Cefoxitin for Intra-amniotic Infections and Endometritis: A Retrospective Comparison to Traditional Antimicrobial Therapy Regimens Within a Healthcare System.

BACKGROUND: Local institutional guidelines and order sets were updated in June 2023 to recommend first-line cefoxitin monotherapy for the treatment of intra-amniotic infections (IAIs) and endometritis. This study evaluated the clinical impact of this change. METHODS: This was a retrospective, observational cohort study in an 11-campus health system comparing clinical outcomes of patients with chorioamnionitis, endometritis, or septic abortion receiving intravenous antimicrobial therapy before and after implementation of first-line cefoxitin monotherapy recommendations for the treatment of these infections. Primary outcome was a composite of serious clinical events postdelivery (ie, intensive care unit admission, death, hospital readmission related to IAI or endometritis within 30 days, additional surgery or procedures, or deep surgical site infection). Baseline characteristics between the pre- and post-cefoxitin groups were compared via Student's t tests for continuous variables and chi-square tests for categorical variables. Outcomes were evaluated via generalized linear modeling. RESULTS: A total of 472 patients were enrolled, 350 (74%) in the pre-cefoxitin group and 122 (26%) in the post-cefoxitin group. Groups were significantly different by race, healthcare payor, and hospital campus. Cefoxitin was rarely used in the pre-cefoxitin group (n = 2, <0.1%) and commonly used in the post-cefoxitin group (n = 112, 91.8%). After controlling for group differences, odds of experiencing serious clinical event postdelivery in the post-cefoxitin group were noninferior to those in the pre-cefoxitin group (adjusted odds ratio, .37; 95% CI, .17-.76; P = .010). CONCLUSIONS: Local institutional guidelines with predominant use of cefoxitin therapy were noninferior to traditional antimicrobial therapy regimens for the treatment of IAI.

In vitro activity of cefoxitin, imipenem, meropenem, and ceftaroline in combination with vaborbactam against Mycobacterium abscessus.

Mycobacterium abscessus (MAB) infections pose a growing public health threat. Here, we assessed the in vitro activity of the boronic acid-based ß-lactamase inhibitor, vaborbactam, with different ß-lactams against 100 clinical MAB isolates. Enhanced activity was observed with meropenem and ceftaroline with vaborbactam (1- and >4-fold MIC50/90 reduction). CRISPRi-mediated blaMAB gene knockdown showed a fourfold MIC reduction to ceftaroline but not the other ß-lactams. Our findings demonstrate vaborbactam's potential in combination therapy against MAB infections.

Comparing cefazolin/ metronidazole, piperacillin-tazobactam, or c efoxitin as surgical antibiotic prophylaxis in patients undergoing pancreaticoduodenectomy: A retrospective cohort study.

BACKGROUND: Preoperative antibiotic options for pancreaticoduodenectomy (PD) include cefoxitin (CX), piperacillin-tazobactam (PT), or combined cefazolin and metronidazole (CM). Recent studies suggest the superiority of PT over CX, but evidence for CM is unclear. OBJECTIVE: To explore the impact of preoperative antibiotic selection (CM vs. PT and CX vs. PT) on the development of surgical site infections (SSI). METHODS: Consecutive adult patients at one institution who underwent PD from November 2017 to December 2021 and received either CM, PT, or CX preoperatively, were included. The primary outcome was SSI. Secondary outcomes included postoperative infections and clinically significant postoperative pancreatic fistula (POPF). Logistic regression models were used. RESULTS: Among 127 patients included in the study, PT, CM, and CX were administered in 46 (36.2%), 44 (34.6%), and 37 (29.4%) patients, respectively. There were 32 (27.1%) SSI, 20 (36.1%) infections, and 21 (22.9%) POPF events. PT use was associated with reduced risk of SSI compared to CX (OR: 0.32, 95% CI: 0.11-0.89, p = 0.03), but there was no difference as compared to CM (OR: 0.75, 95% CI: 0.27-2.13, p = 0.59). There were no differences in secondary outcomes. CONCLUSION: PT reduced SSI rates compared to CX but was no different to CM among patients undergoing PD at our center.

