Search

In comparison to the efforts required to bring a new drug or formulation to the clinic, bestowing a name on a medicine is relatively simple. However, if the name we choose causes confusion—by making its contents ambiguous or if it is too alike another drug—it can precipitate clinical errors. This prompted the World Health Organization to set up the International Nonproprietary Naming Committee in the 1970s to select unambiguous names for drugs. Unfortunately, multidrug products—which are becoming increasingly popular—do not fall under the remit of conventional International Non‐proprietary Nomenclature. We have identified 26 combination formulations that have been historically named with the co‐drug format in the United Kingdom. Most of them have also been prescribed in the United Kingdom in the past year, and although several of them are not prescribed very often, 11 were prescribed more than 2000 times. In this paper, we have explored the literature to identify prescribing errors with co‐drug products and found several idiosyncrasies that have caused drug errors in the past. We advocate for a standard nomenclature (state the international nonproprietary name [INN] of each component followed by dose information in the x + y format) for these products on the box and in prescribing resources. We hope that this will enhance clarity and safety during prescribing and administration, particularly for high‐volume drugs like paracetamol + codeine (co‐codamol), amoxicillin + clavulanic acid (co‐amoxiclav) and trimethoprim + sulfamethoxazole (co‐trimoxazole). [ABSTRACT FROM AUTHOR]

The article presents a case study of a 17-year-old male who developed perforated appendicitis during the re-nourishment phase of treatment for an eating disorder. Topics discussed include the patient's significant weight loss and dietary practices, the medical team's management of his bradycardia and nutritional rehabilitation, and the complications that arose during hospitalization, ultimately leading to emergency surgery.

A liquid chromatography electrospray ionization tandem mass spectrometry method with amoxicillin‐d4 as the stable isotope‐labeled internal standard for simultaneous quick detection of amoxicillin and clavulanic acid in human plasma was developed and validated. Chromatographic separations were performed on a Hedera ODS‐2 column (2.1 × 150 mm, 5 μm). The mobile phases for gradient elution were aqueous solution containing 0.2% acetic acid (AA) (mobile phase A) together with organic phase solution (acetonitrile and methanol mixed solution, mobile phase B). Mass spectrometry was performed using negative electrospray ionization in multiple reaction monitoring mode. The target fragment ion pairs of amoxicillin, clavulanic acid and amoxicillin‐d4 were m/z 364.1 → 223.1, 198.1 → 135.9 and 368.1 → 227.1, respectively. The linear ranges of this method were 40–5,000 ng/ml for amoxicillin and 30–2,500 ng/ml for clavulanic acid, with coefficient of determination > 0.9900. This method validation included selectivity, standard curve, lower limit of quantitation, accuracy, precision, recovery, matrix effect (hemolytic matrix and hyperlipidemic matrix), carryover, stability, dilution reliability and incurred sample reanalysis study. A successful application of this method was realized in a pharmacokinetic study after administration of amoxicillin–clavulanic acid potassium granules. [ABSTRACT FROM AUTHOR]

Introduction: Individuals with inborn errors of immunity (IEI) are at increased risk of respiratory infection and frequently receive prolonged broad-spectrum antibiotics, leading to antibiotic resistance. The aim of this study was to identify respiratory pathogens and antibiotic resistance patterns in IEI patients. Methods: We retrospectively studied 36 IEI patients with positive bacterial growth in sputum cultures between 2014 and 2023. Data covered hospitalizations, respiratory infections, yearly antibiotic prescriptions, past sputum cultures, and antibiotic sensitivities. Patients with primary ciliary dyskinesia (PCD) and bronchiectasis served as a control group. Results: A total of 314 sputum cultures were analyzed from patients with IEI, alongside 585 cultures from individuals with PCD and 113 cultures from patients with bronchiectasis. Patients with IEI had a median age of 23.5 years, with 61% male participants. The study compared the differences in bacterial isolates from sputum cultures and antibiotic resistance between patients with IEI and the control groups. The most common bacterial isolates across all groups were Haemophilus influenzae (159 isolates in IEI vs. 314 in PCD and 26 in bronchiectasis), Pseudomonas aeruginosa, and Streptococcus pneumoniae. In IEI patients, 992 symptomatic respiratory exacerbations and 43 pneumonia-related hospitalizations were recorded. Notably, H. influenzae in IEI patients showed high resistance rates to cefuroxime (82%), amoxicillin/clavulanic acid (66%), trimethoprim/sulfamethoxazole (59%), and ampicillin/sulbactam (49%). P. aeruginosa in IEI patients displayed significant resistance to ciprofloxacin (85%), ceftazidime (42%), and aminoglycosides (23–33%). Additionally, all S. pneumoniae isolates in IEI patients were tetracycline resistant, with high resistance rates to penicillin, clindamycin, and erythromycin. It is essential to highlight the substantial resistance of common pathogens to oral antibiotics. In contrast, the control groups exhibited lower resistance rates across all bacterial isolates. Conclusion: Antimicrobial resistance is a growing concern among vulnerable IEI patients. We suggest conducting similar investigations in other regions to address this issue. The findings should inform future infection management guidelines for IEIs. [ABSTRACT FROM AUTHOR]

