Underdiagnosis of Borderline oxacillin-resistant Staphylococcus aureus (BORSA) - Case series.

Borderline oxacillin-resistant Staphylococcus aureus (BORSA) are mecA-negative strains with oxacillin minimum inhibitor concentration (MIC) close to the resistance breakpoint of ≥ 4µg/mL. Instead of producing penicillin-binding protein with low affinity to methicillin (oxacillin) mediated by mecA gene as in methicillin-resistant S. aureus (MRSA), BORSA strains are characterised by the hyperproduction of ß-lactamase enzymes, thus able to break down methicillin. Common laboratory methods to detect MRSA such as cefoxitin disk diffusion alone may fail to detect methicillin resistance due to BORSA. We report five cases of BORSA blood-stream infections in a university teaching hospital. All isolates were found to be susceptible to cefoxitin using disk diffusion, resistant to oxacillin using automated MIC method, and did not harbour mecA gene. All patients were suscessfully treated with anti-MRSA antibiotics, and removal of primary sources were done if identified. A more cost-effective method for screening and diagnosis of BORSA is needed in addition to cefoxitin disk diffusion test, in order to monitor the spread, and to enable routine detection and treatment of this pathogen.

Cefoxitin versus carbapenems as definitive treatment for extended-spectrum ß-lactamase-producing Klebsiella pneumoniae bacteremia in intensive care unit: a propensity-matched retrospective analysis.

BACKGROUND: Despite cefoxitin's in vitro resistance to hydrolysis by extended-spectrum beta-lactamases (ESBL), treatment of ESBL-producing Klebsiella pneumoniae (KP) infections with cefoxitin remains controversial. The aim of our study was to compare the clinical efficacy of cefoxitin as definitive antibiotic therapy for patients with ESBL-KP bacteremia in intensive care unit, versus carbapenem therapy. METHODS: This retrospective study included all patients with monomicrobial bacteremia hospitalized in intensive care unit between January 2013 and January 2023 at the University Hospital of Guadeloupe. The primary outcome was the 30-day clinical success defined as a composite endpoint: 30-day survival, absence of relapse and no change of antibiotic therapy. Cox regression including a propensity score (PS) and PS-based matched analysis were performed for endpoint analysis. RESULTS: A total of 110 patients with bloodstream infections were enrolled. Sixty-three patients (57%) received definitive antibiotic therapy with cefoxitin, while forty-seven (43%) were treated with carbapenems. 30-day clinical success was not significantly different between patients treated with cefoxitin (57%) and carbapenems (53%, p = 0.823). PS-adjusted and PS-matched analysis confirmed these findings. Change of definitive antibiotic therapy was more frequent in the cefoxitin group (17% vs. 0%, p = 0.002). No significant differences were observed for the other secondary endpoints. The acquisition of carbapenem-resistant Pseudomonas aeruginosa was significantly higher in patients receiving carbapenem therapy (5% vs. 23%, p = 0.007). CONCLUSIONS: Our results suggest that cefoxitin as definitive antibiotic therapy could be a therapeutic option for some ESBL-KP bacteremia, sparing carbapenems and reducing the selection of carbapenem-resistant Pseudomonas aeruginosa strains.

Profiling of antibiotic resistance among uropathogens isolated from patients attending Kericho County Referral Hospital.

Introduction: urinary tract infection (UTI) comes second after respiratory infections in most communities and hospital settings, affecting people of all ages. Frequent use of antibiotics to manage UTI has resulted in development of resistance, calling upon policymakers to fast-track and enforce policies that guide the use of antibiotics in the country. This study intended to determine the current antibiotic resistance to uropathogens among patients attending Kericho County Referral Hospital. Methods: three hundred urine samples from eligible participants were cultured and bacteria colonies identified using biochemical tests. Antibiotic sensitivity was done using Kirby Bauer disk diffusion method on Mueller Hinton Agar. Results: the aetiological agents of UTI were Staphylococcus aureus, Enterococci faecalis, E. coli, Proteus spp and Klebsiella pneumonia. Antibiotic resistance was observed among these uropathogens to commonly used antibiotics namely; ampicillin (84.3%), azithromycin (71.9%) and augmentin (69.8%). However, there were some bacteria that were susceptible to all or some commonly used antibiotics. There was moderate resistance to norfloxacin (43%) except in Staphylococcus aureus which showed 64% resistance. The isolates showed less resistance to cefoxitine (13.2%), gentamycin (11.6%) and ciprofloxacin (10%). While most bacteria showed multiple resistance to 3 drugs, some showed resistance to at most 5 drugs tested in the study. Conclusion: this study found Staphylococcus aureus to be the predominant aetiological agent of UTI. Cefoxitine, gentamycin and ciprofloxacin are good therapeutic choices for confirmed recurrent UTI when culture results are unavailable. There is need to have regular screening of aetiological agents of UTI and their resistance to antimicrobials.

