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1
Winkler, Heinz, and Peter Haiden. "Allograft Bone as Antibiotic Carrier." Journal of Bone and Joint Infection 2, no. 1 (January 1, 2017): 52–62. http://dx.doi.org/10.7150/jbji.17466.
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Abstract. The treatment of chronic bone and joint infections is characterized by obstinate persistency of the causing microorganisms and resulting long term disability to patients, associated with remarkable costs for the health care system. Difficulties derive from biofilm formed on dead bone and eventual implants, with resistance against immunological defences and antimicrobial substances. Biofilm embedded bacteria require up to 1000 times the antibiotic concentration of planktonic bacteria for elimination. Systemic antibiotic treatment alone cannot provide the concentrations required and surgical intervention is always prerequisite for potentially providing a cure. A second issue is that osseous defects are almost always present after surgical debridement, and it is difficult to address their reconstruction. One option is to use bone grafts, either from the patient´s own body or from foreign donors (allografts). Grafts are usually unvascularized and are prone to colonization with bacteria. Loading of allografts with antibiotics may not only protect grafts from bacterial adhesion but, using appropriate processing methods, may also provide high local antibiotic concentrations that may eliminate remaining sessile pathogens. For efficient action as antibiotic carriers, the release of antibiotics should be above the minimum biofilm eradication concentration (MBEC) for a prolonged period of time. Cleaning the bone from bone marrow opens a large reservoir for storage of antimicrobial substances that, after implantation, may be released to the surrounding in a sustained mode, possibly eliminating remaining biofilm remnants. Removal of bone marrow, leaving a pure matrix, provides increased safety and improved revascularization of the graft. Local provision of antibiotic concentrations above the MBEC may enable simultaneous internal fixation with osteosynthetic material and single stage exchange of infected endoprostheses, resulting in shorter hospital stays with reduced pain and faster rehabilitation of patients.
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Coraça-Huber, Débora C., Stephan J. M. Steixner, Stevo Najman, Sanja Stojanovic, Ronja Finze, Denis Rimashevskiy, Dina Saginova, Mike Barbeck, and Reinhard Schnettler. "Lyophilized Human Bone Allograft as an Antibiotic Carrier: An In Vitro and In Vivo Study." Antibiotics 11, no. 7 (July 19, 2022): 969. http://dx.doi.org/10.3390/antibiotics11070969.
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Background: Antibiotics delivered from implanted bone substitute materials (BSM) can potentially be used to prevent acute infections and biofilm formation, providing high concentrations of antibiotics at the surgical site without systemic toxicity. In addition, BSM should allow osteoconductivity supporting bone healing without further surgery. Promising results have been achieved using lyophilized bone allografts mixed with antibiotics. Methods: In this study specially prepared human bone allografts were evaluated as an antibiotic carrier in vitro and in vivo. The efficacy of different antibiotic-impregnated bone allografts was measured by drug release tests in vitro and in vivo and bacterial susceptibility tests using four bacterial species usually responsible for implant-associated infections. Results: The loading procedures of allograft bone substitutes with antibiotics were successful. Some of the antibiotic concentrations exceeded the MIC90 for up to 7 days in vitro and for up to 72 h in vivo. The susceptibility tests showed that S. epidermidis ATCC 12228 was the most susceptible bacterial species in comparison to the other strains tested for all antibiotic substances. Vancomycin and rifampicin showed the best results against standard and patient-isolated strains in vitro. In vivo, new bone formation was comparable in all study groups including the control group without antibiotic loading. Conclusions: Human bone allografts showed the capacity to act as customized loaded antibiotic carriers to prevent acute infections and should be considered in the management of bone infections in combination with systemic antimicrobial therapy.
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Kotrange, Harshada, Agnieszka Najda, Aarti Bains, Robert Gruszecki, Prince Chawla, and Mansuri M. Tosif. "Metal and Metal Oxide Nanoparticle as a Novel Antibiotic Carrier for the Direct Delivery of Antibiotics." International Journal of Molecular Sciences 22, no. 17 (September 4, 2021): 9596. http://dx.doi.org/10.3390/ijms22179596.
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In addition to the benefits, increasing the constant need for antibiotics has resulted in the development of antibiotic bacterial resistance over time. Antibiotic tolerance mainly evolves in these bacteria through efflux pumps and biofilms. Leading to its modern and profitable uses, emerging nanotechnology is a significant field of research that is considered as the most important scientific breakthrough in recent years. Metal nanoparticles as nanocarriers are currently attracting a lot of interest from scientists, because of their wide range of applications and higher compatibility with bioactive components. As a consequence of their ability to inhibit the growth of bacteria, nanoparticles have been shown to have significant antibacterial, antifungal, antiviral, and antiparasitic efficacy in the battle against antibiotic resistance in microorganisms. As a result, this study covers bacterial tolerance to antibiotics, the antibacterial properties of various metal nanoparticles, their mechanisms, and the use of various metal and metal oxide nanoparticles as novel antibiotic carriers for direct antibiotic delivery.
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Witsø, Eivind, Leif Persen, Kirsti Løseth, Pål Benum, and Kåre Bergh. "Cancellous bone as an antibiotic carrier." Acta Orthopaedica Scandinavica 71, no. 1 (January 2000): 80–84. http://dx.doi.org/10.1080/00016470052943955.
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Ferguson, Jamie, Michael Diefenbeck, and Martin McNally. "Ceramic Biocomposites as Biodegradable Antibiotic Carriers in the Treatment of Bone Infections." Journal of Bone and Joint Infection 2, no. 1 (January 1, 2017): 38–51. http://dx.doi.org/10.7150/jbji.17234.
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Abstract. Local release of antibiotic has advantages in the treatment of chronic osteomyelitis and infected fractures. The adequacy of surgical debridement is still key to successful clearance of infection but local antibiotic carriers seem to afford greater success rates by targeting the residual organisms present after debridement and delivering much higher local antibiotic concentrations compared with systemic antibiotics alone. Biodegradable ceramic carriers can be used to fill osseous defects, which reduces the dead space and provides the potential for subsequent repair of the osseous defect as they dissolve away. A dissolving ceramic antibiotic carrier also raises the possibility of single stage surgery with definitive closure and avoids the need for subsequent surgery for spacer removal.In this article we provide an overview of the properties of various biodegradable ceramics, including calcium sulphate, the calcium orthophosphate ceramics, calcium phosphate cement and polyphasic carriers. We summarise the antibiotic elution properties as investigated in previous animal studies as well as the clinical outcomes from clinical research investigating their use in the surgical management of chronic osteomyelitis.Calcium sulphate pellets have been shown to be effective in treating local infection, although newer polyphasic carriers may support greater osseous repair and reduce the risk of further fracture or the need for secondary reconstructive surgery. The use of ceramic biocomposites to deliver antibiotics together with BMPs, bisphosphonates, growth factors or living cells is under investigation and merits further study.We propose a treatment protocol, based on the Cierny-Mader classification, to help guide the appropriate selection of a suitable ceramic antibiotic carrier in the surgical treatment of chronic osteomyelitis.
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Rasita, Yoeke Dewi, Kuntaman, and Kartuti Debora. "Description of Antibiotic Susceptibility Pattern Analysis on Methicillin-Susceptible Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus Clothing Gene Panton-Valentine Leukocidin from Clinic Isolate." Journal of Computational and Theoretical Nanoscience 17, no. 7 (July 1, 2020): 3085–91. http://dx.doi.org/10.1166/jctn.2020.9140.
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Staphylococcus aureus is the most common cause of health care acquired infection and has a high rate of morbidity and mortality. S. aureus has a number of virulent factors that facilitate these bacteria to adhesion to the tissues of the host, avoiding the body’s defense system, and damaging the host cell. PVL cytotoxin is one of the virulent factors that causes hypervirulent in S. aureus. The infections caused are varied, ranging from severe skin infections, peneumonia, and sepsis. To obtain a description of the antibiotic susceptibility pattern in Methicillin-sensitive Staphylococcus aureus (MSSA) and Methicillin-resistant Staphylococcus aureus (MRSA) carriers of the pvl gene that causes infection. Isolate S. aureus derived from clinical isolates of inpatients who have identified and tested phenotypic antibiotic susceptibility using BD Phoenix TM Automated Microbiology System or Vitek2 Compact bioMérieux system followed by genotypic testing using PCR to detect the presence of the pvl gene. Of 85 S. aureus isolates, 65 isolates (76.5%) included MSSA bacterial strains and 20 isolates (23.5%) including strains of MRSA bacteria. Of the 65 isolates of MSSA bacterial strains, 9 isolates (13.84%) had the pvl gene, and of the 20 isolates of the MRSA strain, 1 isolate (5%) had the pvl gene. The susceptibility of non betalactam antibiotics to MSSA virus strains of pvl gene carriers ranged from 77.8%-100%. MSSA bacterial strains that did not carry the pvl gene also showed a non-betallactam antibiotic susceptibility ranging from 69.1%-100%. The susceptibility of tetracycline antibiotics to both MSSA strains of both pvl and non-carriers of pvl genes was 55.6% and 39.3% respectively. There was no significant difference between the antibiotic susceptibility pattern in the MSSA carrier strain of the pvl gene carrier and the proportion of the MRSA carrier strain of the pvl gene carrier.
