. 2 (February 1, 1994): 54–62. http://dx.doi.org/10.1542/pir.15.2.54.

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Introduction The first cephalosporin released for clinical use was cephalothin in 1964. Since that time, more than 20 cephalosporin antibiotics have been introduced. These are the most commonly prescribed antibiotics in the United States and account for the largest share of hospital expenditures. To determine which agent to use for an infection in a particular patient involves weighing competing claims of improved antibacterial spectrum, side effects, pharmacokinetics, and cost. This review will address these issues, as well as the basic mechanisms of action of the cephalosporins and their mechanisms of bacterial resistance. In addition, instances in which cephalosporins serve as appropriate alternatives or in which they offer distinct advantages over previously available antimicrobial agents will be described. Chemistry and Mechanism of Action Cephalosporins resemble penicillins (Fig.1) in that they have a β-lactam structure, but the five-member thiazolidine ring characteristic of the penicillins is replaced by a six-member dihydrothiazine ring (Fig. 2). The dihydrothiazine ring of the cephalosporins provides the molecule with the ability to resist bacterial enzymes; the antibacterial activity emanates from the β-lactam ring shared by penicillins and cephalosporins. Modifications at position 7 of the cephalosporin nucleus generally affect the antibacterial spectrum, and substitutions at position 3 of the dihydrothiazine ring alter the pharmacokinetics and metabolic parameters of the drug.

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Sfakinos, John. "Detecting the dual presence of AmpC and ESBL enzymes." Microbiology Australia 30, no. 5 (2009): 208. http://dx.doi.org/10.1071/ma09208.

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Inducible-chromosomal AmpC cephalosporinase enzymes have been recognised for several years in the ESCAPPM (Enterobacter spp., Serratia spp., Citrobacter freundii, Acinetobacter spp., Proteus vulgaris, Providencia spp. and Morganella morganii) group of gram-negative organisms, which result in the potential resistance to third-generation cephalosporin drugs. More recently several non-ESCAPPM Enterobacteriaceae (particularly E coli, Klebsiella and Proteus mirabilis) have been found to harbour a non-inducible-plasmid form of AmpC. This is particularly important when found in bacteremic patients where third-generation cephalosporins are often the first line drugs of choice.

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Albrecht, Harry A., George Beskid, Nafsika H. Georgopapadakou, Dennis D. Keith, Frederick M. Konzelmann, David L. Pruess, Pamela L. Rossman, Chung Chen Wei, and James G. Christenson. "Dual-action cephalosporins: cephalosporin 3'-quinolone carbamates." Journal of Medicinal Chemistry 34, no. 9 (September 1991): 2857–64. http://dx.doi.org/10.1021/jm00113a026.

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Botnarciuc, Mihaela, Irina Stan, and Sorina Ispas. "Cephalosporin resistant bacterial strains isolated from respiratory infections." ARS Medica Tomitana 21, no. 1 (February 1, 2015): 7–11. http://dx.doi.org/10.1515/arsm-2015-0012.

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Abstract Objectives: The objective of the study is the evaluation of the actual resistance to second, third, and fourth generation cephalosporins over bacterial strains isolated from respiratory infections. The main causes for cephalosporin resistance of pathogenic and conditioned pathogen bacteria are: widespread usage, and impair immune response. Materials and methods: The analyzed specimens were throat swabs and sputum, from adult patients. The tests were performed using disk diffusion technique. We tested the following cephalosporin: From second generation: cefuroxime axetil; from third generation: cefotaxime, ceftazidime, cefpodoxime; Combinations of cephalosporins and beta-lactamase inhibitors: cefotaxime + clavulanic acid; ceftazidim + clavulanic acid; From fourth generation: cefepime; and association cefepime and clavulanic acid. Results: The following bacterial strains were isolated: Staphylococcus aureus, Streptococcus pneumoniae, Group C β-hemolytic Streptococcus, E. coli, Klebsiella pneumoniae and Proteus sp. The Group A. β-hemolytic Streptococcus isolated strains were not tested. For Staphylococcus aureus, E. coli, K. pneumoniae and Proteus, we found a high frequency resistance tocefuroxim, approximately 47%. Highest resistance to third generation cephalosporin was identified to E.coli and Klebsiella pneumoniae, especially resistant to cefotaxime, cefotaxime + clavulanic acid and ceftazidime. Conclusions: Cefpodoxime can be considered as a first election antibiotic in treating upper and lower respiratory tract infections, due to the lowest level of bacterial strain resistance, approximately 10% of the third generation cephalosporines tested. Also, cefepime may be proper in treating severe respiratory tract infections, with resistant broad-spectrum antibiotics bacterial strains. In our trial, resistance to cefepime was to a minimum low, approximately 4%, represented by the E.coli strains.

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Kemi Busayo Fapetu, Oluwatosin Bola Ojo, and Adekemi Oyagade Oluyege. "A retrospective study on the rate of prescription and resistance to cephalosporin in a hospital in Ado-ekiti, Nigeria." International Journal of Science and Research Archive 6, no. 2 (August 30, 2022): 206–11. http://dx.doi.org/10.30574/ijsra.2022.6.2.0172.

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The rate of prescription of cephalosporins especially the second and third generation and the spread of resistance among members of Enterobacteriaceae has become a reason for concern. This study was designed to determine the rate of prescription and resistance to the 2nd and 3rd-generation cephalosporins to Enterobacteriaceae in the Ekiti State University Teaching Hospital, Ado Ekiti. A retrospective study of prescription forms and laboratory reports were used in collecting the data. A total of 9,234 prescriptions issue within May 2017 to May 2018 were collected. Five thousand five hundred and twenty one (59.8%) prescriptions sheets contain at least one antibiotic. Three thousand seven hundred and thirteen prescriptions 3,713 (40.2%) did not contain any antibiotics. It was observed that Cephalosporins were the most commonly prescribed, while tetracycline was the least with 1584(28.7%) and 1076(19.5%) respectively. Cefuroxime had the highest rate of prescription with 898(57.9%) while cefpodoxime was the least prescribed with 33(2.1%). Out of the 201 diagnosed infections in patients who used cephalosporins, 83 (41.3%) were caused by members of Enterobacteriaceae. E.coli was the most common cause of infections of all the members of Enterobacteriacea with 32.5%. Of all the members of Enterobacteriaceae, 64.2% were resistant to cephalosporin. E.coli had the highest resistance to cephalosporins while Salmonella sp had the lowest resistance with 34(22.5%) and 13(8.6%) respectively. The data obtained from this study showed that there is a significant difference between the rate of prescription of cephalosporins and other antibiotics. Also there was an excessive prescription of the second and third generation cephalosporins. In conclusion the rate of prescription of cephalosporin should be properly checked and laboratory investigations should be properly conducted before administration.