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.

In vitro efficacy of humanized regimen of flomoxef against extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

This study compared the efficacy of flomoxef with other ß-lactam antibiotics against extended-spectrum ß-lactamases (ESBL)-producing bacteria of clinical relevance. First, the prevalence and ß-lactamase genotypes of ESBL-producing strains among Escherichia coli and Klebsiella pneumoniae isolates collected in Japan from 2004 to 2018 were investigated. High MIC90 values (>64 µg/mL) of ceftriaxone, cefepime, and ceftazidime and low MIC90 values (≤0.06-2 µg/mL) of flomoxef, cefmetazole, and meropenem against both species were observed. Second, a chemostat model was used to analyze the efficacy of humanized regimens of three oxacephem/cephamycin antibiotics (flomoxef, cefmetazole, cefoxitin) and two other antibiotics (meropenem and piperacillin/tazobactam) in suppressing the growth of five ESBL-producing E. coli and two K. pneumoniae strains. Flomoxef, piperacillin/tazobactam, and meropenem showed good bactericidal effects with >4 log10 CFU/mL reduction without bacterial regrowth at 24 h even when the MIC of test isolates was >MIC90. Cefmetazole and cefoxitin resulted in regrowth of test isolates with MIC ≥MIC90 at 24 h. Cefmetazole, cefoxitin, flomoxef, and meropenem showed increased MICs for regrown samples. A clear relationship between the proportion of time that the free drug concentration exceeded the MIC (%fT>MIC) and antibiotic efficacy was found for flomoxef, cefoxitin, and cefmetazole, and flomoxef had the highest %fT>MIC, whereas discrepancies between Clinical and Laboratory Standards Institute breakpoint and bactericidal activity were observed for cefmetazole. Flomoxef was effective in preventing the growth of all ESBL-producing strains, even those with an MIC eight times the MIC90. Thus, flomoxef may be a good alternative to meropenem in context of carbapenems sparing stewardship.

Association Between Antibiotic Redosing Before Incision and Risk of Incisional Site Infection in Children With Appendicitis.

OBJECTIVE: To evaluate whether redosing antibiotics within an hour of incision is associated with a reduction in incisional surgical site infection (iSSI) in children with appendicitis. BACKGROUND: Existing data remain conflicting as to whether children with appendicitis receiving antibiotics at diagnosis benefit from antibiotic redosing before incision. METHODS: This was a multicenter retrospective cohort study using data from the Pediatric National Surgical Quality Improvement Program augmented with antibiotic utilization and operative report data obtained though supplemental chart review. Children undergoing appendectomy at 14 hospitals participating in the Eastern Pediatric Surgery Network from July 2016 to June 2020 who received antibiotics upon diagnosis of appendicitis between 1 and 6 hours before incision were included. Multivariable logistic regression was used to compare odds of iSSI in those who were and were not redosed with antibiotics within 1 hour of incision, adjusting for patient demographics, disease severity, antibiotic agents, and hospital-level clustering of events. RESULTS: A total of 3533 children from 14 hospitals were included. Overall, 46.5% were redosed (hospital range: 1.8%-94.4%, P <0.001) and iSSI rates were similar between groups [redosed: 1.2% vs non-redosed: 1.3%; odds ratio (OR) 0.84, (95%,CI, 0.39-1.83)]. In subgroup analyses, redosing was associated with lower iSSI rates when cefoxitin was used as the initial antibiotic (redosed: 1.0% vs nonredosed: 2.5%; OR: 0.38, (95% CI, 0.17-0.84)], but no benefit was found with other antibiotic regimens, longer periods between initial antibiotic administration and incision, or with increased disease severity. CONCLUSIONS: Redosing of antibiotics within 1 hour of incision in children who received their initial dose within 6 hours of incision was not associated with reduction in risk of incisional site infection unless cefoxitin was used as the initial antibiotic.

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 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.

Staphylococcus aureus in cow milk and milk products in Ambo and Bako towns, Oromia, Ethiopia: prevalence, associated risk factors, hygienic quality, and antibiogram.