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Dzięcioł, M., W. Niżański, E. Stańczyk, R. Kozdrowski, L. Najder-Kozdrowska, and J. Twardoń. "The influence of antibiotic treatment of bitches in oestrus on their attractiveness to males during mating." Polish Journal of Veterinary Sciences 16, no. 3 (September 1, 2013): 509–16. http://dx.doi.org/10.2478/pjvs-2013-0071.
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Abstract The aim of this study was to evaluate the influence of the antibiotic treatment, including the mode of drugs administration, on bitches’ attractiveness to the stud dogs during mating. Moreover, we tried to estimate the possibility of aversive effect of the drug vehicle on the male behavior. In experiment I, four bitches in oestrus without antibiotic treatment (group A), four bitches treated with intravaginal antibiotic (group B) and four bitches treated with intramuscular antibiotic (group C) were presented to four stud dogs. In experiment II, bitches in oestrus (n=5) were presented to the males (n=2) before and after the application to the females’ vulva the antibiotic carrier - Miglyol 840 (Sasol, Germany). In both experiments the presence of the typical sexual behavior of the males (sniffing, licking the vulva and anal region, mating attempts) was evaluated. In experiment III the reaction of the males to the samples containing oestrual discharge from the bitches untreated and treated with antibiotics was evaluated. In the last part of study the aversion reaction to the samples containing antibiotic and the antibiotic carrier was evaluated. The results of experiments showed that females treated with the antibiotics were less attractive to males than untreated females, regardless of the method of administration. We did not observe adverse effect of the antibiotic carrier but samples from the bitches treated with antibiotics were significantly less attractive to the males. We concluded that the reason for reduced attractiveness of the bitches in oestrus after antibiotic treatment was the changes in semiochemical signal emitted by treated females as a consequence of elimination of the vaginal bacterial flora, which seems to be involved in creation of the typical, recognizable by the stud dogs, oestrual signal but also by the possible covering effect of used drugs.
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LACLAIR, J., T. FOLEY, T. SCHEGG, C. REGAN, and M. BURKART. "Manipulation of Carrier Proteins in Antibiotic Biosynthesis." Chemistry & Biology 11, no. 2 (February 2004): 195–201. http://dx.doi.org/10.1016/s1074-5521(04)00032-8.
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Marchianò, Verdiana, María Matos, Esther Serrano-Pertierra, Gemma Gutiérrez, and M. C. Blanco-López. "Vesicles as antibiotic carrier: State of art." International Journal of Pharmaceutics 585 (July 2020): 119478. http://dx.doi.org/10.1016/j.ijpharm.2020.119478.
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La Clair, James J., Timothy L. Foley, Tracy R. Schegg, Conor M. Regan, and Michael D. Burkart. "Manipulation of Carrier Proteins in Antibiotic Biosynthesis." Chemistry & Biology 11, no. 2 (February 2004): 195–201. http://dx.doi.org/10.1016/j.chembiol.2004.02.010.
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Karr, Jeffrey C., Joseph Lauretta, and Georgia Keriazes. "In Vitro Antimicrobial Activity of Calcium Sulfate and Hydroxyapatite (Cerament Bone Void Filler) Discs Using Heat-Sensitive and Non–Heat-sensitive Antibiotics Against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa." Journal of the American Podiatric Medical Association 101, no. 2 (March 1, 2011): 146–52. http://dx.doi.org/10.7547/1010146.
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Background: Several absorbable and nonabsorbable antibiotic carrier systems are available in the adjunctive surgical management of osteomyelitis of the foot, ankle, and lower leg. These carrier systems have significant limitations regarding which antibiotics can be successfully incorporated into the carrier vehicle. The calcium sulfate and hydroxyapatite Cerament Bone Void Filler is a biocompatible, absorbable ceramic bone void filler that can successfully deliver multiple heat-stable and heat-unstable antibiotics that have not been generally used before with antibiotic beads in treating musculoskeletal infections. Methods: Cerament Bone Void Filler discs with the antibiotics rifampin, vancomycin, tobramycin, cefazolin, cefepime hydrochloride, vancomycin-tobramycin, piperacillin-tazobactam, ceftazidime, and ticarcillin-clavulanate were tested in vitro against methicillin-resistant Staphylococcus aureus. Results: The zones of inhibition for the Cerament Bone Void Filler antibiotic discs plated against Staphylococcus aureus obtained were 33% to 222% greater than the minimum zones of inhibition breakpoints for bacteria susceptibility as defined by the standard set by the Clinical and Laboratory Standards Institute. Cerament Bone Void Filler discs with the antibiotics plated against Pseudomonas aeruginosa produced zones of inhibition of 93% to 200% greater than the minimum zones of inhibition breakpoints for bacteria susceptibility as defined by the standard set by the Clinical and Laboratory Standards Institute. Conclusions: The calcium sulfate and hydroxyapatite Cerament Bone Void Filler was an excellent carrier vehicle for multiple antibiotics creating in vitro significant zones of inhibition, thus demonstrating susceptibility against Staphylococcus aureus and Pseudomonas aeruginosa, which holds tremendous promise in treating osteomyeilits. (J Am Podiatr Med Assoc 101(2): 146–152, 2011)
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Anagnostakos, Konstantinos, and Katrin Schröder. "Antibiotic-Impregnated Bone Grafts in Orthopaedic and Trauma Surgery: A Systematic Review of the Literature." International Journal of Biomaterials 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/538061.
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There exist several options for local antibiotic therapy in orthopaedic and trauma surgery. Over the past years, the use of antibiotic-impregnated bone grafts (AIBGs) has become a popular procedure in the treatment of bone and joint infections. A major advantage of AIBGs involves the possibility of impregnation of various antibiotics depending on the sensitivity profile of the causative organism, whereas an additional surgery with removal of the antibiotic carrier is not necessary, as in the use of antibiotic-loaded bone cement. However, generalized conclusions cannot be clearly drawn from the existing literature due to differences of bone used, impregnation method, antibiotics, their doses, laboratory circumstances, or clinical indications. The present work reviews the literature regarding this topic and sheds some light onto the choice of bone and antibiotics, manufacturing details, and clinical experience.
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Steadman, William, Paul R. Chapman, Michael Schuetz, Beat Schmutz, Andrej Trampuz, and Kevin Tetsworth. "Local Antibiotic Delivery Options in Prosthetic Joint Infection." Antibiotics 12, no. 4 (April 14, 2023): 752. http://dx.doi.org/10.3390/antibiotics12040752.
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Prosthetic Joint Infection (PJI) causes significant morbidity and mortality for patients globally. Delivery of antibiotics to the site of infection has potential to improve the treatment outcomes and enhance biofilm eradication. These antibiotics can be delivered using an intra-articular catheter or combined with a carrier substance to enhance pharmacokinetic properties. Carrier options include non-resorbable polymethylmethacrylate (PMMA) bone cement and resorbable calcium sulphate, hydroxyapatite, bioactive glass, and hydrogels. PMMA allows for creation of structural spacers used in multi-stage revision procedures, however it requires subsequent removal and antibiotic compatibility and the levels delivered are variable. Calcium sulphate is the most researched resorbable carrier in PJI, but is associated with wound leakage and hypercalcaemia, and clinical evidence for its effectiveness remains at the early stage. Hydrogels provide a versatile combability with antibiotics and adjustable elution profiles, but clinical usage is currently limited. Novel anti-biofilm therapies include bacteriophages which have been used successfully in small case series.
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Coraça-Huber, Débora C., Christoph G. Ammann, Michael Nogler, Manfred Fille, Lars Frommelt, Klaus-Dieter Kühn, and Christian Fölsch. "Lyophilized allogeneic bone tissue as an antibiotic carrier." Cell and Tissue Banking 17, no. 4 (September 8, 2016): 629–42. http://dx.doi.org/10.1007/s10561-016-9582-5.
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Zhang, Lu, Ying Huang, Yang Zhou, Timothy Buckley, and Hua H. Wang. "Antibiotic Administration Routes Significantly Influence the Levels of Antibiotic Resistance in Gut Microbiota." Antimicrobial Agents and Chemotherapy 57, no. 8 (May 20, 2013): 3659–66. http://dx.doi.org/10.1128/aac.00670-13.