Community-acquired pneumonia (CAP) is an acute infection of the lung parenchyma acquired outside the hospital or other healthcare settings, typically affecting previously healthy individuals. This intersociety consensus aims to provide evidence-based recommendations for the antibiotic treatment of mild to moderate CAP in previously healthy children in Italy. A systematic review was conducted to identify the most recent and relevant evidence. Embase, Scopus, PubMed, and Cochrane databases were systematically screened, with a date restriction from 2012 to April 2024, but without language limitations. The review included studies conducted in high-income countries on antibiotic therapy in children over 3 months of age diagnosed with mild-moderate CAP. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methods. The final recommendations were obtained through a Delphi consensus of an expert panel. Amoxicillin is the first-line treatment if the child is at least immunized against Haemophilus influenzae type b (low/very low quality of evidence, strong recommendations), while amoxicillin-clavulanate or second- or third-generation cephalosporins should be prescribed for those unimmunized or with incomplete immunization coverage for both H. influenzae type b and Streptococcus pneumoniae (low/very low quality of evidence, strong recommendations). Macrolides should be considered in addition to amoxicillin in children over 5 years old, if symptoms persist and the clinical condition remains good after 48 h of therapy (low/very low quality of evidence, strong recommendations). The dosage of amoxicillin is 90 mg/kg/day divided in three doses, although two doses could be considered to improve compliance (moderate quality of evidence, weak recommendations). A five-day duration of therapy is recommended, with clinical monitoring and re-assessment approximately 72 h after the start of antibiotic treatment to evaluate symptom resolution (moderate quality of evidence, strong recommendations). To improve the management of CAP in pediatric patients, we have developed this consensus based on a thorough review of the best available evidence and extensive discussions with an expert panel. However, further efforts are needed. Future research should focus on enhancing diagnostic accuracy, optimizing antibiotic utilization, comparing the efficacy of different antibiotic regimens, and determining the optimal dosage and duration of treatment in different setting. [ABSTRACT FROM AUTHOR]

Streptomyces clavuligerus is a species used worldwide to industrially produce clavulanic acid (CA), a molecule that enhances antibiotic effectiveness against β-lactamase-producing bacterial strains. Despite its low inherent CA production, hyper-producing strains have been developed. However, genomic analyses specific to S. clavuligerus and CA biosynthesis are limited. Genomic variations that may influence CA yield were explored using S. clavuligerus strain genomes from diverse sources. Despite the slight differences obtained by similarity index calculation, pan-genome estimation revealed that only half of the genes identified were present in all strains. As expected, core genes were associated with primary metabolism, while the remaining genes were linked to secondary metabolism. Differences at the sequence level were more likely to be found in regions close to the tips of the linear chromosome. Wild-type strains preserved larger chromosomal and plasmid regions compared to industrial and/or hyper-producing strains; such a grouping pattern was also found through refined phylogenetic analyses. These results provide essential insights for the development of hyper-producing S. clavuligerus strains, attending to the critical demand for this antibiotic enhancer and contributing to future strategies for CA production optimization. [ABSTRACT FROM AUTHOR]