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Park, Gi Hyue, Seungyeon Kim, Min Soo Kim, Yun Mi Yu, Gun Hee Kim, Jeong Sang Lee, and Euni Lee. "The Association Between Cephalosporin and Hypoprothrombinemia: A Systematic Review and Meta-Analysis." International Journal of Environmental Research and Public Health 16, no. 20 (October 16, 2019): 3937. http://dx.doi.org/10.3390/ijerph16203937.

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Cephalosporins that contain the N-methylthiotetrazole side chain (NMTT-cephalosporin) have been reported to be associated with coagulation-related adverse events; however, a comprehensive evaluation regarding the association is lacking. A systematic review and meta-analysis were conducted to assess the safety profile of NMTT-cephalosporins with respect to hypoprothrombinemia and bleeding. The MEDLINE, Embase, Cochrane, and RISS databases were systematically searched for clinical studies up to October 2018. The association between NMTT-cephalosporins and hypoprothrombinemia was estimated using an odds ratio (OR) with a 95% confidence interval (CI). A total of 15 studies on cefamandole, cefoperazone, cefotetan, cefmetazole, and moxalactam were identified and included in the meta-analysis. Hypoprothrombinemia (OR 1.676, 95% CI 1.275–2.203) and prothrombin time (PT) prolongation (OR 2.050, 95% CI 1.398–3.005) were significantly associated with NMTT-cephalosporins, whereas bleeding was not (OR 1.359, 95% CI 0.920–2.009). Subgroup analyses revealed that cefoperazone (OR 2.506, 95% CI 1.293–4.860), cefamandole (OR 3.247, 95% CI 1.083–9.733), and moxalactam (OR 3.367, 95% CI 1.725–6.572) were significantly associated with hypoprothrombinemia. An Antimicrobial Stewardship Program led by a multidisciplinary team could play a critical role in monitoring cephalosporin-related hypoprothrombinemia or PT prolongation in patients with underlying clinical conditions at risk for bleeding. The multidisciplinary team could also assist in communicating the potential safety concerns regarding NMTT-cephalosporin use with healthcare professionals to decrease the risk of adverse events.

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Choi, Sang-Ho, Yang Soo Kim, Jin-Won Chung, Tae Hyong Kim, Eun Ju Choo, Mi-Na Kim, Baek-Nam Kim, Nam Joong Kim, Jun Hee Woo, and Jiso Ryu. "SerratiaBacteremia in a Large University Hospital: Trends in Antibiotic Resistance During 10 Years and Implications for Antibiotic Use." Infection Control & Hospital Epidemiology 23, no. 12 (December 2002): 740–47. http://dx.doi.org/10.1086/502004.

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Objective:To identify antibiotic resistance trends and risk factors for resistance ofSerratiaspecies to third-generation cephalosporins.Design:Retrospective survey of medical records.Setting:A 2,200-bed, tertiary-care hospital.Patients:One hundred twenty-two patients withSerratiabacteremia between January 1991 and June 2001.Methods:Infectious disease physicians collected data from medical records regarding patient demographics, underlying disease or condition, portal of entry, microorganism, antibiogram, complications, antibiotics received, and outcome.Results:Among 122Serratiaisolates, 117 (95.9%) wereSerratiamarcescens and 110 (90.2%) were of nosocomial origin. During the study period, the 122 isolates showed a high rate of resistance to third-generation cephalosporins (45.9%) and extended-spectrum penicillins (56.6%). The resistance rate to ciprofloxacin was 32.0%. The resistance rate to third-generation cephalosporins increased from 31.7% for 1991 to 1995 to 54.9% for 1996 to 1998 and 50.0% for 1999 to 2001. In the multivariate analysis, prior use of a second-generation cephalosporin (adjusted odds ratio [OR], 5.90; 95% confidence interval [CI95], 1.41 to 24.6;P= .015) or a third-generation cephalosporin (OR, 3.26; CI95, 1.20 to 8.87;P= .020) was a strong independent risk factor for resistance to third-generation cephalosporins. The overall case-fatality rate was 25.4% (Serratiabacteremia-related case-fatality rate, 13.1%).Conclusion:Prior use of a second- or third-generation cephalosporin was the most important risk factor for bacteremia withSerratiaresistant to third-generation cephalosporins, suggesting the need for antibiotic control. The potential role of patient-to-patient spread could not be fully evaluated in this retrospective study.

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Pawloy, Karola, Anne Marie Fenstad, Tesfaye Leta, Geir Hallan, Jan-Erik Gjertsen, Håvard Dale, Stein Atle Lie, and Ove Furnes. "No difference in risk of revision due to infection between clindamycin and cephalosporins as antibiotic prophylaxis in cemented primary total knee replacements: a report from the Norwegian Arthroplasty Register 2005–2020." Acta Orthopaedica 94 (July 31, 2023): 404–9. http://dx.doi.org/10.2340/17453674.2023.16907.