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ABSTRACTThis study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture oftet(M)-carryingEnterococcusspp. orblaCMY-2-carryingEscherichia coliwere treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection.
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Rotman, Stijn G., Thomas F. Moriarty, Benjamin Nottelet, Dirk W. Grijpma, David Eglin, and Olivier Guillaume. "Poly(Aspartic Acid) Functionalized Poly(ϵ-Caprolactone) Microspheres with Enhanced Hydroxyapatite Affinity as Bone Targeting Antibiotic Carriers." Pharmaceutics 12, no. 9 (September 17, 2020): 885. http://dx.doi.org/10.3390/pharmaceutics12090885.
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Bone infection is a feared complication for patients with surgically fixed bone fractures and local antibiotic delivery is important in prophylaxis and treatment of these infections. Recent studies indicated that Staphylococcus aureus can penetrate bone tissue through micron-sized canaliculi and evade systemic and currently available local antibiotic treatments. Targeting bacteria within the bone requires highly efficient delivery of antimicrobials to the infected bone tissue. In this work, a biodegradable microsphere carrier loaded with antibiotics and with specific affinity to bone mineral was developed. Two widely used antibiotics, i.e., Gentamicin-dioctyl sulfosuccinate (GM-AOT) and Ciprofloxacin (CF) were embedded in poly(ϵ-caprolactone) (PCL) microspheres fabricated by oil-in-water emulsion techniques with carboxylated poly(vinyl alcohol) (cPVA) as surfactant. The carboxylic acid groups present at the Poly(ϵ-caprolactone)/cPVA (PCL-cPVA) microsphere surface were functionalized with aspartic acid oligomers (ASP) granting bone targeting properties. We report on cPVA synthesis, microsphere formulation, and antibiotic loading of PCL/cPVA-ASP microspheres. Antibiotic loaded PCL/cPVA-ASP microspheres show sustained release of its antibiotic load and can inhibit bacterial growth in vitro for up to 6 days. PCL/cPVA-ASP microspheres show enhanced affinity to mineralized substrates compared to non-functionalized PCL/cPVA microspheres. These findings support further development of these bone targeting antibiotic carriers for potential treatment of persistent bone infections.
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Ahmed Azeem, Muhammad. "Antibiotic Resistance Profiling of Pseudomonas Species Isolated from Cloacal Swab of Domestic Pigeons." Lahore Garrison University Journal of Life Sciences 5, no. 3 (July 12, 2021): 155–63. http://dx.doi.org/10.54692/lgujls.2021.0503173.
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Antibiotics are used to treat a number of bacterial infections. However, overuse or misuse of antibiotics has raised serious concerns against antibioticresistance amongst bacteria. Hence, antibiotics are becoming inefficient in treating bacterial infections leading to an increase in mortality rate worldwide. The domestic animals especially birds are a major source of transmission of antibiotic resistant bacteria in human through excrement and cause bacterial diseases in human. The aim of the present study was to assess the efficacy of different antibiotics prior to their prescription as a measure to prevent antibiotic resistance in bacteria. For this 120 cloacal swab samples were collected from the domestic pigeons of District Narowal to isolate Pseudomonas sp. and assess the efficacy of different antibiotics prior to their prescription as a measure to prevent antibiotic resistance in bacteria. Antibacterial activities were evaluated by performing antibiotic susceptibility pattern of Pseudomonas isolates against 18 commercially available antibiotic discs [Trimethoprime (TMP), Clarithromycin (CLR), Gentamicin (GEN), Chloramphenicol (C), Ampicillin (AM), Streptomycin (S), Kanamycin (K), Nitrofurantoin (F), Amoxicillin (AX), Tazobactam (TPZ), Imipenem (IPM), Meropenem (MEM), Levofloxacin (LEV), Nalidixic acid (NA), Ceftriaxone (CRO), Amikacin (AK), Tetracycline (TE) and Ciprofloxacin (CIP)] by using Kirby-Bauer disc diffusion method. Amongst these antibiotics, notably Pseudomonas sp. showed highest sensitivity to Clarithromycin (93.94%), Ampicillin (100%), Amikacin (93%) and Nalidixic (100%). This study established a general antibiotic resistance pattern of commercially used different antibiotics for commonly encountered clinical isolates. Moreover, antibiotics susceptibility tests (AST) should be carried out prior to prescribing antibiotics to the patient. Additionally, the antibacterial activities of local clinical isolates and change in bacteriological profile due to indiscriminate use of antibiotics associated with appearance of multiple drug resistant strains should be evaluated. It was concluded that preventive measure and their implementation is quite necessary to control antibiotic resistance and domestic pigeons can be a carrier of Pseudomonas species and can transmit through their fecal material to humans and other animals.
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Eriksen, N. H. Riewerts, F. Espersen, V. Thamdrup Rosdahl, and K. Jensen. "Carriage ofStaphylococcus aureusamong 104 healthy persons during a 19-month period." Epidemiology and Infection 115, no. 1 (August 1995): 51–60. http://dx.doi.org/10.1017/s0950268800058118.
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SummaryThe present study was undertaken to investigate the frequency of the nasal carrier rate ofStaphylococcus aureus. The investigation was performed on 104 healthy persons. The total number of swabs performed was 1498 and this resulted in isolation of 522S. aureusstrains. All strains have been identified, tested for antibiotic susceptibility, and phage-typed. The carrier-index (number of positive swabs/number of total swabs for each individual person) was compared with different sampling and culturing methods, phage type, age, and resistance to antibiotics. There was statistical difference in carrier rate according to sex (P·05). Among the 104 persons 15 (14·4%) were persistent carriers, 17 (16·3%) intermittent carriers, 55 (52·9%) occasional carriers and 17 (16·3%) non-carriers. Among intermittent and occasional carriers the phage-type distribution was different from theS. aureusstrains isolated from Danish hospitalized patients in 1992, while the persistent carriers had similar phage-type distribution.
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Su, Wen-Yu, Yu-Chun Chen, and Feng-Huei Lin. "A New Type of Biphasic Calcium Phosphate Cement as a Gentamicin Carrier for Osteomyelitis." Evidence-Based Complementary and Alternative Medicine 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/801374.
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Osteomyelitis therapy is a long-term and inconvenient procedure for a patient. Antibiotic-loaded bone cements are both a complementary and alternative treatment option to intravenous antibiotic therapy for the treatment of osteomyelitis. In the current study, the biphasic calcium phosphate cement (CPC), calledα-TCP/HAP (α-tricalcium phosphate/hydroxyapatite) biphasic cement, was prepared as an antibiotics carrier for osteomyelitis. The developed biphasic cement with a microstructure ofα-TCP surrounding the HAP has a fast setting time which will fulfill the clinical demand. The X-ray diffraction and Fourier transform infrared spectrometry analyses showed the final phase to be HAP, the basic bone mineral, after setting for a period of time. Scanning electron microscopy revealed a porous structure with particle sizes of a few micrometers. The addition of gentamicin inα-TCP/HAP would delay the transition ofα-TCP but would not change the final-phase HAP. The gentamicin-loadedα-TCP/HAP supplies high doses of the antibiotic during the initial 24 hours when they are soaked in phosphate buffer solution (PBS). Thereafter, a slower drug release is produced, supplying minimum inhibitory concentration until the end of the experiment (30 days). Studies of growth inhibition ofStaphylococcus aureusandPseudomonas aeruginosain culture indicated that gentamicin released after 30 days fromα-TCP/HAP biphasic cement retained antibacterial activity.
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Flores, Michael J., Kelsey E. Brown, Saam Morshed, and David W. Shearer. "Evidence for Local Antibiotics in the Prevention of Infection in Orthopaedic Trauma." Journal of Clinical Medicine 11, no. 24 (December 16, 2022): 7461. http://dx.doi.org/10.3390/jcm11247461.
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Prevention of fracture-related infection (FRI) remains a substantial challenge in orthopaedic trauma care. There is evolving evidence to support the use of local antibiotics for both the prevention and treatment of musculoskeletal infection. Local antibiotics can achieve higher local tissue concentrations with a lower risk of systemic complications compared to intravenously administered antibiotics. These antibiotics may be administered in powder or liquid form without carrier, or if sustained release is desired, using a carrier. Polymethylmethacrylate (PMMA), ceramics, and hydrogels are examples of antibiotic carriers. Unlike PMMA, ceramics and hydrogels have the advantage of not requiring a second surgery for removal. The VANCO trial supported the use of powdered vancomycin in high-risk fracture cases for the reduction of Gram-positive infections; although, data is limited. Future studies will evaluate the use of aminoglycoside antibiotics to address Gram-negative infection prevention. While theoretical concerns exist with the use of local antibiotics, available studies suggest local antibiotics are safe with a low-risk of adverse effects.