Association Between Biliary Pathogens, Surgical Site Infection, and Pancreatic Fistula: Results of a Randomized Trial of Perioperative Antibiotic Prophylaxis in Patients Undergoing Pancreatoduodenectomy.

OBJECTIVE: To establish the association between bactibilia and postoperative complications when stratified by perioperative antibiotic prophylaxis. BACKGROUND: Patients undergoing pancreatoduodenectomy experience high rates of surgical site infection (SSI) and clinically relevant postoperative pancreatic fistula (CR-POPF). Contaminated bile is known to be associated with SSI, but the role of antibiotic prophylaxis in mitigation of infectious risks is ill-defined. METHODS: Intraoperative bile cultures (IOBCs) were collected as an adjunct to a randomized phase 3 clinical trial comparing piperacillin-tazobactam with cefoxitin as perioperative prophylaxis in patients undergoing pancreatoduodenectomy. After compilation of IOBC data, associations between culture results, SSI, and CR-POPF were assessed using logistic regression stratified by the presence of a preoperative biliary stent. RESULTS: Of 778 participants in the clinical trial, IOBC were available for 247 participants. Overall, 68 (27.5%) grew no organisms, 37 (15.0%) grew 1 organism, and 142 (57.5%) were polymicrobial. Organisms resistant to cefoxitin but not piperacillin-tazobactam were present in 95 patients (45.2%). The presence of cefoxitin-resistant organisms, 92.6% of which contained either Enterobacter spp. or Enterococcus spp., was associated with the development of SSI in participants treated with cefoxitin [53.5% vs 25.0%; odds ratio (OR)=3.44, 95% CI: 1.50-7.91; P =0.004] but not those treated with piperacillin-tazobactam (13.5% vs 27.0%; OR=0.42, 95% CI: 0.14-1.29; P =0.128). Similarly, cefoxitin-resistant organisms were associated with CR-POPF in participants treated with cefoxitin (24.1% vs 5.8%; OR=3.45, 95% CI: 1.22-9.74; P =0.017) but not those treated with piperacillin-tazobactam (5.4% vs 4.8%; OR=0.92, 95% CI: 0.30-2.80; P =0.888). CONCLUSIONS: Previously observed reductions in SSI and CR-POPF in patients that received piperacillin-tazobactam antibiotic prophylaxis are potentially mediated by biliary pathogens that are cefoxitin resistant, specifically Enterobacter spp. and Enterococcus spp.

Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial.

Importance: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood. Objective: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics. Design, Setting, and Participants: Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment. Intervention: The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care). Main Outcomes and Measures: The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program. Results: The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32). Conclusions and Relevance: In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT03269994.