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Background and purpose: Systemic antibiotic prophylaxis with clindamycin, which is often used in penicillin- or cephalosporin-allergic patients’, has been associated with a higher risk of surgical revision for deep prosthetic joint infection (PJI) than cloxacillin in primary total knee replacement (TKR). We aimed to investigate whether clindamycin increases the risk of surgical revisions due to PJI compared with cephalosporins in primary cemented TKR.Patients and methods: Data from 59,081 TKRs in the Norwegian Arthroplasty Register (NAR) 2005–2020 was included. 2,655 (5%) received clindamycin and 56,426 (95%) received cephalosporins. Cox regression analyses were performed with adjustment for sex, age groups, diagnosis, and ASA score. Survival times were calculated using Kaplan–Meier estimates and compared using Cox regression with revision for PJI as endpoint. The cephalosporins cefalotin and cefazolin were also compared.Results: Of the TKRs included, 1.3% (n = 743) were revised for PJI. 96% (n = 713) had received cephalosporins and 4% (n = 30) clindamycin for perioperative prophylaxis. Comparing cephalosporins (reference) and clindamycin, at 3-month follow-up the adjusted hazard ratio rate (HRR) for PJI was 0.7 (95% confidence interval [CI] 0.4–1.4), at 1 year 0.9 (CI 0.6–1.5), and at 5 years 0.9 (CI 0.6–1.4). Analysis using propensity score matching showed similar results. Furthermore, comparing cefalotin (reference) and cefazolin, HRR was 1.0 (CI 0.8–1.4) at 3 months and 1.0 (CI 0.7–1.3) at 1-year follow-up.Conclusion: We found no difference in risk of revision for PJI when using clindamycin compared with cephalosporins in primary cemented TKRs. It appears safe to continue the use of clindamycin in penicillin- or cephalosporin-allergic patients.

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Chaulk, Jennifer, Michelle Carbonneau, Hina Qamar, Adam Keough, Hsiu-Ju Chang, Mang Ma, Deepali Kumar, and Puneeta Tandon. "Third-Generation Cephalosporin-Resistant Spontaneous Bacterial Peritonitis: A single-Centre Experience and Summary of Existing Studies." Canadian Journal of Gastroenterology and Hepatology 28, no. 2 (2014): 83–88. http://dx.doi.org/10.1155/2014/429536.

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BACKGROUND: Spontaneous bacterial peritonitis (SBP) is the most prevalent bacterial infection in patients with cirrhosis. Although studies from Europe have reported significant rates of resistance to third-generation cephalosporins, there are limited SBP-specific data from centres in North America.OBJECTIVE: To evaluate the prevalence of, predictors for and clinical impact of third-generation cephalosporin-resistant SBP at a Canadian tertiary care centre, and to summarize the data in the context of the existing literature.METHODS: SBP patients treated with both antibiotics and albumin therapy at a Canadian tertiary care hospital between 2003 and 2011 were retrospectively identified. Multivariate logistic regression was used to determine independent predictors of third-generation cephalosporin resistance and mortality.RESULTS: In 192 patients, 25% of infections were nosocomial. Forty per cent (77 of 192) of infections were culture positive; of these, 19% (15 of 77) were resistant to third-generation cephalosporins. The prevalence of cephalosporin resistance was 8% with community-acquired infections, 17% with health care-associated infections and 41% with nosocomial acquisition. Nosocomial acquisition of infection was the only predictor of resistance to third-generation cephalosporins (OR 4.0 [95% CI 1.04 to 15.2]). Thirty-day mortality censored for liver transplantation was 27% (50 of 184). In the 77 culture-positive patients, resistance to third-generation cephalosporins (OR 5.3 [1.3 to 22]) and the Model for End-stage Live Disease score (OR 1.14 [1.04 to 1.24]) were independent predictors of 30-day mortality.CONCLUSIONS: Third-generation cephalosporin-resistant SBP is a common diagnosis and has an effect on clinical outcomes. In an attempt to reduce the mortality associated with resistance to empirical therapy, high-risk subgroups should receive broader empirical antibiotic coverage.

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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.

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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.

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Albrecht, Harry A., George Beskid, James G. Christenson, Joanne W. Durkin, Virve Fallat, Nafsika H. Georgopapadakou, Dennis D. Keith, Frederick M. Konzelmann, and Ellen R. Lipschitz. "Dual-action cephalosporins: cephalosporin 3'-quaternary ammonium quinolones." Journal of Medicinal Chemistry 34, no. 2 (February 1991): 669–75. http://dx.doi.org/10.1021/jm00106a031.

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Marsh, T. Donald. "The Cephalosporin Antibiotic Agents— III. Third-Generation Cephalosporins." Infection Control 6, no. 2 (February 1985): 78–83. http://dx.doi.org/10.1017/s0195941700062652.

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The third-“generation” cephalosporin antibiotics (Table 1) represent a class of agents with an expanded gram-negative spectrum of activity beyond that of the first- and second-“generation” cephalosporins. Greater stability to beta-lactamases produced by gram-negative organisms confers to these agents a greater bactericidal action against the Enterobacteriaceae. Large bacterial inocula (105/ml) in vitro significantly increase the minimum inhibitory and bactericidal concentrations (MIC and MBC) explaining treatment failures with these agents in infections associated with large numbers of organisms. The pharmacokinetic features of some of the agents allow prolongation of dosing intervals, and enhanced tissue penetration amplifies their clinical utility in infections distant from the bloodstream (eg, meningitis).

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Ommurugan, Dr Balaji, Dr Navin Patil, Dr Amod Tilak, and Dr Avinash A. "CEFUROXIME-INDUCED THROMBOCYTOPENIA: IT’S JUST NOT IN THE RING??" Asian Journal of Pharmaceutical and Clinical Research 9, no. 5 (September 1, 2016): 1. http://dx.doi.org/10.22159/ajpcr.2016.v9i5.13112.

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ABSTRACTBeta lactams are one of the most commonly used antibiotic groups in clinical practice, owing to their relatively superior safety profile, when weighed against other available antibiotics. Cephalosporins have overgrown over the years, now extending across five generations of drugs. Older cephalosporins are still commonly used, chiefly because of their low cost and minimal adverse effects. However, no drug is entirely free of adverse effects. Cephalosporins (especially those with a methylthiotetrazole ring) have been associated with bleeding manifestations due to hypoprothrombinemia and thrombocytopenia in susceptible subsets of the global population. This case report concerns the use of a cephalosporin that does not have this ring in its structure, but has still caused a rare instance of thrombocytopenia

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Vesić, Dušanka, and Christopher J. Kristich. "MurAA Is Required for Intrinsic Cephalosporin Resistance of Enterococcus faecalis." Antimicrobial Agents and Chemotherapy 56, no. 5 (January 30, 2012): 2443–51. http://dx.doi.org/10.1128/aac.05984-11.