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Colding-Rasmussen, Thomas, Peter Horstmann, Michael Mørk Petersen, and Werner Hettwer. "Antibiotic Elution Characteristics and Pharmacokinetics of Gentamicin and Vancomycin from a Mineral Antibiotic Carrier: An in vivo Evaluation of 32 Clinical Cases." Journal of Bone and Joint Infection 3, no. 4 (October 20, 2018): 234–40. http://dx.doi.org/10.7150/jbji.26301.
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Abstract. Introduction: Locally implanted antibiotic-eluting carriers may be a valuable adjuvant to the management of prosthetic joint infections. Aim: to assess local and plasma antibiotic concentrations as well as cumulative antibiotic urine excretion associated with clinical use of a gentamicin - or vancomycin-loaded mineral composite antibiotic carrier.Methods: 32 patients (male/female=19/13, mean age=56; 21-82 years) were prospectively followed after implantation of gentamicin (n=11), vancomycin (n=15), or a combination (n=7), using an antibiotic carrier (CERAMENT™|G or CERAMENT™|V, mean amount 11 (3-20) mL) during resection arthroplasty of the hip/knee. We measured antibiotic concentrations in plasma (1h, 3h, 24h, 48h and 72h post-implantation), urine (24h, 48h and 72h post-implantation) and in drain (n=15).Results: We observed low antibiotic concentrations in plasma (Gentamicin: 0.33 mg/L (95%-CI: 0.25-0.44) and vancomycin: 1.33 mg/L (95%-CI: 1.02-1.66)) and high concentrations in drain (Gentamicin: mean 57.8 mg/L (95%-CI: 45.8-69.7) and vancomycin: mean 234.4 mg/L (95%-CI: 198.9-269.7)). Use of a drain was associated with a statistically significant reduction in vancomycin urine excretion (55.6% (95% CI: 36.45-74.92) to 28.71% (95% CI: 13.07-44.35), p=0.042). A similar trend was observed for gentamicin (34.17% (95% CI: 24.62-43.72) to 16.22% (95% CI: 0-33.86), p=0.078).Conclusions: CERAMENT™G/V was associated with safe plasma concentrations and high local concentrations above minimum inhibitory concentration. Installation of a surgical drain results in removal of a substantial amount of antibiotics and reduces antibiotic urine excretion.
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Engin, Ayse Basak, and Atilla Engin. "Nanoantibiotics: A Novel Rational Approach to Antibiotic Resistant Infections." Current Drug Metabolism 20, no. 9 (October 4, 2019): 720–41. http://dx.doi.org/10.2174/1389200220666190806142835.
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Background: The main drawbacks for using conventional antimicrobial agents are the development of multiple drug resistance due to the use of high concentrations of antibiotics for extended periods. This vicious cycle often generates complications of persistent infections, and intolerable antibiotic toxicity. The problem is that while all new discovered antimicrobials are effective and promising, they remain as only short-term solutions to the overall challenge of drug-resistant bacteria. Objective: Recently, nanoantibiotics (nAbts) have been of tremendous interest in overcoming the drug resistance developed by several pathogenic microorganisms against most of the commonly used antibiotics. Compared with free antibiotic at the same concentration, drug delivered via a nanoparticle carrier has a much more prominent inhibitory effect on bacterial growth, and drug toxicity, along with prolonged drug release. Additionally, multiple drugs or antimicrobials can be packaged within the same smart polymer which can be designed with stimuli-responsive linkers. These stimuli-responsive nAbts open up the possibility of creating multipurpose and targeted antimicrobials. Biofilm formation still remains the leading cause of conventional antibiotic treatment failure. In contrast to conventional antibiotics nAbts easily penetrate into the biofilm, and selectively target biofilm matrix constituents through the introduction of bacteria specific ligands. In this context, various nanoparticles can be stabilized and functionalized with conventional antibiotics. These composites have a largely enhanced bactericidal efficiency compared to the free antibiotic. Conclusion: Nanoparticle-based carriers deliver antibiotics with better biofilm penetration and lower toxicity, thus combating bacterial resistance. However, the successful adaptation of nanoformulations to clinical practice involves a detailed assessment of their safety profiles and potential immunotoxicity.
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Zlotnikov, Igor D., Maria P. Davydova, Milan R. Danilov, Sergey S. Krylov, Natalya G. Belogurova, and Elena V. Kudryashova. "Covalent Conjugates of Allylbenzenes and Terpenoids as Antibiotics Enhancers with the Function of Prolonged Action." Pharmaceuticals 16, no. 8 (August 4, 2023): 1102. http://dx.doi.org/10.3390/ph16081102.
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The drug resistance of pathogenic bacteria is often due efflux pumps—specific proteins that remove foreign compounds from bacterial cells. To overcome drug resistance, adjuvants are often used that can inhibit efflux pumps or other systems that ensure the resistance of bacteria to the action of antibiotics. We assumed that a new level of effectiveness with the use of an antibiotic + an adjuvant pair could be achieved by their joint delivery into the pathogen. To test this hypothesis, we constructed a series of molecular carriers based on poly-(olygo-, dendry)mers based on cyclodextrin-grafted PEI or mannan, as well as glycol chitosan, covalently bound to antibiotic, adjuvant, and the oligosaccharide ligand to the macrophage mannose receptor (CD206), which we studied earlier and showed high efficiency and selectivity of delivery of a therapeutic “cargo” to macrophages. Moxifloxacin was used as an antibiotic, and terpenoid and allylbenzene compounds were used as adjuvants, for which we previously discovered the ability to inhibit bacterial efflux pumps. We show that: (a) the resulting structures were stable in vitro for a long time (up to 10 days); (b) they were adsorbed on bacterial cells, providing a local increase in the concentration of the antibiotic and adjuvant in pathogen cells; (c) they were internalized by bacterial cells, ensuring the accumulation of both antibiotic and adjuvant inside bacterial cells; (d) the adjuvant, after entering the bacterial cell, provided inhibition of the efflux pumps; (e) due to this action of the adjuvant, combined with the targeted delivery by the carrier, the antibiotic’s half-life in rats increased by more than 2 times, the effective concentration of the drug in the blood plasma (AUC) increased up to 8–10 times; (f) a significant increase in the effectiveness of the antibacterial action against Gram+ and Gram- cells was achieved (up to 3 times). Potentially, such an approach would significantly increase the effectiveness of therapies for a number of infectious and other diseases, reduce the dosage of antibiotics, shorten the duration of treatment, and reduce the risk of developing bacterial resistance. Moreover, the use of a polymer carrier with covalently bound organic molecules of different structures will avoid problems linked to different (suboptimal) solubility and bio-distribution of the administered molecules, which would be almost inevitable when using the same compounds separately. It would be very difficult to find antibiotic/adjuvant pairs that simultaneously achieve optimal concentrations in the same target cells. In our case, terpenoids and alkylbenzenes used as adjuvants are practically insoluble as individual compounds, and their unacceptable pharmacological properties would not allow them to be used as efflux pump inhibitors.
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Reinisch, Katharina, Michel Schläppi, Christoph Meier, and Peter Wahl. "Local antibiotic treatment with calcium sulfate as carrier material improves the outcome of debridement, antibiotics, and implant retention procedures for periprosthetic joint infections after hip arthroplasty – a retrospective study." Journal of Bone and Joint Infection 7, no. 1 (January 20, 2022): 11–21. http://dx.doi.org/10.5194/jbji-7-11-2022.
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Abstract. Purpose: Debridement, antibiotics, and implant retention (DAIR) is an established treatment modality in periprosthetic joint infections (PJIs), but success rates vary. This study compared the success of DAIR for PJIs after a total hip arthroplasty (THA), with or without local antibiotic delivery with CaSO4 as the carrier material. Methods: A retrospective review of DAIR for PJIs after THA performed between 2010 and 2018, including 41 patients is conducted. A total of 27 patients were treated by DAIR with local antibiotics with CaSO4 as the carrier material, and 14 patients were treated by a standard DAIR. The endpoints were treatment failure, defined as the need for a reoperation, either a second DAIR or a prosthesis removal or exchange due to persistent or recurrent infection, the initiation of a long-term suppressive antibiotic treatment, or death related to infection. Results: Considering any reoperation as an outcome, 11 of 14 cases treated without AB-CaSO4 (79 %) and 4 of the 27 cases treated with AB-CaSO4 failed (15 %). Considering revision as an outcome, 9 out of 14 cases treated without AB-CaSO4 (64 %) and 4 of the 27 cases treated with AB-CaSO4 (15 %) failed. A Kaplan–Meier survival analysis showed that local antibiotic delivery with CaSO4 as the carrier material led to a significantly longer infection-free survival, considering any surgical revision (p<0.0001; hazard ratio 8.9 (95 % CI 2.8–28.2)) or revision with component exchange (p=0.0015; hazard ratio 5.6 (95 % CI 1.7–18.2)) as the endpoint. Conclusion: The addition of local antibiotics with CaSO4 as the carrier material to DAIR for PJIs after THA significantly increases success rates, such as infection-free survival, any reoperation, and revision with component exchange in particular.