Epidemiology of clinically isolated methicillin-resistant Staphylococcus aureus (MRSA) and its susceptibility to linezolid and vancomycin in Egypt: a systematic review with meta-analysis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen that causes severe morbidity and mortality worldwide. For the establishment of national strategies to combat MRSA infection in each country, accurate and current statistics characterizing the epidemiology of MRSA are essential. The purpose of this study was to determine the prevalence of MRSA among Staphylococcus aureus clinical isolates in Egypt. In addition, we aimed to compare different diagnostic methods for MRSA and determine the pooled resistance rate of linezolid and vancomycin to MRSA. To address this knowledge gap, we conducted a systematic review with meta-analysis. METHODS: A comprehensive literature search from inception to October 2022 of the following databases was performed: MEDLINE [PubMed], Scopus, Google Scholar, and Web of Science. The review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement. Based on the random effects model, results were reported as proportions with a 95% confidence interval (CI). Analyses of the subgroups were conducted. A sensitivity analysis was conducted to test the robustness of the results. RESULTS: A total of sixty-four (64) studies were included in the present meta-analysis, with a total sample size of 7171 subjects. The overall prevalence of MRSA was 63% [95% CI: 55-70]. Fifteen (15) studies used both PCR and cefoxitin disc diffusion for MRSA detection, with a pooled prevalence rate of 67% [95% CI: 54-79] and 67% [95% CI: 55-80], respectively. While nine (9) studies used both PCR and Oxacillin disc diffusion for MRSA detection, the pooled prevalences were 60% [95% CI: 45-75] and 64% [95% CI: 43-84], respectively. Furthermore, MRSA appeared to be less resistant to linezolid than vancomycin, with a pooled resistance rate of 5% [95% CI: 2-8] to linezolid and 9% [95% CI: 6-12] to vancomycin, respectively. CONCLUSION: Our review highlights Egypt's high MRSA prevalence. The cefoxitin disc diffusion test results were found to be consistent with PCR identification of the mecA gene. A prohibition on antibiotic self-medication and efforts to educate healthcare workers and patients about the proper use of antimicrobials may be required to prevent further increases.

Piperacillin/tazobactam versus cefepime or carbapenems for cefoxitin-non-susceptible Enterobacter cloacae, Klebsiella aerogenes, Citrobacter freundii, Serratia marcescens and Morganella morganii bacteraemia in immunocompromised patients.

BACKGROUND: The role of piperacillin/tazobactam for treatment of serious infections due to AmpC-producing organisms remains debatable, particularly in immunocompromised patients. METHODS: This was a retrospective cohort study in immunocompromised patients that investigated the effect of definitive treatment with either piperacillin/tazobactam versus cefepime or carbapenems for bacteraemia caused by cefoxitin-non-susceptible Enterobacterales. The primary endpoint was a composite of clinical and microbiological failure. A logistic regression model was constructed to assess the impact of definitive treatment choice on the primary endpoint. RESULTS: A total of 81 immunocompromised patients with blood cultures positive for cefoxitin-non-susceptible Enterobacterales were included for analysis. There was more microbiological failure in the piperacillin/tazobactam arm compared with the cefepime/carbapenem arm (11.4% versus 0.0%, P = 0.019). Definitive treatment with cefepime or a carbapenem was associated with a decreased odds of clinical or microbiological failure (OR 0.303, 95% CI 0.093-0.991, P = 0.048) when controlling for baseline characteristics. CONCLUSIONS: In immunocompromised patients with bacteraemia due to cefoxitin-non-susceptible Enterobacterales, definitive treatment with piperacillin/tazobactam was associated with an increased risk of microbiological failure and higher odds of clinical or microbiological failure compared with cefepime or carbapenems.

MIC Discrepancies between Parenteral and Oral Anti-Staphylococcal Beta-Lactams among MSSA.

INTRODUCTION: Recent evidence has shown that oral antibiotic therapy is not inferior to IV antibiotic therapy in the treatment of complicated Staphylococcus aureus infections. Therefore, oral antibiotic therapy is now frequently prescribed in clinical practice due to cost benefit, ease of administration, decreased complication rate, and lack of need for IV access. In vitro susceptibility testing for ß-lactam oral antibiotics is not routinely performed as the guidelines provided by the Clinical and Laboratory Standards Institute (CLSI) recommend using oxacillin and cefoxitin as surrogate markers. Hence, oral antibiotic susceptibilities for cephalexin and dicloxacillin are not reported and implied based on oxacillin and cefoxitin. The objective of the current study was to determine whether susceptibilities among S. aureus isolates are predictable when comparing commonly used IV and oral beta-lactams. METHODS: Cefazolin, cephalexin, dicloxacillin, and oxacillin broth microdilution minimum inhibitory concentrations (MICs) were determined for 100 clinical isolates of methicillin-sensitive S. aureus by broth microdilution following CLSI guidelines. RESULTS: Among these isolates, median MICs for cephalexin were eight-fold higher than cefazolin MICs and median MICs for dicloxacillin were four-fold less than oxacillin MICs. Ten percent of more strains studied had a major or very major error in its susceptibility reporting when cephalexin was compared to its surrogate marker oxacillin. DISCUSSIONS/CONCLUSIONS: The variations in MICs observed compounded with the dosing and pharmacokinetic differences of oral versus IV ß-lactam suggests that establishing breakpoints for oral ß-lactam antibiotics is necessary to ensure adequate therapy is selected for the treatment of complex S. aureus infections.