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ABSTRACTEnterococcus faecalisis a low-GC Gram-positive bacterium that is intrinsically resistant to cephalosporins, antibiotics that target cell wall biosynthesis. To probe the mechanistic basis for intrinsic resistance, a library of transposon mutants was screened to identifyE. faecalisstrains that are highly susceptible to ceftriaxone, revealing a transposon mutant with a disruption inmurAA. murAAis predicted to encode a UDP-N-acetylglucosamine 1-carboxyvinyl transferase that catalyzes the first committed step in peptidoglycan synthesis: phosphoenolpyruvate (PEP)-dependent conversion of UDP-N-acetylglucosamine to UDP-N-acetylglucosamine-enolpyruvate. In-frame deletion ofmurAA, but not its homolog in theE. faecalisgenome (murAB), led to increased susceptibility ofE. faecalisto cephalosporins. Furthermore, expression ofmurAAenhanced cephalosporin resistance in anE. faecalismutant lacking IreK (formerly PrkC), a key kinase required for cephalosporin resistance. Further genetic analysis revealed that MurAA catalytic activity is necessary but not sufficient for this role. Collectively, our data indicate that MurAA and MurAB have distinct roles inE. faecalisphysiology and suggest that MurAA possesses a unique property or activity that enables it to enhance intrinsic resistance ofE. faecalisto cephalosporins.

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Li, Xinran, Mingjuan Yang, Yuehua Ke, Mingyuan Liu, Yufei Wang, Shiwei Liu, Liu Bo, and Zeliang Chen. "Hfq mutation confers increased cephalosporin resistance in Klebsiella pneumoniae." Archives of Biological Sciences 69, no. 1 (2017): 61–69. http://dx.doi.org/10.2298/abs160126078l.

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Klebsiella pneumoniae (K. pneumoniae), is an opportunistic pathogen raising significant public health concerns owing to its multi-drug resistance. Hfq, one of the main RNA-binding proteins, is a key post-transcriptional regulator. This protein is closely related to virulence and resistance in various pathogenic bacteria. Although the role of hfq in K pneumoniae virulence has been explored, its influence on resistance remains largely unknown. The aim of this study was to investigate the role of hfq in the resistance of K. pneumoniae to cephalosporins. An hfq mutant was constructed, and its resistance to cephalosporins was investigated. The hfq mutant exhibited over 16-fold higher cephalosporin resistance than that exhibited by the wild type. Time-kill curve analysis showed that the hfq mutant could survive under higher concentrations of cephalosporins than the wild-type strain could. Quantitative RT-PCR showed that expression levels for 8 out of the 9 penicillin-binding proteins, which are the targets of cephalosporins, were downregulated in the hfq mutant. Taken together, contrary to its role in many other bacteria, hfq is involved in a negative regulation of K. pneumoniae resistance to cephalosporins by downregulating the expression of penicillin-binding proteins.

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Sakagami, Kenji, Mitsuru Tashiro, Yasuo Takeuchil, and Minoru Hatanaka. "Synthesis of new tricyclic cephalosporins from cephalosporin 3′-triphenylphosphorane." J. Chem. Soc., Perkin Trans. 1, no. 7 (1991): 1766–67. http://dx.doi.org/10.1039/p19910001766.

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ALBRECHT, H. A., G. BESKID, J. G. CHRISTENSON, N. H. GEORGOPAPADAKOU, D. D. KEITH, F. M. KONZELMANN, D. L. PRUESS, P. L. ROSSMAN, and C. C. WEI. "ChemInform Abstract: Dual-Action Cephalosporins: Cephalosporin 3′-Quinolone Carbamates." ChemInform 23, no. 10 (August 22, 2010): no. http://dx.doi.org/10.1002/chin.199210294.

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M. Alwan, Shakir, and Ameer H. Kadhim. "Synthesis of New Cephalosporins of Expected Improved Activity and Resistance Against -Lactamases." Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) 23, no. 2 (March 27, 2017): 24–32. http://dx.doi.org/10.31351/vol23iss2pp24-32.

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The development of new cephalosporins with improved activity against resistant microbes, such as, MRSA (methicillin resistant Staph. aureus), P. aeruginosa, is of high potential. Chemical synthesis of two new series of thiadiazole linked to cysteine (series 1) and cephalosporins containing thiadiazole linked to cysteine through disulfide bond (series 2) were achieved. The chemical structures of the synthesized compounds were confirmed using spectral (FT-IR, 1H-NMR) and elemental microanalysis. The incorporation of privileged chemical moieties, such as, thiadiazole, Schiff base, cysteine and sulfonamide, has been found to have great contribution to the antimicrobial activities. Compounds of series 1 (1b-d), containing a Schiff base or a sulfonamido moiety, showed reasonable activity and were less potent than cephalexin with respect to E. coli and Staph. aureus. The new cephalosporins (series 2) showed remarkable activities on E. coli (62.5-15.6Âµg/ml) and staph. aureus (31.2-62.5Âµg/ml) when compared with cephalexin (250 and 125 Âµg/ml) respectively. Moreover, compounds 1 and 3 showed very promising activity against MRSA (250 and 500Âµg/ml) respectively. The incorporation of a sulfonamido moiety to the cephalosporin molecule was successfully achieved. This is a very interesting finding which may open a new approach in the synthesis of newer cephalosporins. Keywords: Cephalosporins, Cysteine, Schiff base, Sulfonamides, Thiadiazole.

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Vishwajith. "Comparison of in-vitro Antibiotic Susceptibility of Ciprofloxacin, Cefotaxime, Ceftazidime and Cefepime against Gram Negative Bacilli Infections - A Study from Tertiary Care Centre." Journal of Medical Sciences and Health 9, no. 1 (July 8, 2023): 64–69. http://dx.doi.org/10.46347/jmsh.v9i1.22.369.