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Suwanprateeb, J., F. Thammarakcharoen, P. Phanphiriya, W. Chokevivat, W. Suvannapruk, and B. Chernchujit. "PREPARATION AND CHARACTERIZATIONS OF ANTIBIOTIC IMPREGNATED MICROPOROUS NANO-HYDROXYAPATITE FOR OSTEOMYELITIS TREATMENT." Biomedical Engineering: Applications, Basis and Communications 26, no. 03 (March 17, 2014): 1450041. http://dx.doi.org/10.4015/s1016237214500410.
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In this study, preparation and characterization of antibiotic-impregnated microporous nano-hydroxyapatite (HA) aiming to function as both antibiotic carrier and bone graft for osteomyelitis treatment were carried out. Microporous nano-hydroxyapatite was prepared by low temperature phosphorization of three-dimensional printed calcium sulfate sample and was impregnated by three types of antibiotics including vancomycin, fosfomycin and gentamicin. Materials properties and antibacterial performance including phase composition, microstructure, degradability, total drug loading, antibacterial activity and shelf life were investigated and reported. Microporous nano-hydroxyapatite having porosity and mean pore size of 63.92% and 0.15 microns was prepared and showed greater resorbability than typical high-temperature sintering samples. Sustained release of antibiotic from the impregnated samples for longer than 29 days was observed, but the difference in the efficiency was related to the difference in the molecular weight, mechanism of action, spectrum of activity of each antibiotic. No deterioration in the antibacterial activity of the prepared antibiotic-impregnated hydroxyapatite was observed after storing for up to 12 months. No cytotoxic potential by MTT assay at all extraction periods was observed for vancomycin-impregnated hydroxyapatite. Gentamicin and fosfomycin impregnated hydroxyapatites showed cytotoxic potential only on day 1 extraction, but no cytotoxic potential was observed on day 2 extraction onward. This could be related to the concentration and characteristics of each released antibiotics.
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Bormann, Nicole, Aysha Schmock, Anja Hanke, Volker Eras, Norus Ahmed, Maya S. Kissner, Britt Wildemann, and Jan C. Brune. "Analysis of the Ability of Different Allografts to Act as Carrier Grafts for Local Drug Delivery." Journal of Functional Biomaterials 14, no. 6 (June 1, 2023): 305. http://dx.doi.org/10.3390/jfb14060305.
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Bone defects and infections pose significant challenges for treatment, requiring a comprehensive approach for prevention and treatment. Thus, this study sought to evaluate the efficacy of various bone allografts in the absorption and release of antibiotics. A specially designed high-absorbency, high-surface-area carrier graft composed of human demineralized cortical fibers and granulated cancellous bone (fibrous graft) was compared to different human bone allograft types. The groups tested here were three fibrous grafts with rehydration rates of 2.7, 4, and 8 mL/g (F(2.7), F(4), and F(8)); demineralized bone matrix (DBM); cortical granules; mineralized cancellous bone; and demineralized cancellous bone. The absorption capacity of the bone grafts was assessed after rehydration, the duration of absorption varied from 5 to 30 min, and the elution kinetics of gentamicin were determined over 21 days. Furthermore, antimicrobial activity was assessed using a zone of inhibition (ZOI) test with S. aureus. The fibrous grafts exhibited the greatest tissue matrix absorption capacity, while the mineralized cancellous bone revealed the lowest matrix-bound absorption capacity. For F(2.7) and F(4), a greater elution of gentamicin was observed from 4 h and continuously over the first 3 days when compared to the other grafts. Release kinetics were only marginally affected by the varied incubation times. The enhanced absorption capacity of the fibrous grafts resulted in a prolonged antibiotic release and activity. Therefore, fibrous grafts can serve as suitable carrier grafts, as they are able to retain fluids such as antibiotics at their intended destinations, are easy to handle, and allow for a prolonged antibiotic release. Application of these fibrous grafts can enable surgeons to provide longer courses of antibiotic administration for septic orthopedic indications, thus minimizing infections.
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Wahl, Peter, Karolin Rönn, Marc Bohner, Laurent A. Decosterd, Christoph Meier, Michel Schläppi, Sandrine Festa, and Emanuel Gautier. "In vitro study of new combinations for local antibiotic therapy with calcium sulphate - Near constant release of ceftriaxone offers new treatment options." Journal of Bone and Joint Infection 3, no. 4 (October 4, 2018): 212–21. http://dx.doi.org/10.7150/jbji.26218.
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Abstract. Introduction: Local application of antibiotics provides high concentrations at the site of interest, with minimal systemic toxicity. Carrier materials might help manage dead space. Calcium sulphate (CaSO4) has a dissolution time that only slightly exceeds the usually recommended duration of systemic antibiotic treatments. This in vitro study evaluates compatibility, release kinetics and antibacterial activity of new combinations of antibiotics with CaSO4 as carrier material.Methods: CaSO4 pellets added with 8% w/w antibiotic powder were exposed once in phosphate-buffered saline (PBS) solution and once in bovine plasma, in an elution experiment run over 6 weeks at 37 °C. Antibiotic elution was examined at various time points. Concentration was measured by liquid chromatography with tandem mass spectrometry. Antimicrobial activity was checked with an agar diffusion test.Results: Piperacillin-tazobactam, ceftazidime, cefepime, and meropenem showed fast reduction of concentration and activity. Flucloxacillin and cefuroxime remained present in relevant concentrations for 4 weeks. Ciprofloxacin, levofloxacin and clindamycin lasted for 6 weeks, but also at cell toxic concentrations. Ceftriaxone showed a near-constant release with only a small reduction of concentration from 130 to 75 mg/l. Elution profiles from PBS and plasma were comparable.Conclusion: CaSO4 provides new possibilities in the local treatment of bone and joint infections. Ceftriaxone appears to be of particular interest in combination with CaSO4. Release persists at clinically promising concentrations, and appears to have a depot-like slow release from CaSO4, with only a small reduction in activity and concentration over 6 weeks. To the best of our knowledge, such a particular persistent release never was described before, for any antibiotic in combination with a carrier material for local application.
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Wu, Lei, Xinqiang Xie, Ying Li, Tingting Liang, Haojie Zhong, Jun Ma, Lingshuang Yang, et al. "Metagenomics-Based Analysis of the Age-Related Cumulative Effect of Antibiotic Resistance Genes in Gut Microbiota." Antibiotics 10, no. 8 (August 20, 2021): 1006. http://dx.doi.org/10.3390/antibiotics10081006.
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Antibiotic resistance in bacteria has become a major global health problem. One of the main reservoirs of antibiotic resistance genes is the human gut microbiota. To characterise these genes, a metagenomic approach was used. In this study, a comprehensive antibiotic resistome catalog was established using fecal samples from 246 healthy individuals from world’s longevity township in Jiaoling, China. In total, 606 antibiotic resistance genes were detected. Our results indicated that antibiotic resistance genes in the human gut microbiota accumulate and become more complex with age as older groups harbour the highest abundance of these genes. Tetracycline resistance gene type tetQ was the most abundant group of antibiotic resistance genes in gut microbiota, and the main carrier of antibiotic resistance genes was Bacteroides. Antibiotic efflux, inactivation, and target alteration were found to be the dominant antimicrobial resistance mechanisms. This research may help to establish a comprehensive antibiotic resistance catalog that includes extremely long-lived healthy people such as centenarians, and may provide potential recommendations for controlling the use of antibiotics.
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Bischoff, Werner E., Michelle L. Wallis, Keith B. Tucker, Beth A. Reboussin, and Robert J. Sherertz. "Staphylococcus aureusNasal Carriage in a Student Community Prevalence, Clonal Relationships, and Risk Factors." Infection Control & Hospital Epidemiology 25, no. 6 (June 2004): 485–91. http://dx.doi.org/10.1086/502427.