Antimicrobial susceptibility and minimum inhibitory concentration distribution of common clinically relevant non-tuberculous mycobacterial isolates from the respiratory tract.

Objective: To determine the minimum inhibitory concentration (MIC) distribution of antibacterial drugs and the susceptibility of non-tuberculous mycobacterial (NTM) isolates to provide a reference basis for the clinical selection of an effective starting regimen.Methods: The common clinical isolates of NTM in the respiratory tract, which met the standards of the American Thoracic Society for NTM lung disease, were collected. The MICs of 81 isolates were determined using the microbroth dilution method (Thermo Fisher Scientific, USA), as recommended by the Clinical and Laboratory Standards Institute, USA.Results: Included were 43 Mycobacterium avium complex (MAC) strains, 24 M. abscessus complex (MAB) strains, and 14 M. kansasii strains. The sensitivity rates of MAC to clarithromycin and amikacin were 81.4% and 79.1%, respectively, while the sensitivity rates to linezolid and moxifloxacin were only 20.9% and 9.3%; the MIC of rifabutin was the lowest (MIC50% was just 2 µg/mL). After incubation for 3-5 days, the sensitivity rate of MAB to clarithromycin was 87.5%; this decreased to 50% after 14 days' incubation. Most of them were susceptible to amikacin (91.6%), and most were resistant to moxifloxacin (95.8%), ciprofloxacin (95.8%), imipenem (95.8%), amoxicillin/clavulanate (95.8%), tobramycin (79.1%), doxycycline (95.8%) and trimethoprim/sulfamethoxazole (95.8%). intermediate (83.3%) and resistant (16.7%) to cefoxitin. The susceptibility to linezolid was only 33.3%. The sensitivity and resistance breakpoints of tigecycline were set to ≤0.5 and ≥8 µg/mL, respectively, and the sensitivity and resistance rates were 50% and 0%, respectively. M. kansasii was susceptible to clarithromycin, amikacin, linezolid, moxifloxacin, rifampicin and rifabutin (100%).Discussion: In Wenzhou, clarithromycin, amikacin and rifabutin have good antibacterial activity against MAC, while linezolid and moxifloxacin have high resistance. Amikacin and tigecycline have strong antibacterial activity against MAB, while most other antibacterial drugs are resistant to varying degrees. Most antibacterial drugs are susceptible to M. kansasii and have good antibacterial activity.Conclusion: The identification of NTM species and the detection of their MICs have certain guiding values for the treatment of NTM lung disease.Key MessageThe three most common respiratory non-tuberculous mycobacterial (NTM) isolates with clinical significance in the Wenzhou area were tested for drug susceptibility. The broth microdilution method was used to determine the minimum inhibitory concentration distribution of antibacterial drugs and the susceptibility of NTM isolates to provide a reference basis for the clinical selection of an effective starting regimen.

Cefoxitin-based combination for ESBL-producing Enterobacteriaceae endocarditis.

BACKGROUND: Endocarditis due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is a rare but challenging condition. Its treatment relies on carbapenems alone or in combination, and no alternative has been described to date. The cephamycin cefoxitin has been used for treatment of mild ESBL-producing Enterobacteriaceae infections. CASE PRESENTATION: We report two patients with nosocomial endocarditis due to ESBL-producing Escherichia coli and Klebsiella pneumoniae who underwent clinical failure or adverse event, respectively, during treatment with imipenem-cilastatin. The first patient was subsequently treated with cefoxitin combined with ciprofloxacin with a favorable outcome. In the second patient, the endocarditis relapsed following a 6-week treatment with cefoxitin and fosfomycin. In time-kill assays, the cefoxitin/ciprofloxacin and cefoxitin/fosfomycin combinations showed synergistic effect. CONCLUSION: These cases illustrate that cefoxitin is an interesting alternative to carbapenems, even in severe infections such as endocarditis. Pharmacokinetic optimization and combination with another synergistic antibiotic should be considered whenever possible.