Background: Warfarin and Direct Oral Anticoagulant (DOAC) users may have more frequent antibiotic prescriptions than non-users. The aim of this study was to estimate rates of common and resistant infections, and antibiotic prescribing amongst warfarin and DOAC users versus non-users. Methods: This matched retrospective cohort study used data from patients registered with General practices in England contributing to the Clinical Practice Research Datalink GOLD. We included 61,750 adults who initiated warfarin or a DOAC between 1st January 2011 and 31st December 2019, matched 1:1 to non-users. We estimated Incident Rate Ratios (IRR) and 95% Confidence Intervals for three common infections and all-cause antibiotic prescribing. We estimated hazard ratios (HRs) and 95% CIs for the risk of methicillin resistance Staphylococcus aureus (MRSA), other antibiotic-resistant organisms, or Clostridium difficile. We assessed the extent to which any of the effect of warfarin and DOAC use on antibiotic resistant infections or Clostridium difficile was mediated by antibiotic prescribing patterns. Results: 37,143 warfarin users and 24,607 DOAC users were matched 1:1 to non-users. Warfarin and DOAC users had greater relative consultation rates for respiratory, urinary, and skin infections. All-cause antibiotic prescribing was greater in warfarin and DOAC users (warfarin; adjusted IRR 1.47, 95% CI 1.45–1.50, DOAC; adjusted IRR 1.66, 95% CI 1.63–1.69). Largest effect sizes were observed for flucloxacillin (adjusted IRR 2.11, 95% CI 2.01–2.20), and erythromycin (adjusted IRR 2.32, 95% CI 2.00–2.70). Warfarin users had significantly higher risk of MRSA (adjusted HR 1.68, 95% CI 1.38–2.05) and hospital admission with antibiotic resistant infections (adjusted HR 1.91, 95% CI 1.11–3.30). DOAC users had significantly higher risk of MRSA (adjusted HR 1.57, 95% CI 1.20–2.06), hospital admission with antibiotic resistant infections (adjusted HR 2.13, 95% CI 1.61–2.82), and Clostridium difficile (adjusted HR 1.45, 95% CI 1.10–1.92). We found little evidence to suggest that the increased risks of studied outcomes were mediated by rates of antibiotic prescription. Conclusion: Warfarin and DOAC use was associated with greater rates of infection consultations, all-cause antibiotic prescribing, antibiotic resistant infections, and Clostridium difficile, but there was little evidence that antibiotic prescribing rates mediated risk of resistant infections or Clostridium difficile. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment of neonatal pneumonia with N-acetyl cysteine (NAC) in calves shortens the time to symptom resolution by 27 h. There is a lack of data on NAC usage for neonatal pneumonia in calves. However, previous research explored its usage in other animals with other indications in cattle. The effects of NAC on neonatal pneumonia in calves were investigated in 40 animals from different owners who accepted or refused the addition of NAC in the therapy protocol. NAC has mucolytic, antioxidant, and antimicrobial effects in living organisms. However, the therapeutic effects of NAC on clinical recovery among neonatal calves with respiratory diseases have not yet been studied. Our study represents the first investigation of the effects of NAC in neonatal calves with pneumonia. The objective of this work was to observe the effects of NAC in the treatment of neonatal pneumonia, including its ability to reduce the clinical score, shorten the duration of the treatment, and improve the overall health condition of neonatal calves. For this study, calves were divided into two groups: a treatment group that received NAC and amoxicillin with clavulanic acid, and a control group that received amoxicillin with clavulanic acid (antimicrobial only). The findings of this study indicate that NAC treatment significantly shortened the time to resolution (p < 0.001), compared to the results in the group without NAC treatment. Generally, NAC-supplemented therapy reduced the recovery time by more than 27 h (or slightly more than one day), compared to that in the antimicrobial-only group. Our study presents the first reported usage of NAC in therapy for respiratory disorders. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the feasibility of capturing antimicrobial usage data from prisons for inclusion in the Antimicrobial Use and Resistance in Australia (AURA) surveillance system and to analyse 2021 and 2022 South Australian (SA) usage data for notable trends. Methods: Monthly antimicrobial supply data for eight SA prisons were collected. Antimicrobial volume was converted into the World Health Organization metric, defined daily doses (DDD). Usage rates were calculated relative to prison occupied bed days (OBD). Results: Annual usage of systemic antimicrobials across eight SA prisons totalled 26,448 DDD and 23,526 DDD in 2021 and 2022 respectively. Antibacterials accounted for 80.6% of all antimicrobials dispensed during the study period. The average antibacterial usage rate in female prisons was higher on average than in male prisons. The state-wide systemic antibacterial usage rate in SA prisons declined by 11.3% from 23.8 DDDs/1000 OBD in 2021 to 21.1 DDDs/1000 OBD. Doxycycline, amoxicillin, flucloxacillin, amoxicillin-clavulanic acid, and cefalexin accounted for 72% of the total systemic antibacterial usage rate. Variation in the oral and topical antifungal agents used and the rate of use was observed between prisons. Conclusions: This SA pilot study demonstrates the feasibility of including prisons in routine national antimicrobial surveillance using similar methodology to hospital surveillance. The contributing facilities comprised 6.1% of all Australian prison beds, and extrapolation of the results suggests that the identified gap in surveillance may equate to over 400,000 DDD per annum in prisons nationwide, equating to approximately 5% of hospital inpatient antimicrobial usage. What is known about the topic? Surveillance of antimicrobial use is a useful tool to identify overuse or inappropriate use and enable targeted interventions to optimise antimicrobial prescribing and reduce the risk of antimicrobial resistance. What does this paper add? The methodology currently used to monitor antimicrobial use in Australian hospitals could be utilised to conduct facility-level surveillance in Australian prisons and would provide a mechanism to benchmark use between facilities and identify unexpected or inappropriate use. What are the implications for practitioners? Surveillance of antimicrobial use in prisons would support prison healthcare workers to monitor use over time, identify any increasing or unexpected trends in use, and target educational interventions to ensure compliance with antimicrobial prescribing guidelines. [ABSTRACT FROM AUTHOR]