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AbstractObjective:To evaluate the prevalence and risk factors of nasalStaphylococcus aureus(SA) in the community.Design:Cross-sectional study.Setting:Wake Forest University, Winston-Salem, North Carolina.Participants:Four hundred fifty students were screened for nasal SA carriage during the fall of 2000, 2001, and 2002.Methods:Students were screened by nose swabs. A self-administered questionnaire collected information on demographics and medical history. Antibiotic testing and PFGE were performed on isolates. Risk factors were determined by logistic regression analysis.Results:Of 450 volunteers, 131 (29%) were SA carriers. Antibiotic resistance was high for azithromycin (26%) and low for ciprofloxacin (1%), tetracycline (5%), mupirocin (1%), and methicillin (2%). PFGE patterns were not associated with carriage. Age, male gender, white race, medical student, allergen injection therapy, chronic sinusitis, rheumatoid arthritis, hospitalization for 6 months or less, and use of antibiotics were associated with carrier status by univariate analysis. Stepwise multivariate logistic regression led to a best fitting model with older age (OR, 1.04; CI95, 1.005-1.079), male gender (OR, 1.50; CI95, 0.982-2.296), and chronic sinusitis (OR, 2.71; CI95, 0.897-8.195) as risk factors. Antibiotic use (< 4 weeks) (OR, 0.41; CI95, 0.152-1.095) and allergen injection therapy (OR 0.41; CI95, 0.133-1.238) were protective. Analyses of carriers revealed candidate factors for persistent carriage to be nasal SA colonization rate and male gender. Factors for azithromycin resistance were non-medical students and antibiotic use in the past 6 months.Conclusion:Older male volunteers suffering from chronic sinusitis and not taking antibiotics were at higher risk for carrying SA.
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Yao, Jiangwei, Robert A. Carter, Grégoire Vuagniaux, Maryse Barbier, Jason W. Rosch, and Charles O. Rock. "A Pathogen-Selective Antibiotic Minimizes Disturbance to the Microbiome." Antimicrobial Agents and Chemotherapy 60, no. 7 (May 9, 2016): 4264–73. http://dx.doi.org/10.1128/aac.00535-16.
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ABSTRACTBroad-spectrum antibiotic therapy decimates the gut microbiome, resulting in a variety of negative health consequences. Debio 1452 is a staphylococcus-selective enoyl-acyl carrier protein reductase (FabI) inhibitor under clinical development and was used to determine whether treatment with pathogen-selective antibiotics would minimize disturbance to the microbiome. The effect of oral Debio 1452 on the microbiota of mice was compared to the effects of four commonly used broad-spectrum oral antibiotics. During the 10 days of oral Debio 1452 treatment, there was minimal disturbance to the gut bacterial abundance and composition, with only the unclassified S24-7 taxon reduced at days 6 and 10. In comparison, broad-spectrum oral antibiotics caused ∼100- to 4,000-fold decreases in gut bacterial abundance and severely altered the microbial composition. The gut bacterial abundance and composition of Debio 1452-treated mice were indistinguishable from those of untreated mice 2 days after the antibiotic treatment was stopped. In contrast, the bacterial abundance in broad-spectrum-antibiotic-treated mice took up to 7 days to recover, and the gut composition of the broad-spectrum-antibiotic-treated mice remained different from that of the control group 20 days after the cessation of antibiotic treatment. These results illustrate that a pathogen-selective approach to antibiotic development will minimize disturbance to the gut microbiome.
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Cho, B. O., H. H. Gim, Y. C. Lee, S. I. Jeong, S. Y. Jung, I. C. Kwon, and K. W. Choi. "The effect of fibrin glue as a local antibiotic carrier." International Journal of Oral and Maxillofacial Surgery 26 (January 1997): 251–52. http://dx.doi.org/10.1016/s0901-5027(97)81585-8.
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Cieslak, Erin, James P. Mack, and Albert Rojtman. "ESSENTIAL OILS AND METHYLGLYOXAL: A POSSIBLE ALTERNATIVE TREATMENT FOR ANTIBIOTIC RESISTANT BACTERIAL INFECTIONS." International Journal of Pharmacy and Pharmaceutical Sciences 8, no. 9 (September 1, 2016): 107. http://dx.doi.org/10.22159/ijpps.2016.v8i9.12242.
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<p><strong>Objective: </strong>Essential oils are of significant interest in today’s world of healthcare because these compounds have a variety of medicinal properties. In this study, we evaluated the <em>in vitro</em> antibiotic role of essential oils as a possible alternative treatment in combatting Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA).</p><p><strong>Methods: </strong>In conjunction with carrier oils, three essential oils (cassia, cinnamon bark, and thyme), as well as methylglyoxal were tested on MRSA using the Kirby-Bauer disc diffusion method.</p><p><strong>Results: </strong>The minimum inhibitory concentration of each tested essential oil and methylglyoxal in carrier oil was determined to be 25% essential oil and 75% carrier oil mixture. This concentration worked much more effectively than the standard antibiotic, vancomycin, which is currently used to treat MRSA infections.</p><p><strong>Conclusion: </strong>Antibacterial emollients made from naturally occurring products like essential oils can be cost-effective alternatives to antibiotics. The results of this research show that these emollients are more effective against MRSA than standard antibiotics in cell culture.</p>
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Sebastian, Sujeesh, Felix Tandberg, Yang Liu, Deepak B. Raina, Magnus Tägil, Mattias Collin, and Lars Lidgren. "Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin." Bone & Joint Research 11, no. 11 (November 1, 2022): 787–802. http://dx.doi.org/10.1302/2046-3758.1111.bjr-2022-0101.r1.
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Aims There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). Methods The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. Results Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. Conclusion Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802.
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Alduina, Rosa, Delia Gambino, Alessandro Presentato, Antonino Gentile, Arianna Sucato, Dario Savoca, Serena Filippello, et al. "Is Caretta Caretta a Carrier of Antibiotic Resistance in the Mediterranean Sea?" Antibiotics 9, no. 3 (March 10, 2020): 116. http://dx.doi.org/10.3390/antibiotics9030116.
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Sea turtles can be considered a sentinel species for monitoring the health of marine ecosystems, acting, at the same time, as a carrier of microorganisms. Indeed, sea turtles can acquire the microbiota from their reproductive sites and feeding, contributing to the diffusion of antibiotic-resistant strains to uncontaminated environments. This study aims to unveil the presence of antibiotic-resistant bacteria in (i) loggerhead sea turtles stranded along the coast of Sicily (Mediterranean Sea), (ii) unhatched and/or hatched eggs, (iii) sand from the turtles’ nest and (iv) seawater. Forty-four bacterial strains were isolated and identified by conventional biochemical tests and 16S rDNA sequencing. The Gram-negative Aeromonas and Vibrio species were mainly found in sea turtles and seawater samples, respectively. Conversely, the Gram-positive Bacillus, Streptococcus, and Staphylococcus strains were mostly isolated from eggs and sand. The antimicrobial resistance profile of the isolates revealed that these strains were resistant to cefazolin (95.5%), streptomycin (43.2%), colistin and amoxicillin/clavulanic acid (34.1%). Moreover, metagenome analysis unveiled the presence of both antibiotic and heavy metal resistance genes, as well as the mobile element class 1 integron at an alarming percentage rate. Our results suggest that Caretta caretta could be considered a carrier of antibiotic-resistant genes.
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Phanphiriya, P., Faungchat Thammarakcharoen, Watchara Chokevivat, and Jintamai Suwanprateeb. "Antimicrobial Performance and Cytotoxicity of Antibiotics Impregnated Hydroxyapatite for Osteomyelitis Treatment." Advanced Materials Research 506 (April 2012): 513–16. http://dx.doi.org/10.4028/www.scientific.net/amr.506.513.
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Localized antibiotic beads are often used for treating patients with osteomyelitis or infections of the bone by providing local, sustained and high concentrations of antimicrobial agents to the area of infection, without systemically exposing an individual to antibiotic levels that could result in numerous toxic side effects. In this study, antibiotic impregnated hydroxyapatite spheres were prepared aiming for a functional device of drug carrier and bone graft. Three types of antibiotics were employed including gentamicin, vancomycin and fosfomycin. Antimicrobial susceptibility of antibiotic impregnated beads were tested against two bacterial strains (Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 25923) by using modified agar diffusion assay. Differences in antimicrobial efficiency were observed and related with respect to differences in molecular weight, mechanism of action and spectrum of activity for each antibiotic. Cytotoxicity by serial extraction technique of all antibiotic impregnated beads were determined by MTT assay. No cytotoxic potential at all extraction periods was observed for vancomycin impregnated on beads. Gentamicin and fosfomycin impregnated beads showed cytotoxic potential only on day 1 extraction, but no cytotoxic potential on longer periods.
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Troiano, E., P. Giacomo, M. Di Meglio, N. Nuvoli, N. Mondanelli, S. Giannotti, and N. C. Orlandi. "STIMULAN® IN ORTHOPAEDIC SURGERY: TECHNIQUE AND INDICATIONS FOR USE." Orthopaedic Proceedings 105-B, SUPP_7 (April 4, 2023): 95. http://dx.doi.org/10.1302/1358-992x.2023.7.095.