Drug repurposing strategy: An emerging approach to identify potential therapeutics for treatment of bovine mastitis.

The current study was designed to characterize methicillin-resistant Staphylococcus aureus (MRSA) isolated from bovine milk, along with its response to antibiotics, and ultimately reverse its mechanism of resistance by modulation with non-antibiotics. The synergistic combination of antibiotics with NSAIDs were tested in-vivo by giving MRSA challenge to rabbits. The current study reported an overall 23.79% prevalence of MRSA. The BLAST alignment of current study sequences revealed 99% similarity with mecA gene of MRSA from NCBI database. The current study isolates were more similar to each other and also with reference sequences as compared to other mecA gene sequences from Turkey, India, and Russia. Antibiogram of MRSA isolates showed a highly resistant response to cefoxitin, amoxicillin, and gentamicin. Amoxicillin, gentamicin, tylosin, vancomycin, and ciprofloxacin elicited a significant response (p < 0.05) in combination with non-antibiotics against tested MRSA isolates. The highest zone of inhibition (ZOI) increase was noted for vancomycin in combination with flunixin meglumine (145.45%) and meloxicam (139.36%); gentamicin with flunixin meglumine (85.71%) and ciprofloxacin with ivermectin (71.13%). Synergistic behavior was observed in the combination of gentamicin with ketoprofen; sulfamethoxazole and oxytetracycline with meloxicam. Hematological analysis showed significant differences (p < 0.05) among lymphocyte count and bilirubin. On histopathological examination of skin tissue, hyperplasia of epithelium, sloughed off epidermis, hyperkeratosis, infiltration of inflammatory cells, and hemorrhages were observed. The highest cure rate was observed in case of gentamicin in combination with ketoprofen as compared to other treatment groups. The current study concluded antibiotics in combination with non-antibiotics as potential therapeutic agents for resistance modulation against MRSA. This study will help to devise treatment and control strategies against bovine mastitis. Although the prospect of using NSAIDs to manage infections caused by MRSA appears to be a promising direction, further studies should be conducted to test these medications using suitable in-vivo models in controlled clinical trials to justify their repurposing as a treatment for MRSA infections.

Comparative Genomics of Borderline Oxacillin-Resistant Staphylococcus aureus Detected during a Pseudo-outbreak of Methicillin-Resistant S. aureus in a Neonatal Intensive Care Unit.

Active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) is a component of our neonatal intensive care unit (NICU) infection prevention efforts. Recent atypical trends prompted review of 42 suspected MRSA isolates. Species identification was confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and methicillin resistance was reevaluated by PBP2a lateral flow assay, cefoxitin/oxacillin susceptibility testing, mecA and mecC PCR, and six commercially available MRSA detection agars. All isolates were confirmed S. aureus, but only eight were MRSA (cefoxitin resistant, PBP2a positive, mecA positive, growth on all MRSA screening agars). One MRSA isolate was cefoxitin susceptible but PBP2a and mecA positive, and the remaining 33 were cefoxitin susceptible, PBP2a negative, and mecA negative; interestingly, these isolates grew inconsistently across MRSA screening agars and had susceptibility profiles consistent with that of borderline oxacillin-resistant S. aureus (BORSA). Comparative genomic analyses found these BORSA isolates to be phylogenetically diverse and not representative of clonal expansion or shared gene content, though clones of two NICU strains were infrequently observed over 8 months. We identified 6 features-substitutions and truncations in PBP2, PBP4, and GdpP and beta-lactamase hyperproduction-that were used to generate a random forest classifier to distinguish BORSA from methicillin-susceptible S. aureus (MSSA) in our cohort. Our model demonstrated a robust ability to predict the BORSA phenotype among isolates collected across two continents (validation area under the curve [AUC], 0.902). Taking these findings together, we observed an unexpected prevalence of BORSA in our NICU, BORSA misclassification by existing MRSA screening methods, and markers that are together discriminatory for BORSA and MSSA within our cohort. This work has implications for epidemiological reporting of MRSA rates for centers using different screening methods. IMPORTANCE In this study, we found a high prevalence of Staphylococcus aureus isolates exhibiting a borderline oxacillin resistance phenotype (BORSA) in our neonatal intensive care unit (NICU) serendipitously due to the type of MRSA screening agar used by our laboratory for active surveillance cultures. Subsequent phenotypic and molecular characterization highlighted an unexpected prevalence and variability of BORSA isolates. Through whole-genome sequencing, we interrogated core and accessory genome content and generated a random forest classification model to identify mutations and truncations in the PBP2, PBP4, and GdpP proteins and beta-lactamase hyperproduction, which correlated with BORSA and MSSA phenotypes among S. aureus clinical isolates collected across two continents. In consideration of these findings, this work will help clinical microbiology laboratories and clinicians identify MRSA screening shortfalls and draw attention to the non-mecA-mediated BORSA phenotype.