The association of amoxicillin and clavulanic acid has shown high efficacy to treat mastitis worldwide, also promoting a shorter milk disposal period compared to other antimicrobials. However, no previous investigations regarding its application to treat mastitis in Brazilian dairy cows were developed. This study evaluated the effectiveness of amoxicillin-clavulanic acid to treat Brazilian dairy cows with mastitis, comparing it with a reference protocol treatment combination of tetracycline, neomycin and bacitracin. Holstein cows (n = 468) from three different dairy herds in Brazil were assigned to two groups: combination of tetracycline, neomycin and bacitracin (n = 178; positive control group) and amoxicillin-clavulanic acid protocol (n = 290). Before the treatment, milk samples were collected and cultivated in chromogenic media. After finishing the antimicrobial treatment (intramammary), milk samples were also collected and cultivated in chromogenic media. Results from microbiological analysis obtained before and after treatment were compared to determine the healing rate. Nine different microbiological agents were identified: eight of environmental origin and one of contagious origin; being eight grampositive and one gram-negative bacteria. TThe positive control group and the treatment group showed similar healing rate (86.5% and 90.3%, respectively; P > 0.05). No differences were found between the groups for the healing rate, when the causing agent was considered. Therefore, it is possible to indicate the amoxicillin-clavulanic acid-based protocol to treat intramammary mastitis in Brazilian dairy cows, achieving great healing rates and providing a substantial reduction in milk disposal. [ABSTRACT FROM AUTHOR]

Clavulanic acid is a potent β-lactamase inhibitor produced by Streptomyces clavuligerus, widely used in combination with β-lactam antibiotics to combat antimicrobial resistance. This systematic review analyzes the most successful methodologies for clavulanic acid overproduction, focusing on the highest yields reported in bench-scale and bioreactor-scale fermentations. Studies have demonstrated that glycerol is the preferred carbon source for clavulanic acid production over other sources like starch and dextrins. The optimization of feeding strategies, especially in fed-batch operations, has improved glycerol utilization and extended the clavulanic acid production phase. Organic nitrogen sources, particularly soybean protein isolates and amino acid supplements such as L-arginine, L-threonine, and L-glutamate, have been proven effective at increasing CA yields both in batch and fed-batch cultures, especially when balanced with appropriate carbon sources. Strain engineering approaches, including mutagenesis and targeted genetic modifications, have allowed for the obtainment of overproducer S. clavuligerus strains. Specifically, engineering efforts that overexpress key regulatory genes such as ccaR and claR, or that disrupt competing pathways, redirect the metabolic flux towards CA biosynthesis, leading to high clavulanic acid titers. The fed-batch operation at the bioreactor scale emerges as the most feasible alternative for prolonged clavulanic acid production with both wild-type and mutant strains, allowing for the attainment of high titers during cultivations. [ABSTRACT FROM AUTHOR]

Recently, the German Federal Institute for Medicines and Medical Products restricted the use of fosfomycin in transrectal biopsy of the prostate (TRBP). Accordingly, the need for other antibiotic agents for prophylaxis in TRBP is urgent since antibiotic prophylaxis is mandatory in accordance with these guidelines. After the restriction of the use of ciprofloxacin, and before the use of fosfomycin in Germany was falsely allowed, amoxicillin/clavulanic acid was evaluated as an alternative for antibiotic prophylaxis in TRBP. Regarding hospitalization for post-interventional infections, 359 patients at the Department of Urology of the University of Regensburg, at Caritas-St. Josef Medical Center as a single center, underwent TRBP between 2 July 2019 and 30 June 2020. Regarding antibiotic prophylaxis, the post-interventional hospitalization rate due to bacterial complications was relevant. Of the 359 patients, 10 (2.8%) had an infection requiring hospitalization post-TRBP. A total of 349 (97.2%) patients had no infection-related hospitalization. This corresponds to an incidence rate of only 2.8%. Referring to the previous infection rates under the now obsolete ciprofloxacin, amoxicillin/clavulanic acid can show a similar, if not tendentially even lower, risk of infection, and so this substance can be an alternative for antibiotic prophylaxis in TRBP. Another advantage is that, according to the WHO's AWaRe classification, amoxicillin/clavulanic acid is one of the so-called Access antibiotics. This study is limited as rectal swabs and urine cultures were not performed on every patient before TRBP. [ABSTRACT FROM AUTHOR]