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Infections represent a devastating complication in orthopedic and traumatological surgery, with high rates of morbidity and mortality. An early intervention is essential, and it includes a radical surgical approach supported by targeted intravenous antimicrobial therapy. The availability of parenteral antibiotics at the site of infection is usually poor, so it is crucial to maximize local antibiotic concentration using local carriers. Our work aims to describe the uses of one of these systems, Stimulan®, for the management and prevention of infections at our Institution.Analysing the reported uses of Stimulan®, we identified two major groups: bone substitute and carrier material for local antibiotic therapy. The first group includes its application as a filler of dead spaces within bone or soft tissues resulting from traumatic events or previous surgery. The second group comprehends the use of Stimulan® for the treatment of osteomyelitis, post-traumatic septic events, periprosthetic joint infections, arthroplasty revision surgery, prevention in open fractures, surgery of the diabetic foot, oncological surgery and for all those patients susceptible to a high risk of infection.We used Stimulan® in several complex clinical situations: in PJIs, in DAPRI procedure and both during the first and the second stage of a 2-stage revision surgery; furthermore, we started to exploit this antibiotic carrier also in prophylaxis of surgical site infections, as it happens in open fractures, and when a surgical site remediation is required, like in osteomyelitis following ORIF. Stimulan® is an extremely versatile and polyhedric material, available in the form of beads or paste, and can be mixed to a very broad range of antibiotics to better adapt to different bacteria and their antibiograms, and to surgeon's needs. These properties make it a very useful adjuvant for the management of complex cases of infection, and for their prevention, as well.
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Brieke, Clara, Veronika Kratzig, Kristina Haslinger, Andreas Winkler, and Max J. Cryle. "Rapid access to glycopeptide antibiotic precursor peptides coupled with cytochrome P450-mediated catalysis: towards a biomimetic synthesis of glycopeptide antibiotics." Organic & Biomolecular Chemistry 13, no. 7 (2015): 2012–21. http://dx.doi.org/10.1039/c4ob02452d.
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Fukuoka, Satoshi, Hideki Obika, Hiroshi Kamishima, Yoshinari Kobayashi, and Keishi Tenma. "Fabrication of sodium alginate fiber and its application to antibiotic carrier." Sen'i Gakkaishi 48, no. 1 (1992): 42–46. http://dx.doi.org/10.2115/fiber.48.42.
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Wijaya, Christian J., Stephanie N. Saputra, Felycia E. Soetaredjo, Jindrayani N. Putro, Chun X. Lin, Alfin Kurniawan, Yi-Hsu Ju, and Suryadi Ismadji. "Cellulose nanocrystals from passion fruit peels waste as antibiotic drug carrier." Carbohydrate Polymers 175 (November 2017): 370–76. http://dx.doi.org/10.1016/j.carbpol.2017.08.004.
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Labbaf, Sheyda, Harry Horsley, Ming-Wei Chang, Eleanor Stride, James Malone-Lee, Mohan Edirisinghe, and Jennifer L. Rohn. "An encapsulated drug delivery system for recalcitrant urinary tract infection." Journal of The Royal Society Interface 10, no. 89 (December 6, 2013): 20130747. http://dx.doi.org/10.1098/rsif.2013.0747.
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One of the hallmarks of urinary tract infection, a serious global disease, is its tendency to recur. Uropathogenic bacteria can invade cells lining the bladder, where they form longer-term intracellular reservoirs shielded from antibiotics, re-emerging at a later date to initiate flare-ups. In these cases, only lengthy systemic antibiotic treatment can eradicate all the reservoirs. Yet, long courses of antibiotics are not ideal, as they can lead to side effects and an increase in antibiotic resistance. Moreover, most antibiotics lose some potency by the time they reach the bladder, and many cannot permeate cells, so they cannot access intracellular reservoirs. Here, using coaxial electrohydrodynamic forming, we developed novel core–shell capsules containing antibiotics as a prototype for a future product that could be infused directly into the bladder. Gentamicin was encapsulated in a polymeric carrier (polymethylsilsesquioxane) and these capsules killed Enterococcus faecalis , a common chronic uropathogen, in vitro in a dose-responsive, slow-release manner. Capsules containing a fluorescent tracer dye in place of gentamicin penetrated human bladder cells and released their dye cargo with no apparent toxicity, confirming their ability to successfully permeate cells. These results suggest that such antibiotic capsules could prove useful in the treatment of recalcitrant UTI.
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Six, David A., Yanqiu Yuan, Jennifer A. Leeds, and Timothy C. Meredith. "Deletion of the β-Acetoacetyl Synthase FabY in Pseudomonas aeruginosa Induces Hypoacylation of Lipopolysaccharide and Increases Antimicrobial Susceptibility." Antimicrobial Agents and Chemotherapy 58, no. 1 (October 21, 2013): 153–61. http://dx.doi.org/10.1128/aac.01804-13.
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ABSTRACTThe β-acetoacetyl-acyl carrier protein synthase FabY is a key enzyme in the initiation of fatty acid biosynthesis inPseudomonas aeruginosa. Deletion offabYresults in an increased susceptibility ofP. aeruginosain vitroto a number of antibiotics, including vancomycin and cephalosporins. Because antibiotic susceptibility can be influenced by changes in membrane lipid composition, we determined the total fatty acid profile of the ΔfabYmutant, which suggested alterations in the lipid A region of the lipopolysaccharide. The majority of lipid A species in the ΔfabYmutant lacked a single secondary lauroyl group, resulting in hypoacylated lipid A. Adding exogenous fatty acids to the growth media restored the wild-type antibiotic susceptibility profile and the wild-type lipid A fatty acid profile. We suggest that incorporation of hypoacylated lipid A species into the outer membrane contributes to the shift in the antibiotic susceptibility profile of the ΔfabYmutant.
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Skopicki, H. A., D. Zikos, E. J. Sukowski, K. A. Fisher, and D. R. Peterson. "Gentamicin inhibits carrier-mediated dipeptide transport in kidney." American Journal of Physiology-Renal Physiology 270, no. 3 (March 1, 1996): F531—F538. http://dx.doi.org/10.1152/ajprenal.1996.270.3.f531.
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The effect of gentamicin on transport of pyroglutamylhistidine (pGlu-His) was examined in rabbit renal brush-border membrane vesicles (BBMV). Gentamicin, an aminoglycoside antibiotic, is limited in its usage because of nephrotoxicity characterized in part by transport defects in the proximal tubule. Since there is no information regarding the effects of gentamicin on renal peptide carriers, uptake of [3H]pGlu-His was measured in BBMV following either in vivo or in vitro exposure to the antibiotic. One hour after in vivo administration, the maximal rate (Vmax) for pGlu-His transport was significantly reduced in isolated membrane vesicles washed free of the drug, but the apparent Michaelis constant (Km) was unaltered. Coincubation of membranes with gentamicin during measurements of pGlu-His uptake had a similar effect, causing a significant decrease in the Vmax but not the Km of transport. The addition of 5 mM magnesium to the uptake medium prevented the in vitro but not the in vivo effect. The data indicate that high doses of gentamicin inhibit the capacity but not the affinity of dipeptide transport in the kidney, prior to morphological changes which typify acute tubular necrosis. The in vitro effect is rapid and involves a direct action of gentamicin on the brush-border membrane. The in vivo experiments show that toxicity may be prolonged and remains following removal of the drug from the renal brush border.
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Müller, Marik M., Ruslan Nedielkov, and Katja M. Arndt. "Strategies for Enzymatic Inactivation of the Veterinary Antibiotic Florfenicol." Antibiotics 11, no. 4 (March 25, 2022): 443. http://dx.doi.org/10.3390/antibiotics11040443.
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Large quantities of the antibiotic florfenicol are used in animal farming and aquaculture, contaminating the ecosystem with antibiotic residues and promoting antimicrobial resistance, ultimately leading to untreatable multidrug-resistant pathogens. Florfenicol-resistant bacteria often activate export mechanisms that result in resistance to various structurally unrelated antibiotics. We devised novel strategies for the enzymatic inactivation of florfenicol in different media, such as saltwater or milk. Using a combinatorial approach and selection, we optimized a hydrolase (EstDL136) for florfenicol cleavage. Reaction kinetics were followed by time-resolved NMR spectroscopy. Importantly, the hydrolase remained active in different media, such as saltwater or cow milk. Various environmentally-friendly application strategies for florfenicol inactivation were developed using the optimized hydrolase. As a potential filter device for cost-effective treatment of waste milk or aquacultural wastewater, the hydrolase was immobilized on Ni-NTA agarose or silica as carrier materials. In two further application examples, the hydrolase was used as cell extract or encapsulated with a semi-permeable membrane. This facilitated, for example, florfenicol inactivation in whole milk, which can help to treat waste milk from medicated cows, to be fed to calves without the risk of inducing antibiotic resistance. Enzymatic inactivation of antibiotics, in general, enables therapeutic intervention without promoting antibiotic resistance.