Ampicillinase C Beta-lactamase Producers among Isolates of Enterobacteriaceae in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Ampicillinase C beta-lactamase-producing organisms are often resistant to multiple antimicrobial agents, and therapeutic options against these pathogens are limited. Limited information is available regarding Ampicillinase C beta-lactamase producers. The aim of this study was to find out the prevalence of Ampicillinase C beta-lactamase producers among isolates of Enterobacteriaceae in a tertiary care centre. Methods: A descriptive cross-sectional study was carried out in the Clinical Microbiology Laboratory of a tertiary care centre from May 2021 to October 2021. Ethical approval was received from the Institutional Review Committee (Reference number: 044-077/078). Isolates of Enterobacteriaceae from various clinical samples were collected by convenience sampling. Ampicillinase C screening for beta-lactamase producers among the Enterobacteriaceae isolates was done using cefoxitin (30 µg) disc. Detection of Ampicillinase C beta-lactamase producers among the screen-positive isolates was done by cefoxitin-cloxacillin double-disc synergy test. An increase in the zone size of ≥4 mm was considered as Ampicillinase C beta-lactamase producers. Point estimate and 95% Confidence Interval were calculated. Results: Among the total 481 isolates of Enterobacteriaceae, 49 (10.19%) (7.50-12.90, 95 % Confidence Interval) were detected as Ampicillinase C beta-lactamase producers among isolates of Enterobacteriaceae. Conclusions: The prevalence of Ampicillinase C beta-lactamase producers was lower than in other studies done in similar settings. Meropenem could be a drug of choice for the treatment of infections due to Ampicillinase C beta-lactamase-producing gram-negative bacteria. Keywords: antibiotic; beta-lactamase; Enterobacteriaceae; gram-negative bacteria.

Cefoxitin versus piperacillin-tazobactam as surgical antibiotic prophylaxis in patients undergoing pancreatoduodenectomy: protocol for a randomised controlled trial.