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Introduction: Infections from gram negative bacilli is a challenge for clinicians and laboratory personnel. Treatment of these infections remained as an area of concern. Both fluroquinolones and cephalosporins are most common choice of antibiotics. Despite Cephalosporins, being drug of choice they are expensive also showed many adverse reactions. This study, compares and reevaluates the susceptibility of gram negative bacteria to fluroquinolones (ciprofloxacin) compared to cephalosporins. Method: Various samples(pus, sputum, urine, blood and bodyfluids) were processed according to standard protocols. Antibiotic done susceptibility by using Kirby-baur disc diffusion method. ESBL and Amp C producers were identified using CLSI guidelines. Result: Among 400 isolates, majority were from pus followed by urine, sputum. The most common organism isolated was Klebsiella spp, (33.25%) Escherichia coli (29.5%), Pseudomonas spp (27.25%), Enterobacter spp (6.25%), Citrobacter 5 (1.25%), and Acinetobacter spp (2.5%). Isolates showed 20-80% susceptibility to ciprofloxacin, 30-60% to third and fourth generation cephalosporins. Klebsiella and Pseudomonas showed 64% and 31% susceptibility to ciprofloxacin. Acinetobacter spp showed 30% susceptibility to cefipime and 20% to ciprofloxacin. 34 isolates were ESBL 18 were AmpC producers, of which 15(44%) ESBL and 7(38%) of AmpC producers were ciprofloxacin susceptible. Conclusion: Ciprofloxacin was found to be more effective than the fourth generation cephalosporin (cefepime) against gram negative bacilli. Ciprofloxacin can be considered for treatment as it is more active and cost effective when compared to cephalosporins. Keywords: Fluroquinolones, Cephalosporins, Multidrug resistant, ESBL, Amp C

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Mazzella, L. J., and R. F. Pratt. "Effect of the 3′-leaving group on turnover of cephem antibiotics by a class C β-lactamase." Biochemical Journal 259, no. 1 (April 1, 1989): 255–60. http://dx.doi.org/10.1042/bj2590255.

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It has been previously demonstrated for class A beta-lactamases and the DD-peptidase of Streptomyces R61 that the presence of a leaving group at the 3′-position of a cephalosporin can lead to the generation of more-inert acyl-enzyme intermediates than from cephalosporins lacking such a leaving group, and thus to beta-lactamase inhibitors and potentially better antibiotics. In the present work we extend this result to a class C beta-lactamase, that of Enterobacter cloacae P99. The effect is not seen with first-generation cephalosporins, since here deacylation generally seems faster than elimination of the leaving group, but it does clearly appear with cephamycins and third-generation cephalosporins. The structural and/or mechanistic features of the active site giving rise to this phenomenon may thus be common to all serine beta-lactamases and transpeptidases.

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Tian, Guo-Bao, Yi-Qi Jiang, Ying-Min Huang, Yun Qin, Lian-Qiang Feng, Xue-Fei Zhang, Hong-Yu Li, et al. "Characterization of CTX-M-140, a Variant of CTX-M-14 Extended-Spectrum β-Lactamase with Decreased Cephalosporin Hydrolytic Activity, from Cephalosporin-Resistant Proteus mirabilis." Antimicrobial Agents and Chemotherapy 60, no. 10 (August 1, 2016): 6121–26. http://dx.doi.org/10.1128/aac.00822-16.

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ABSTRACTCTX-M-140, a novel CTX-M-type extended-spectrum β-lactamase (ESBL), was identified in cephalosporin-resistant clinical isolates ofProteus mirabilis. CTX-M-140 contained an alanine-to-threonine substitution at position 109 compared to its putative progenitor, CTX-M-14. When it was expressed in anEscherichia coliisogenic background, CTX-M-140 conferred 4- to 32-fold lower MICs of cephalosporins than those with CTX-M-14, indicating that the phenotype was attributable to this single substitution. For four mutants of CTX-M-14 that were constructed by site-directed mutagenesis (A109E, A109D, A109K, and A109R mutants), MICs of cephalosporins were similar to those for theE. colihost strain, which suggested that the alanine at position 109 was essential for cephalosporin hydrolysis. The kinetic properties of native CTX-M-14 and CTX-M-140 were consistent with the MICs for theE. coliclones. Compared with that of CTX-M-14, a lower hydrolytic activity against cephalosporins was observed for CTX-M-140.blaCTX-M-140is located on the chromosome as determined by I-CeuI pulsed-field gel electrophoresis (I-CeuI-PFGE) and Southern hybridization. The genetic environment surroundingblaCTX-M-140is identical to the sequence found in different plasmids withblaCTX-M-9-groupgenes among theEnterobacteriaceae. Genome sequencing and analysis showed thatP. mirabilisstrains withblaCTX-M-140have a genome size of ∼4 Mbp, with a GC content of 38.7% and 23 putative antibiotic resistance genes. Our results indicate that alanine at position 109 is critical for the hydrolytic activity of CTX-M-14 against oxyimino-cephalosporins.

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&NA;. "Cephalosporins." Reactions Weekly &NA;, no. 1194-1195 (March 2008): 12–13. http://dx.doi.org/10.2165/00128415-200811940-00037.

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&NA;. "Cephalosporins." Reactions Weekly &NA;, no. 561 (July 1995): 6. http://dx.doi.org/10.2165/00128415-199505610-00011.

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&NA;. "Cephalosporins." Reactions Weekly &NA;, no. 1096 (April 2006): 8. http://dx.doi.org/10.2165/00128415-200610960-00024.

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Harrison, Christopher J., and Denise Bratcher. "Cephalosporins." Pediatrics In Review 29, no. 8 (August 1, 2008): 264–73. http://dx.doi.org/10.1542/pir.29.8.264.

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Martens, Mark G. "Cephalosporins." Obstetrics and Gynecology Clinics of North America 16, no. 2 (June 1989): 291–304. http://dx.doi.org/10.1016/s0889-8545(21)00158-3.

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&NA;. "Cephalosporins." Drugs & Therapy Perspectives 3, no. 9 (May 1994): 13–14. http://dx.doi.org/10.2165/00042310-199403090-00006.

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&NA;. "Cephalosporins." Reactions Weekly &NA;, no. 1288 (February 2010): 11–12. http://dx.doi.org/10.2165/00128415-201012880-00030.

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Mevorach, or, Izidore S. Lossos, and Ran Oren. "Cefuroxime-Induced Fever." Annals of Pharmacotherapy 27, no. 7-8 (July 1993): 881–82. http://dx.doi.org/10.1177/106002809302700712.