BACKGROUND: Staphylococcus aureus (S. aureus) is a foodborne bacterial pathogens that can cause staphylococcal food poisoning and contaminate food of animal origin worldwide. The current study was conducted to estimate the prevalence and assess risk factors, hygienic quality, and antibiogram of S. aureus in raw milk and milk products of cows in Ambo and Bako towns, Ethiopia. RESULTS: The overall prevalence of S. aureus in milk and milk products was 15.6% (94/601) with the highest prevalence in bulk tank raw milk (17.50%) and the lowest in "Ergo" (13.11%). High S. aureus contamination at farm level were associated with poor farm hygiene, extensive management system, medium farm size, loose housing, and less frequent removal of bedding. At the cow level, a high S. aureus isolation rate was observed in crossbred cows; cows with age equal to or greater than 5 years old, tick infestation, history of mastitis treatment, and udder washing were not practiced before milking. On the other hand, the type of container, hygiene of milk handler, and container were the major risk factors for bulk tank milk contamination with S. aureus. S. aureus counts ranging from 1.25 × 104 to 1.92 × 104 CFU/mL were detected in 28.33% of the bulk tank milk samples.. Antimicrobial susceptibility test showed higher resistance of S. aureus to amoxicillin (98.48%), oxacillin (98.48%), ampicillin (98.48%), cefoxitin (92.42%), and tetracycline (83.33%), with 43.94% of isolates showing multidrug resistance (MDR). The high prevalence of oxacillin and cefoxitin-resistant isolates, which is a possible indicator of the existence of methicillin-resistant Staphylococcus aureus (MRSA), was also noted in the current study. CONCLUSION: Higher prevalence of S. aureus and MDR isolates in milk and milk products was detected in study areas. Therefore, to make milk and milk products safe for human consumption, hygienic handling of milk and milk products, regular surveillance of antimicrobial resistance, and prudent use of drugs are recommended.

Assessment of glomerular filtration and tubular secretion in baboons with life-supporting pig kidney grafts.

With pig kidney xenotransplantation nearing clinical reality, it is imperative to measure pig kidney function in the graft recipients. Our aims were (i) to compare inulin clearance after a short intravenous (IV) bolus with steady-state inulin IV infusion, (ii) to use this method to measure the glomerular filtration rate (GFR), and (iii) to determine the tubular secretory function using cefoxitin in a pig-to-baboon renal transplant model. A short IV infusion of inulin and cefoxitin were followed by a maintenance IV infusion of inulin over 5 h in seven healthy baboons, three healthy pigs, and five baboons after bilateral native nephrectomy and intra-abdominal pig renal transplantation. Blood and urine samples were collected. Serum and urinary inulin and serum cefoxitin concentrations measured by validated assays were used to calculate GFR and renal secretion. GFR calculated were similar by both methods. The body weight normalized total body clearance of inulin was similar in pigs and baboons despite differences in absolute clearances. Pig kidney transplanted into baboons provided similar clearance in baboons when normalized to baboon body weight and sustained filtration and secretory functions. The study documented that pig kidneys support the physiologic needs of baboons and are likely to support human recipients as well.

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.

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.

Brazilian red propolis in combination with ß-lactams exerts an efficient antibacterial action over methicillin-resistant Staphylococcus aureus (MRSA) strains.