The swine production chain can be a reservoir of antimicrobial-resistant Escherichia coli, which transfers resistance genes to other bacteria, serving as an important biomarker in the One Health approach. This study aimed to identify the frequency and antimicrobial resistance profile of E. coli in the swine production chain, assess the presence of extended-spectrum beta-lactamases (ESBL), and compare resistance profiles across different sample types. A total of 622 samples of swine carcasses from various points of the slaughter process (n = 400), swine feces (n = 100), commercial cuts (n = 45), environment (n = 67), and feces from employees (n = 10) of a pig slaughterhouse certified by the Federal Inspection Service, located in São Paulo state, Brazil, were collected. A total of 1260 E. coli isolates were obtained from the samples, with 73.6% of the samples testing positive. The agar disk diffusion test was performed with 10 different classes of antimicrobials. To confirm the production of ESBLs, the isolates were submitted to a double-disk synergism test using cefotaxime, ceftazidime, and amoxicillin with clavulanic acid. Of the total isolates, 80.71% were multidrug resistant. All ESBL-producing isolates were multidrug resistant and resistant to amoxicillin, tetracycline, and chloramphenicol. Isolates from human feces samples had less chance of being multidrug resistant than samples from other sources. The diversity of resistance profiles was verified in the samples, not clustering according to the sources, except for human feces isolates that clustered, evidencing lower antimicrobial resistance variability of these samples. Antimicrobial resistance is significantly present in the pork production chain, necessitating a comprehensive multidisciplinary approach to effectively mitigate risks within the One Health framework. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion The current treatment for Buruli ulcer is based on empirical evidence of efficacy. However, there is an opportunity for shortening its duration and improving response rates. Evolving understanding of the pharmacokinetic–pharmacodynamic relationships provides the basis for a stronger dose rationale for antibiotics. In conjunction with modelling and simulation, it is possible to identify dosing regimens with the highest probability of target attainment (PTA). This investigation aims to: (i) assess the dose rationale for a new combination therapy including amoxicillin/clavulanic acid (AMX/CLV) currently in clinical trials; and (ii) compare its performance with alternative dosing regimens including rifampicin, clarithromycin and AMX/CLV.In vitro estimates of the minimum inhibitory (MIC) concentration were selected as a measure of the antibacterial activity of different drug combinations. Clinical trial simulations were used to characterize the concentration vs. time profiles of rifampicin, clarithromycin and amoxicillin in a virtual cohort of adult and paediatric patients, considering the effect of baseline covariates on disposition parameters and interindividual variability in exposure. The PTA of each regimen was then assessed using different thresholds of the time above MIC.A weight‐banded dosing regimen including 150–600 mg rifampicin once daily, 250–1000 mg clarithromycin and AMX/CLV 22.5 mg/kg /1000 mg twice daily ensures higher PTA than the standard of care with AMX/CLV 45 mg/kg/2000 mg once daily.The higher PTA values support the proposed 4‐drug combination (rifampicin, clarithromycin, AMX/CLV) currently under clinical investigation. Our findings also suggest that higher rifampicin doses might contribute to enhanced treatment efficacy. [ABSTRACT FROM AUTHOR]