INTRODUCTION: Although antibiotic prophylaxis is established in reducing postoperative surgical site infections (SSIs), the optimal antibiotic for prophylaxis in pancreatoduodenectomy (PD) remains unclear. The study objective is to evaluate if administration of piperacillin-tazobactam as antibiotic prophylaxis results in decreased 30-day SSI rate compared with cefoxitin in patients undergoing elective PD. METHODS AND ANALYSIS: This study will be a multi-institution, double-arm, non-blinded randomised controlled superiority trial. Adults ≥18 years consented to undergo PD for all indications who present to institutions participating in the National Surgical Quality Improvement Program Hepato-Pancreato-Biliary (NSQIP HPB) Collaborative will be included. Data collection will use the NSQIP HPB Collaborative Surgical Clinical Reviewers. Patients will be randomised to either 1-2 g intravenous cefoxitin or 3.375-4.5 g intravenous piperacillin-tazobactam within 60 min of surgical incision. The primary outcome will be 30-day postoperative SSI rate following PD. Secondary outcomes will include 30-day postoperative mortality; specific postoperative complication rate; and unplanned reoperation, length of stay, and hospital readmission. A subset of patients will have bacterial isolates and sensitivities of intraoperative bile cultures and SSIs. Postoperative SSIs and secondary outcomes will be analysed using logistic regression models with the primary predictor as the randomised treatment group. Additional adjustment will be made for preoperative biliary stent presence. Additionally, bacterial cultures and isolates will be summarised by presence of bacterial species and antibiotic sensitivities. ETHICS AND DISSEMINATION: This study is approved by the Institutional Review Board at Memorial Sloan Kettering Cancer Center. This trial will evaluate the effect of piperacillin-tazobactam compared with cefoxitin as antibiotic prophylaxis on the hazard of postoperative SSIs. The results will be disseminated regardless of the effect of the intervention on study outcomes. The manuscript describing the effect of the intervention will be submitted to a peer-reviewed journal when data collection and analyses are complete. TRIAL REGISTRATION NUMBER: NCT03269994.

How to optimize administration of cefoxitin for the treatment of extended spectrum producing Enterobacteriaceae-related infection?

Pharmacological and clinical data regarding cefoxitin for the treatment of ESBL-producing Enterobacteriaceae-related infections are limited. We performed a multicentric prospective cohort study to evaluate continuous/prolonged, or intermittent infusion of cefoxitin. We assessed the plasma concentration as a function of the duration of infusion and then performed a simulation of the percentage of patients who would reach the PK/PD targets, set at 100% ƒT> MIC or 100% ƒT>4 MIC. Eighty-one patients were included. All patients were treated with 6 gr./day. MICs to cefoxitin ranged from 0.5 to 64 mg/L. Sixteen (19.7%) patients were infected with strains with cefoxitin MICs ≥ 8 mg/L. In all patients infected with strains with MICs ≤ 6 mg/L, PK/PD objectives (100% ƒT> MIC) were achieved with prolonged or continuous infusion. In contrast, when MICs were 8 mg/L only, continuous infusion was sufficient to achieve the PK/PD objectives (100% ƒT> MIC). Extended infusion of cefoxitin is necessary for the treatment of non-UTI ESBL-related infections.

Ceftriaxone Combined With Metronidazole is Superior to Cefoxitin Alone in the Management of Uncomplicated Appendicitis in Children: Results from a Multicenter Collaborative Comparative Effectiveness Study.

OBJECTIVE: To compare rates of surgical site infection between the 2 most commonly utilized narrow-spectrum antibiotic regimens in children with uncomplicated appendicitis (ceftriaxone with metronidazole and cefoxitin alone). SUMMARY OF BACKGROUND DATA: Narrow-spectrum antibiotics have been found to be equivalent to extended-spectrum (antipseudomonal) agents in preventing surgical site infection (SSI) in children with uncomplicated appendicitis. The comparative effectiveness of different narrow-spectrum agents has not been reported. METHODS: This was a multicenter retrospective cohort study using clinical data from the Pediatric National Surgical Quality Improvement Program Appendectomy Collaborative Pilot database merged with antibiotic utilization data from the Pediatric Health Information System database from January 2013 to June 2015. Multivariable logistic regression was used to compare outcomes between antibiotic treatment groups after adjusting for patient characteristics, surrogate measures of disease severity, and clustering of outcomes within hospitals. RESULTS: Eight hundred forty-six patients from 14 hospitals were included in the final study cohort with an overall SSI rate of 1.3%. A total of 56.0% of patients received ceftriaxone with metronidazole (hospital range: 0%-100%) and 44.0% received cefoxitin (range: 0%-100%). In the multivariable model, ceftriaxone with metronidazole was associated with a 90% reduction in the odds of a SSI compared to cefoxitin [0.2% vs 2.7%; odds ratio: 0.10 (95% confidence interval 0.02-0.60); P = 0.01]. CONCLUSIONS: Ceftriaxone combined with metronidazole is superior to cefoxitin alone in preventing SSIs in children with uncomplicated appendicitis.