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OBJECTIVE: To report on three patients with cefuroxime-induced fever. CASE SUMMARIES: Recurrence of fever was noted in three patients after five to seven days of cefuroxime sodium therapy for acute exacerbation of chronic obstructive pulmonary disease. No source of infection was found and the fevers resolved within 30 hours of drug discontinuation. One patient was rechallenged; the same pattern of fever resulted. DISCUSSION: Fever secondary to cephalosporin administration is reviewed and the place of cephalosporins in the differential diagnosis of fever is postulated. CONCLUSIONS: Cefuroxime should be added to the list of cephalosporins that induce fever.

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John, Shinu Mary, Bijoy Kumar Panda, J. K. Banerjee, and Nikki Soman. "A study on prescribing pattern of cephalosporins utilization and its compliance towards the hospital antibiotic policy in surgery ward of a tertiary care teaching hospital in India." International Surgery Journal 6, no. 10 (September 26, 2019): 3614. http://dx.doi.org/10.18203/2349-2902.isj20194413.

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Background: Extensive use of antibiotics is prevalent throughout India, and this is a matter of serious concern. There are several reports linking antibiotic usage to resistance. Towards addressing this problem, assessment of current prescribing pattern of antibiotics needs to be undertaken to monitor its appropriate use. This study was meant to assess the utilization of cephalosporins and its compliance towards the hospital antibiotic policy in surgery ward of a tertiary care teaching hospital.Methods: A prospective observational study was conducted with 250 inpatients of surgery ward. The demographic details, lab investigations, clinical diagnosis and current treatment were noted. The collected data was analysed for utilization of cephalosporin using World Health Organization (WHO) core prescribing indicators and defined daily dose per 100 bed-days. The hospital antibiotic policy was used as a benchmark for analyzing compliance of therapy.Results: Out of 250 patients, 69% was male and 31.2% was female population with mean age of 42.12±17.33 years. Majority of cases were clean-contaminated (36%) followed by clean (30.4%) and contaminated (17.6%) wounds. The average number of overall antibiotics and cephalosporins per encounter was 2.1 and 1 respectively. Among the total parenteral antibiotics, 63.9% were cephalosporins. Cephalosporins utilization was 2.68 DDD per 100 bed-days. Compliance with all the stated criteria was observed only in 124 (49.6%) patients.Conclusions: The rate of prescribing of cephalosporins has increased evidently which may result in the occurrence of bacterial resistance. A suboptimal rate of compliance recommends a strict monitoring in the usage of cephalosporins with periodical updation of policy.

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Lau, A. H., K. Pyle, N. O. Kronfol, and C. R. Libertin. "Removal of Cephalosporins by Continuous Arteriovenous Ultrafiltration (CAVU) and Hemofiltration (CAVH)." International Journal of Artificial Organs 12, no. 6 (June 1989): 379–83. http://dx.doi.org/10.1177/039139888901200606.

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Cephalosporins are used with increasing frequency for sepsis treatment in patients receiving CAVU and CAVH. The different cephalosporins share the same basic molecular structure, yet they exhibit varied extent of plasma protein binding. Different amounts of the antibiotics may be removed by the ultrafiltration procedure because of these variations of physicochemical properties. We evaluated the sieving of eight new cephalosporins across the hemofilter membrane using an in vitro model. Bovine blood was perfused through polysulfone membranes at blood and ultrafiltrate flow rates of 100 and 20 ml/min respectively. Arterial plasma, venous plasma and ultrafiltrate drug concentrations were used to determine sieving coefficients. The sieving coefficients correlated well with the ultrafiltrate-arterial plasma drug concentration ratio (r= 0.679 - 0.972) but poorly with the extent of protein binding. Factors other than protein binding may therefore affect the drug sieving. Based on the findings, it was predicted that 0.2 - 21.9% of the daily cephalosporin dose may be removed by the CAVU and CAVH treatment. The need to alter drug dosages depends on the techniques of the ultrafiltration and hemofiltration procedure, the kinetics of the cephalosporins in patients, the sensitivity of the pathogen and the nature of the infection.

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Phan, Minh-Duy, Amy L. Bottomley, Kate M. Peters, Elizabeth J. Harry, and Mark A. Schembri. "Uncovering novel susceptibility targets to enhance the efficacy of third-generation cephalosporins against ESBL-producing uropathogenic Escherichia coli." Journal of Antimicrobial Chemotherapy 75, no. 6 (February 19, 2020): 1415–23. http://dx.doi.org/10.1093/jac/dkaa023.

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Abstract Background Uropathogenic Escherichia coli (UPEC) are a major cause of urinary tract infection (UTI), one of the most common infectious diseases in humans. UPEC are increasingly associated with resistance to multiple antibiotics. This includes resistance to third-generation cephalosporins, a common class of antibiotics frequently used to treat UTI. Methods We employed a high-throughput genome-wide screen using saturated transposon mutagenesis and transposon directed insertion-site sequencing (TraDIS) together with phenotypic resistance assessment to identify key genes required for survival of the MDR UPEC ST131 strain EC958 in the presence of the third-generation cephalosporin cefotaxime. Results We showed that blaCMY-23 is the major ESBL gene in EC958 responsible for mediating resistance to cefotaxime. Our screen also revealed that mutation of genes involved in cell division and the twin-arginine translocation pathway sensitized EC958 to cefotaxime. The role of these cell-division and protein-secretion genes in cefotaxime resistance was confirmed through the construction of mutants and phenotypic testing. Mutation of these genes also sensitized EC958 to other cephalosporins. Conclusions This work provides an exemplar for the application of TraDIS to define molecular mechanisms of resistance to antibiotics. The identification of mutants that sensitize UPEC to cefotaxime, despite the presence of a cephalosporinase, provides a framework for the development of new approaches to treat infections caused by MDR pathogens.

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Siemieniuk, Reed, Yung Lee, Isaac Bogoch, Romina Brignardello-Petersen, Yutong Fei, Paul Alexander, Theresa Aves, et al. "747. Antibiotic Therapy for Community-Acquired Pneumonia: A Systematic Review and Network Meta-Analysis of Randomized Trials." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S268. http://dx.doi.org/10.1093/ofid/ofy210.754.