Invasive sinusitis is a rare complication of sinusitis. We present the case of a woman, age 72 years, who presented with acute encephalopathy in the setting of sepsis found to have extensive invasive sinusitis with intracranial extension secondary to Streptococcus intermedius, managed with intravenous antibiotics alone. S. intermedius is a rare cause of acute bacterial sinusitis, associated with infections of relatively greater severity and risk of intracranial spread, often requiring a combination of intravenous antibiotics and surgical debridement for source control. Successful treatment of invasive sinusitis with medical management alone may be achievable if surgical intervention is contraindicated. However, the probability of meaningful recovery without surgical source control is rare and is associated with greater morbidity and mortality. Therefore, factors contributing to the success of medical management alone should be investigated. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to assess antibiotic prescribing and use patterns at the Department of Surgery, Korle Bu Teaching Hospital. Design: A cross-sectional study design was employed in this study. Setting: The study was conducted at the Department of Surgery, Korle Bu Teaching Hospital. Participants: Forty-two prescribers out of 63 (67%) at the Department of Surgery responded to questionnaires. Over the study period, prescriptions and medical records of 1715 patients from the general surgery, neurosurgery, and urology units were reviewed. Main Outcome Measures: Percentage of prescriptions with antibiotics, percentage of prescribers using guidelines for antibiotic prescriptions, and percentage using culture and sensitivity to inform antibiotic prescriptions. Results: Of the 1715 prescriptions assessed, 75% (1294/1715) were from inpatients, and 45% (772/1715) included an antibiotic. Ciprofloxacin and metronidazole constituted 54% of antibiotic prescriptions from general surgery. Amoxicillin/ clavulanic acid and ceftriaxone constituted 64.7% of antibiotic prescriptions from neurosurgery, and ceftriaxone and ciprofloxacin made up 37.7% of antibiotic prescriptions from urology. Microbiology testing was done for only 14.5% (9/62) of inpatients who received antibiotics for treatment. The choice of antibiotics was influenced mainly by doctors' previous experience (37/42, 88.1%). Conclusion: Antibiotics are widely used. About half of all prescriptions had antibiotics, with ciprofloxacin and metronidazole constituting more than half of antibiotic prescriptions from general surgery. Doctors mainly based their antibiotic prescriptions on previous experience and occasionally on microbiological investigations. [ABSTRACT FROM AUTHOR]

Objective: To describe the development of uroabdomen secondary to spontaneous bladder rupture in a dog with dystocia. Case Summary: A 2‐year‐old intact female Boston Terrier was referred for prolonged labor of 72 hours. At presentation, the dog had delivered 8 puppies at home, with the last pup being stillborn. The dog was in hypovolemic shock and had free abdominal effusion. Abdominal radiographs showed no evidence of remaining fetuses. Abdominal fluid analysis revealed a fluid potassium that was 1.8 times higher than the peripheral blood potassium. Retrograde positive contrast cystography identified leakage of contrast into the abdomen, consistent with uroabdomen secondary to bladder rupture. Bloodwork abnormalities included a mild monocytic leukocytosis with a left shift, moderate azotemia, mild hyperbilirubinemia, mild increase of alkaline phosphatase activity, moderate hyponatremia, and moderate hypochloremia. The dog was resuscitated with IV fluids and received IV antimicrobials out of concerns for septic peritonitis and sepsis. An exploratory laparotomy revealed a moderate volume abdominal effusion, uterine enlargement with no identifiable fetuses, and a small rupture of the urinary bladder wall apex. The bladder wall defect was repaired, and the dog underwent an ovariohysterectomy. Perioperative systemic hypotension was treated with a norepinephrine constant rate infusion and resolved within 24 hours. The dog was discharged 5 days later. The combined peritoneal fluid and uterine fluid culture and sensitivity testing revealed Enterococcus spp. and Staphylococcus pseudintermedius, both susceptible to amoxicillin/clavulanic acid and enrofloxacin. Bladder wall histopathology revealed severe mural congestion, edema, and hemorrhage, without evidence of neoplasia, cystitis, or urolithiasis. Unique Information Provided: This is the first case report of a dog with uroabdomen secondary to a bladder wall rupture associated with dystocia. Early recognition of this rare phenomenon and vigilance in treatment is essential for a good prognosis and outcome. [ABSTRACT FROM AUTHOR]

Some antibiotics that are frequently employed are β-lactams. In light of the hydrolytic process of β-lactamase, found in Gram-negative bacteria, inhibitors of β-lactamase (BLIs) have been produced. Examples of first-generation β-lactamase inhibitors include sulbactam, clavulanic acid, and tazobactam. Many kinds of bacteria immune to inhibitors have appeared, and none cover all the β-lactamase classes. Various methods have been utilized to develop second-generation β-lactamase inhibitors possessing new structures and facilitate the formation of diazabicyclooctane (DBO), cyclic boronate, metallo-, and dual-nature β-lactamase inhibitors. This review describes numerous promising second-generation β-lactamase inhibitors, including vaborbactam, avibactam, and cyclic boronate serine-β-lactamase inhibitors. Furthermore, it covers developments and methods for synthesizing MβL (metallo-β-lactamase inhibitors), which are clinically effective, as well as the various dual-nature-based inhibitors of β-lactamases that have been developed. Several combinations are still only used in preclinical or clinical research, although only a few are currently used in clinics. This review comprises materials on the research progress of BLIs over the last five years. It highlights the ongoing need to produce new and unique BLIs to counter the appearance of multidrug-resistant bacteria. At present, second-generation BLIs represent an efficient and successful strategy. [ABSTRACT FROM AUTHOR]