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Sebastian, S., M. Collin, Y. Liu, D. Raina, M. Tägil, and L. Lidgren. "ENHANCED STAPHYLOCOCCUS AUREUS ANTIBIOFILM ACTIVITY WITHOUT RESISTANCE DEVELOPMENT BY ADDING RIFAMPICIN TO A BIPHASIC CERAMIC CARRIER CONTAINING GENTAMICIN OR VANCOMYCIN." Orthopaedic Proceedings 105-B, SUPP_8 (April 11, 2023): 66. http://dx.doi.org/10.1302/1358-992x.2023.8.066.
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There is a lack of carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotic for Staphylococcus aureus deep bone infections (DBIs). RIF is also associated with systemic side effects, and known for causing rapid development of antibiotic resistance when given as monotherapy. We evaluated a clinically usedbi-phasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). It was hypothesized that this combined approach could provide improved biofilm eradication and prevent the development of RIF resistance.Methods: 1) Biofilm eradication: Using a modified crystal violet staining biofilm quantification method, the antibiotics released at different time points (Day 1, 3, 7, 14, 21, 28 and 35) from the hemispherical pellets of CaS/HA(500 mg)-VAN (24.57 mg) / GEN (10.35 mg) composites with or without RIF (8.11 mg) were tested for their ability to disrupt the preformed 48-h old biofilms of S. aureus ATCC 25923, and S. aureus clinical strain P-3 in 96-well microtitre plate. For each tested group of antibiotic fractions, five separate wells were used (n=5). 2) Testing for resistance development: Similar to the method mentioned above the 48-h biofilm embeded bacteria exposed to antibiotic fractions from different time points continuously for 7 days. The biofilms remained were then tested for RIF resistant strains of bacteria.Overall, there was clear antibiofilm biofilm activity observed with CaS/HA-VAN/GEN+RIF combinations compared with CaS/HA-VAN/GEN alone. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with combinations of CaS/HA-VAN/GEN+RIFEnhanced antibiofilm effects without development of RIF resistance indicates that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for additional local delivery in clinically demanding DBIs.Acknowledgement: We deeply acknowledge the Royal Fysiographic Society of Lund, Landshövding Per Westlings Minnesfond and the Stina and Gunnar Wiberg fond for financial support.
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Das, Manik, Partha Sakha Ghosh, and Kuntal Manna. "A Review on Platensimycin: A Selective FabF Inhibitor." International Journal of Medicinal Chemistry 2016 (January 28, 2016): 1–16. http://dx.doi.org/10.1155/2016/9706753.
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Emerging resistance to existing antibiotics is an inevitable matter of concern in the treatment of bacterial infection. Naturally occurring unique class of natural antibiotic, platensimycin, a secondary metabolite from Streptomyces platensis, is an excellent breakthrough in recent antibiotic research with unique structural pattern and significant antibacterial activity. β-Ketoacyl-(acyl-carrier-protein (ACP)) synthase (FabF) whose Gram-positive bacteria need to biosynthesize cell membranes is the target of inhibition of platensimycin. So, isolation, retrosynthetic analysis, synthesis of platensimycin, and analogues of platensimycin synthesized till today are the objectives of this review which may be helpful to further investigate and to reveal untouched area on this molecule and to obtain a potential antibacterial lead with enhanced significant antibacterial activity.
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Lawley, Trevor D., Simon Clare, Alan W. Walker, David Goulding, Richard A. Stabler, Nicholas Croucher, Piero Mastroeni, et al. "Antibiotic Treatment of Clostridium difficile Carrier Mice Triggers a Supershedder State, Spore-Mediated Transmission, and Severe Disease in Immunocompromised Hosts." Infection and Immunity 77, no. 9 (June 29, 2009): 3661–69. http://dx.doi.org/10.1128/iai.00558-09.
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ABSTRACT Clostridium difficile persists in hospitals by exploiting an infection cycle that is dependent on humans shedding highly resistant and infectious spores. Here we show that human virulent C. difficile can asymptomatically colonize the intestines of immunocompetent mice, establishing a carrier state that persists for many months. C. difficile carrier mice consistently shed low levels of spores but, surprisingly, do not transmit infection to cohabiting mice. However, antibiotic treatment of carriers triggers a highly contagious supershedder state, characterized by a dramatic reduction in the intestinal microbiota species diversity, C. difficile overgrowth, and excretion of high levels of spores. Stopping antibiotic treatment normally leads to recovery of the intestinal microbiota species diversity and suppresses C. difficile levels, although some mice persist in the supershedding state for extended periods. Spore-mediated transmission to immunocompetent mice treated with antibiotics results in self-limiting mucosal inflammation of the large intestine. In contrast, transmission to mice whose innate immune responses are compromised (Myd88−/−) leads to a severe intestinal disease that is often fatal. Thus, mice can be used to investigate distinct stages of the C. difficile infection cycle and can serve as a valuable surrogate for studying the spore-mediated transmission and interactions between C. difficile and the host and its microbiota, and the results obtained should guide infection control measures.
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Lukina, Yuliya, Yuriy Panov, Ludmila Panova, Aleksandr Senyagin, Leonid Bionyshev-Abramov, Natalya Serejnikova, Aleksey Kireynov, et al. "Chemically Bound Resorbable Ceramics as an Antibiotic Delivery System in the Treatment of Purulent–Septic Inflammation of Bone Tissue." Ceramics 5, no. 3 (July 27, 2022): 330–50. http://dx.doi.org/10.3390/ceramics5030026.
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Local drug delivery systems are an effective approach in the treatment of purulent–septic inflammation of bone tissue. Chemically bonded multiphase ceramics based on calcium-deficient carbonate-substituted hydroxyapatite combine resorbability, osteoconductivity, and the possibility of volumetric incorporation of antibiotics. Macroporosity is regulated by the concentration of polyethylene glycol granules introduced into the initial powder composition, followed by their extraction. The selected conditions for the consolidation of the ceramic matrix and the extraction of PEG granules retain the activity of vancomycin, which is confirmed by the results of microbiological studies. The concentration of vancomycin and the porosity affect the local concentration and release of the antibiotic. The incorporation method provides a prolonged release of the antibiotic for up to 31 days. In vivo experiments with bone implantation have shown that chemically bound macroporous ceramics with incorporated vancomycin are a therapeutically effective carrier of the substance during the healing of bone defects in conditions of surrounding purulent–septic inflammation, and can be considered as a carrier for local antibacterial therapy, at the site of implantation.
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Trusek, Anna, and Edward Kijak. "Drug Carriers Based on Graphene Oxide and Hydrogel: Opportunities and Challenges in Infection Control Tested by Amoxicillin Release." Materials 14, no. 12 (June 9, 2021): 3182. http://dx.doi.org/10.3390/ma14123182.
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Graphene oxide (GO) was proposed as an efficient carrier of antibiotics. The model drug, amoxicillin (AMOX), was attached to GO using a peptide linker (Leu-Leu-Gly). GO-AMOX was dispersed in a hydrogel to which the enzyme responsible for releasing AMOX from GO was also added. The drug molecules were released by enzymatic hydrolysis of the peptide bond in the linker. As the selected enzyme, bromelain, a plant enzyme, was used. The antibacterial nature of the carrier was determined by its ability to inhibit the growth of the Enterococcus faecalis strain, which is one of the bacterial species responsible for periodontal and root canal diseases. The prepared carrier contained only biocompatible substances, and the confirmation of its lack of cytotoxicity was verified based on the mouse fibrosarcoma cell line WEHI 164. The proposed type of preparation, as a universal carrier of many different antibiotic molecules, can be considered as a suitable solution in the treatment of inflammation in dentistry.
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Schaefer, John J., Jonathan Kahn, Glen R. Needham, Yasuko Rikihisa, S. A. Ewing, and R. W. Stich. "Antibiotic Clearance ofEhrlichia canisfrom Dogs Infected by Intravenous Inoculation of Carrier Blood." Annals of the New York Academy of Sciences 1149, no. 1 (December 2008): 263–69. http://dx.doi.org/10.1196/annals.1428.087.
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Mulzer, Johann, and Markus Berger. "Total Synthesis of the Boron-Containing Ion Carrier Antibiotic Macrodiolide Tartrolon B." Journal of Organic Chemistry 69, no. 3 (February 2004): 891–98. http://dx.doi.org/10.1021/jo035391p.
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