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Abstract Background Community-acquired pneumonia (CAP) is one of the top causes of life-years lost globally. The optimal empiric antibiotic therapy regimen is uncertain. Randomized controlled trials (RCTs) provide useful information about relative antibiotic effectiveness. Methods We systematically searched Medline, EMBASE, and CENTRAL for RCTs comparing at least two empiric antibiotic regimens in patients with CAP, to March 17, 2017. We performed a systematic review and network meta-analysis and network meta-regression using a Bayesian framework. We used GRADE to assess certainty in the effect estimates. Results From 18,056 citations, we included 303 RCTs. Most studies (69.9%) were not blinded. All networks had low global heterogeneity (I2 0%). There were 26,423 participants included in the analysis of mortality and 30,559 for treatment failure. Seven hundred and twenty-six (2.9%) participants died. Patients randomized to third generation cephalosporins alone had higher mortality than those randomized to early generation fluoroquinolones (risk ratio [RR] 2.08, 95% credible interval 1.17–3.90), later generation fluoroquinolones (RR 2.32, 1.44–4.26), and cephalosporin-fluoroquinolone combinations (RR 3.21, 0.99–12.49). Participants who were randomized to a cephalosporin plus macrolide were less likely to die than those who received a third generation cephalosporin alone (RR 0.47, 0.21–0.99). The evidence was similar for treatment failure. Β-lactam plus β-lactamase inhibitors (e.g., piperacillin–tazobactam), early generation cephalosporins, and daptomycin appeared to confer a higher risk of mortality and/or treatment failure than most other antibiotic regimens including third-generation cephalosporins alone. For key comparisons, the GRADE quality of evidence was low or moderate. Conclusion In patients with CAP, an antibiotic regimen that includes a fluoroquinolone (and possibly a macrolide) may reduce mortality by ~1–2% compared with β-lactams (with or without a β-lactamase inhibitor) and cephalosporins alone. High quality, blinded and pragmatic randomized evidence would be helpful to increase certainty in the evidence. Disclosures All authors: No reported disclosures.

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Rhyou, Hyo-In, Young-Hee Nam, Su-Chin Kim, Go-Eun Doo, Chae-Yeon Ha, Hee-Joo Nam, Sung-Dae Woo, et al. "Cefaclor-induced hypersensitivity: Differences in the incidence of anaphylaxis relative to other 2nd and 3rd generation cephalosporins." PLOS ONE 16, no. 7 (July 22, 2021): e0254898. http://dx.doi.org/10.1371/journal.pone.0254898.

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Cefaclor, a second-generation oral cephalosporin, is the most frequently prescribed cephalosporin in Korea. Studies, however, have yet to analyze the incidence of cefaclor-associated adverse drug reactions (ADRs), including hypersensitivity (HS), according to total national usage rates. This study aimed to investigate the incidence rates and clinical features of cefaclor ADRs reported to the Korean Adverse Event Reporting System (KAERS) and Health Insurance Review and Assessment Service (HIRA) database for the most recent 5 years. Reviewing the HIRA database, which contains information on all insurance claims, including prescribed medications and patient demographics, we identified the total number of individuals who had been prescribed cefaclor and other cephalosporins including 2nd generation without cefaclor and 3rd generation antibiotics from January 2014 to December 2018. Additionally, we retrospectively analyzed all ADRs reported to the KAERS for these drugs over the same study period. Incidence rates for ADRs, HS, and anaphylaxis to cefaclor were 1.92/10,000 persons, 1.17/10,000 persons, and 0.38/10,000 persons, respectively, lower than those to other 2nd and 3rd cephalosporins. Among all ADRs, HS (60.9% vs. 43.6% vs. 44.8%, P <0.001) and anaphylaxis (19.8% vs. 4.6% vs. 4.7%, P <0.001) were more common for cefaclor than for other 2nd and 3rd cephalosporins. Females, individuals under 65 years of age, concomitant use of drugs, and serious ADRs were more strongly associated with HS to cefaclor than with HS to other 2nd and 3rd cephalosporins. In a nationwide database for the Korean population, the incidence of cefaclor-induced ADRs, particularly HS and anaphylaxis, was high. Female sex, age younger than 65 years, and concomitant use of drugs may be associated with HS to cefaclor.

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Lai, Chen, Lu, Lin, Chen, Su, Chao, Chuang, and Tang. "The Potential Role of Sulbactam and Cephalosporins Plus Daptomycin Against Daptomycin-Nonsusceptible VISA and H-VISA Isolates: An in Vitro Study." Antibiotics 8, no. 4 (October 14, 2019): 184. http://dx.doi.org/10.3390/antibiotics8040184.

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This study assesses the synergistic effect of the combination of cephalosporins and sulbactam with daptomycin against daptomycin-nonsusceptible, vancomycin-intermediate resistant Staphylococcus aureus (VISA) or heterogeneous vancomycin-intermediate S. aureus (h-VISA) isolates. The in vitro activity of daptomycin against daptomycin-nonsusceptible VISA/h-VISA isolates after adding cephalosporins with or without sulbactam was evaluated. The MIC of daptomycin against the VISA/h-VISA isolates was reduced after adding cephalosporins to daptomycin. Except for one VISA and two h-VISA isolates, the other VISA/h-VISA isolates became daptomycin-susceptible (MICs 1 mg/L). After adding sulbactam to each daptomycin/cephalosporin combination, the MIC of daptomycin against the VISA/h-VISA isolates decreased for 5 (33.3%), 6 (40.0%), 6 (40.0%), and 6 (40.0%) isolates with the cefazolin, cefmetazole, cefotaxime, and cefepime combinations, respectively. Synergism using the checkerboard method was noted in 100% of cefazolin and cefotaxime combinations and 87% and 80% of cefmetazole and cefepime combinations for all the VISA and h-VISA isolates. With the addition of sulbactam, synergism was noted in 100% of cefazolin, cefmetazole, and cefotaxime combinations and 93% of the cefepime combinations for all the VISA and h-VISA isolates. Almost all the FICs for the three-drug combinations were lower than those for the two-drug combinations. Using time-killing methods, a synergistic effect against five h-VISA isolates was observed. A synergistic effect of daptomycin, sulbactam, and each cephalosporin was observed for all VISA isolates. In conclusion, the activity of daptomycin against daptomycin-nonsusceptible VISA/h-VISA isolates can be enhanced by adding cephalosporins, and partially further promoted by sulbactam.