Background: The escalating resistance of uropathogens in pediatric febrile urinary tract infection (F-UTI) is a global concern. This study examined changing trends in F-UTI epidemiology and resistance patterns among Israeli pediatric inpatients over a decade. Methods: Demographic, clinical, and laboratory data for children between 3 months and 18 years old with febrile UTI from 2010 to 2021 were retrieved from electronic medical records. Results: A total of 761 cases of F-UTI were identified (702 females, mean age 43 months). Escherichia coli was the most common pathogen (85.9%), followed by Pseudomonas aeruginosa (3.5%) and Klebsiella pneumoniae (3.4%). Compared with the non-complicated UTI group, the complicated UTI group had significantly higher rates of Pseudomonas aeruginosa (5.3% vs. 1.0%, p = 0.002) and Klebsiella pneumoniae (4.6% vs. 1.6%, p = 0.03). Antibiotic resistance analysis revealed significant differences between the groups: resistance to cephalexin was higher in the complicated UTI group (19.3%) compared with the non-complicated UTI group (13.4%, p = 0.03). Notably, relatively low resistance rates were observed for ceftriaxone (4.4%) and gentamicin (6.0%). Over time, a significant decreasing trend in resistance to ampicillin was observed (slope = −0.0193, p = 0.011). No significant trends were found for trimethoprim–sulfamethoxazole, cephalexin, amoxicillin–clavulanic acid, ceftriaxone, and cefuroxime. Conclusions: Significant differences in pathogen distribution and resistance patterns between complicated UTI and non-complicated UTI groups highlight the need for continuous resistance monitoring and adherence to local guidelines. For the treatment of severe community F-UTI, ceftriaxone could be a reasonable option for first-onset F-UTI. Further studies are needed to implement antibiotic stewardship and optimize usage. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is a rare condition, typically seen in patients receiving antiresorptive or antiangiogenic drugs. This study aims to synthesize reports and case series of MRONJ regarding sociodemographic and clinical characteristics and to evaluate the effectiveness of the treatments applied. Following PRISMA guidelines, a search for case reports and case series was carried out in the PubMed-Medline database until March 2024. A total of 88 articles were included in this review, in a total of 151 cases. The key findings reveal that females were the most affected individuals (71% of the cases) with the average age at diagnosis being 66.27 years with a standard deviation of ±13.03. Stage 2 was the most observed stage, in 43% of cases, and zoledronic acid was the most commonly used drug (32% of cases). The oral route was the most common route of administration, in 26% of cases, with an average administration duration of 60.88 months (standard deviation ± 50.92). The mandible was the most commonly affected anatomical location (in 60% of cases). Amoxicillin + clavulanic acid (875 mg + 125 mg) and chlorhexidine (0.12%) were the most used antibiotics and mouthwash, with 16% and 26% of the cases, respectively. Surgical debridement was the most common surgical procedure, in 32% of cases, while the use of an L-PRF membrane was the most prevalent unconventional treatment, in 21% of cases. This study identified a statistically significant relationship between unconventional treatments and the cure of MRONJ (p < 0.001), indicating the need for further research to confirm these results. [ABSTRACT FROM AUTHOR]

Objectives: The use of cephalosporins combined with clavulanate for the treatment of ESBL-harbouring Enterobacteriaceae has been scarcely described. We aimed to describe the effect of different concentrations of clavulanate in the MIC of cefixime and ceftibuten of ESBL-producing Escherichia coli and Klebsiella pneumoniae. Methods: ESBL-producing E. coli and K. pneumoniae isolates were studied. Fixed concentrations of cefixime and ceftibuten (ranges of 32–0.25 and 64–0.5 ng/ml, respectively) were used. Combinations of cefixime/clavulanate and ceftibuten/clavulanate in different ratios (1:0, 1:1, 2:1, 4:1, 8:1, 16:1, 32:1) were tested. MIC were determined by broth microdilution. Results: A total of 6 ESBL-producing E. coli, 6 ESBL-producing K. pneumoniae and 2 control E. coli were tested. When different quantities of clavulanate were added to cefixime and ceftibuten, greater than two-fold decreases in the MIC were observed. When testing the 1:1 cefixime/clavulanate ratio, 10/12 isolates were susceptible. When the ratios 2:1, 4:1, 8:1 and 16:1 were tested, susceptibility was noted for 9/12, 8/12, 4/12 and 5/12 isolates, respectively. Only 2/12 K. pneumoniae isolates were susceptible when the ratio 32:1 was tested. When testing ceftibuten/clavulanate, all isolates remained susceptible across all experiments. Conclusions: Clavulanic acid has a favourable effect in reducing the MIC of cefixime and ceftibuten in isolates of ESBL-producing E. coli and K. pneumoniae. Combining clavulanate with ceftibuten or cefixime could be a useful treatment strategy.

The prevalence of antibiotic resistance has been demonstrated in various food-borne pathogens. Beta-lactam antibiotics are among the first-line antimicrobials that are normally administered in case of gastrointestinal infections. However, Escherichia coli (E. coli) and some other members of Enterobacteriaceae have indicated broad resistance against such antibiotics thanks to extended-spectrum beta-lactamase (ESBL) enzymes. In this research, 216 stool samples have been screened for ESBL-producing E. coli, using phenotypic antibiotic susceptibility tests. ESBL-producing E. coli isolates were further screened for the presence of antibiotic-resistance genes CTX-M, SHV, and TEM. Our isolation experiments resulted in 111 E. coli isolates among which 41 (36.9%) isolates were found as ESBL. Also, 51.2% of the above ESBL isolates harbored blaTEM. Furthermore, 18 (43.9%) and 2 (4.9%) of those ESBL isolates had blaCTX-M and blaSHV genes, respectively. Our results revealed a detectable prevalence of ESBL E. coli in stool samples collected during food outbreaks. Results of such researches can guide how to control the distribution of drug-resistant pathogens in various environments. In this line, the considerable prevalence of ESBL E. coli seems to have originated from the wide administration of various beta-lactam antibiotics.

AbstractOur previous clinical observations showed that platelet rich fibrin (PRF) can be used to deliver antibiotics to attenuate postoperative complications after unilaterally impacted mandibular third molar surgery (IMTMS). In order to begin understanding the mechanism involved in the beneficial in vivo effects of PRF-mediated delivery of antibiotics, in vitro studies were performed, which showed that PRF preparations containing amoxicillin/clavulanic acid or clindamycin significantly inhibited the growth of S. aureus bacteria. In our previous study, comparisons were made between control and treated groups. However, since variations among individual patients could possibly affect the results, the current study included patients with bilaterally symmetric impacted mandibular third molars, allowing us to compare control and antibiotic treatment within each patient. The effects of PRF preparations containing amoxicillin/clavulanic acid or clindamycin on IMTMS was tested in 60 clinical cases. Antibiotic-injected PRF treatment after bilaterally IMTMS resulted in significantly reduced pain, less use of analgesics, and reduced swelling and trismus compared to the control group (PRF without antibiotics) confirming our previous results after unilaterally IMTMS. The in vitro results support the hypothesis that in vivo delivery of antibiotics using PRF produces therapeutic effects after IMTMS by attenuating bacterial infection and inflammation. [ABSTRACT FROM AUTHOR]

The purpose of this in vitro study was to develop calcium sulfate (CS)-based disks infused with an antimicrobial drug, which can be used as a post-surgical treatment modality for osteomyelitis. CS powder was embedded with 10% antibiotic, amoxicillin (AMX) or moxifloxacin (MFX), to form composite disks 11 mm in diameter that were tested for their degradation and antibiotic release profiles. For the disk degradation study portion, the single drug-loaded disks were placed in individual meshes, subsequently submerged in phosphate-buffered saline (PBS), and incubated at 37 °C. The disks were weighed once every seven days and analyzed via Fourier-transform infrared spectroscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and scanning electron microscopy. During the antibiotic release analysis, composite disks were placed in PBS solution, which was changed every 3 days, and analyzed for antibiotic activity and efficacy. The antibacterial effects of these sustained-release composites were tested by agar diffusion assay using Streptococcus mutans (S. mutans) UA 159 as an indicator strain. The degradation data showed significant increases in the degradation of all disks with the addition of antibiotics. Following PBS incubation, there were significant increases in the amount of phosphate and decreases in the amount of sulfate. The agar diffusion assay demonstrated that the released concentrations of the respective antibiotics from the disks were significantly higher than the minimum inhibitory concentration exhibited against S. mutans over a 2–3-week period. In conclusion, CS-antibiotic composite disks can potentially serve as a resorbable, osteoconductive, and antibacterial therapy in the treatment of bone defects and osteomyelitis. [ABSTRACT FROM AUTHOR]