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Smith, Robert G. "Penicillin and Cephalosporin Drug Allergies." Journal of the American Podiatric Medical Association 98, no. 6 (November 1, 2008): 479–88. http://dx.doi.org/10.7547/0980479.

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Medication hypersensitivity is a constant variable that podiatric physicians face during their professional day. To avoid potential patient harm, an understanding of penicillin and cephalosporin hypersensitivities as it pertains to podiatric medicine needs to be achieved. To accomplish this, a narrative describing the signs, symptoms, and immunologic mechanisms for the basis of penicillin and cephalosporin drug hypersensitivities is presented. Second, specific medical literature serving as clinical-based evidence to support the prescribing of cephalosporins in patients with documented penicillin allergy is presented. Finally, a review of the medical and legal literature describing health-care provider liability regarding subsequent drug hypersensitivity is presented. The information contained in this review allows for the evolving paradigm that permits the prescribing of selective cephalosporins to patients with a history of penicillin allergy as long as the allergic symptoms were not serious or life-threatening. (J Am Podiatr Med Assoc 98(6): 479–488, 2008)

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Weinstein, Robert A. "Endemic Emergence of Cephalosporin-Resistant Enterobacter: Relation to Prior Therapy." Infection Control & Hospital Epidemiology 7, S2 (February 1986): 120–23. http://dx.doi.org/10.1017/s0195941700065632.

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The “second” and “third” generation cephalosporins offer striking antimicrobial activity against a wide spectrum of Enterobacteriaceae. Nevertheless, mutants resistant to these drugs have emerged in both laboratory and clinical settings. For example, before the commercial availability of the third-generation agents, we treated three cardiac surgery patients for Enterobacter mediastinitis with aminoglycosides and high doses of cefamandole. In two, initial treatment failed due to emergence of strains that were not only resistant to cefamandole, but also to then experimental third-generation drugs. Despite such reports and in vitro studies of the mechanisms of resistance, the frequency with which broad-spectrum cephalosporin resistance develops in clinical practice is not clear. To help delineate this problem, we have reviewed our hospital's experience with Enterobacter strains resistant to newer cephalosporins (using cefamandole and cefotaxime as prototypes) and the relation of resistant strains to cephalosporin use, with special attention to our cardiac surgery patients.

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Ting, Susan. "Reverse-Phase Liquid Chromatographic Analysis of Cephalosporins." Journal of AOAC INTERNATIONAL 71, no. 6 (November 1, 1988): 1123–30. http://dx.doi.org/10.1093/jaoac/71.6.1123.

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Abstract A simple and rapid reverse-phase liquid chromatographic method was developed for the qualitative and quantitative analysis of 13 cephalosporin compounds. A mixture of cefaclor, cefadroxil, cefamandole nafate, cefamandole sodium, cefazolin, cefoperazone, cefotaxime, cefoxitin, ceftizoxime, cephalothin, cephalexin, cephapirin, and cephradine was resolved into its components in raw material and dosage form samples by using a Clg column, a methanol-water-acetic acid (30 + 70 + 0.1) mobile phase, and a UV detector set at 254 nm. The proposed method is suited both for the determination of cephalosporins in a wide variety of commercial dosage forms and for the investigation of related compounds and other impurities in samples of 7 of the cephalosporins

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D’Errico, Stefano, Paola Frati, Martina Zanon, Eleonora Valentinuz, Federico Manetti, Matteo Scopetti, Alessandro Santurro, and Vittorio Fineschi. "Cephalosporins’ Cross-Reactivity and the High Degree of Required Knowledge. Case Report and Review of the Literature." Antibiotics 9, no. 5 (April 25, 2020): 209. http://dx.doi.org/10.3390/antibiotics9050209.

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Antibiotic cross-reactivity represents a phenomenon of considerable interest as well as antibiotic resistance. Immediate reactions to cephalosporins are reported in the literature with a prevalence of only 1–3% of the population, while anaphylactic reactions are rarely described (approximately 0.0001–0.1%) as well as fatalities. Allergic reaction to cephalosporins may occur because of sensitization to unique cephalosporin haptens or to determinants shared with penicillins. Cross-reactivity between cephalosporins represents, in fact, a well-known threatening event involving cephalosporins with similar or identical R1- or R2-side chains. The present report describes the case of a 79-year-old man who suddenly died after intramuscular administration of ceftriaxone. Serum dosage of mast cell tryptase from a femoral blood sample at 3 and 24 h detected values of 87.7μg/L and 93.5μg/L, respectively (cut-off value 44.3 μg/L); the serum-specific IgE for penicillins, amoxicillin, cephaclor and also for the most common allergens were also determined. A complete post-mortem examination was performed, including gross, histological and immunohistochemical examination, with an anti-tryptase antibody. The cause of death was identified as anaphylactic shock: past administrations of cefepime sensitized the subject to cephalosporins and a fatal cross-reactivity of ceftriaxone with cefepime occurred due to the identical seven-position side chain structure in both molecules. The reported case offers food for thought regarding the study of cross-reactivity and the need to clarify the predictability and preventability of the phenomenon in fatal events.

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Sonawane, Vijay Chintaman. "Enzymatic Modifications of Cephalosporins by Cephalosporin Acylase and Other Enzymes." Critical Reviews in Biotechnology 26, no. 2 (January 2006): 95–120. http://dx.doi.org/10.1080/07388550600718630.

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ALBRECHT, H. A., G. BESKID, J. G. CHRISTENSON, J. W. DURKIN, V. FALLAT, N. H. GEORGOPAPADAKOU, D. D. KEITH, et al. "ChemInform Abstract: Dual-Action Cephalosporins: Cephalosporin 3′-Quaternary Ammonium Quinolones." ChemInform 22, no. 38 (August 22, 2010): no. http://dx.doi.org/10.1002/chin.199138275.

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Journal articles on the topic 'Cephalosporins'

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