AIMS: The antibacterial activity of red propolis extract (RPE) and brown propolis extracts (BPE) and the synergistic effect of RPE with cefoxitin (CEFO), imipenem (IMI), and ertapenem (ERTA) was evaluated in vitro against methicillin-resistant Staphylococcus aureus (MRSA) strains. METHODS AND RESULTS: MRSA ATCC 33591, community-associated (CA-MRSA) USA300, and four clinical isolates were used. A broth microdilution assay was performed to obtain inhibitory and bactericidal concentrations of BPE, RPE, CEFO, IMI, and ERTA. RPE in combination with CEFO, IMI, and ERTA was evaluated on the formation or eradication of biofilm. The bacterial relative membrane conductivity of the strains was assessed after RPE and combinations exposition. Surface/binding computational analyzes between RPE compounds and penicillin binding protein 2a (PBP2a) were performed. BPE samples had no activity against MRSA (MICs 3.2-5 g l-1; MBCs 10-15 g l-1), so the subsequent assays were carried out only with RPE and antimicrobials. RPE exerted a bacteriostatic action (MICs 0.0156-0.125 g l-1; MBCs 0.5-2 g l-1) but the combinations with IMI and ERTA showed the highest inhibition, as observed in the time-kill curve. However, the FICI index showed synergism (≥0.5) only to RPE + IMI. This combination was the most effective in inhibiting the biofilm and showed the highest values of membrane conductivity. Computational predictions indicated that RPE constituents may interact with PBP2a. CONCLUSION: RPE and RPE + IMI exerted an antibacterial and antibiofilm activity on MRSA strains probably due to membrane/wall damage and interactions with PBP2a.

Understanding antimicrobial susceptibility profile of Finegoldia magna: an insight to an untrodden path.

BACKGROUND: Finegoldia magna (formerly known as Peptococcus magnus or Peptostreptococcus magnus) belonging to phylum Firmicutes, class Clostridia and genus Finegoldia, is the only species known to cause infections in human beings. Amongst Gram positive anaerobic cocci, F. magna is known to be the most virulent with a high pathogenic potential. Significant upsurge in antimicrobial resistance among anaerobes has been documented by various studies. F. magna is known to be susceptible to most of the anti-anaerobic antimicrobials, however, multidrug resistant strains are being reported in literature. The present study was undertaken to highlight the role of F. magna in clinical infections and to analyze their antimicrobial susceptibility patterns. METHODS: The present study was conducted in a tertiary care teaching hospital in Southern India. 42 clinical isolates of F. magna recovered from diverse clinical infections between January 2011 to December 2015 were studied. These isolates were subjected to antimicrobial susceptibility testing against metronidazole, clindamycin, cefoxitin, penicillin, chloramphenicol and linezolid. RESULTS: Among the 42 isolates studied, majority of them were revived from diabetic foot infections (31%) followed by necrotizing fasciitis (19%) and deep-seated abscesses (19%). All the F. magna isolates showed good in-vitro activity against metronidazole, cefoxitin, linezolid and chloramphenicol. Clindamycin and penicillin resistance were observed against 9.5% and 2.4% of the isolates respectively. However, ß-lactamase activity was not detected. CONCLUSION: The antimicrobial resistance among anaerobes varies from pathogen to pathogen and region to region. Hence, a deep understanding of resistance pattern is necessary for better management of clinical infections.

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.

Pathogenic bacteria recovered from Gene X-pert tuberculosis-negative adult patients in Gondar, Northwest Ethiopia.

INTRODUCTION: Lower respiratory tract infections (LRTIs) caused by drug-resistant pathogenic bacteria is a major problem in developing countries including Ethiopia. Therefore, this study aimed to determine the pathogenic bacteria and their antimicrobial susceptibility patterns among Gene X-pert tuberculosis-negative adult patients with clinically suspected LRTIs at the University of Gondar Comprehensive Specialized Referral Hospital, Gondar, Northwest Ethiopia. METHODS: This institutional-based cross-sectional study was conducted from February 01 to March 15, 2020. Socio-demographic data were collected by using a structured questionnaire. A total of 254 sputum specimens were collected from Gene X-pert tuberculosis-negative patients. Bacterial recovery was performed using blood, chocolate, and MacConkey agar plates. Bacterial isolates were identified based on Gram staining, colony characteristics, and biochemical reactions. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Methicillin resistance of S. aureus was confirmed using cefoxitin (30 µg). Descriptive statistics were calculated for each variable and results are shown in tables and figures. RESULTS: In this study, the overall sputum culture positivity rate was 145/254 (57.1%). Gram-negative bacteria 111 (64.9%) were predominant compared to Gram-positive bacteria 60 (35.1%). Of the 145 culture-positive cases, 26 (14.8%) had poly-bacterial infections. S. aureus 40 (66.7%) was the predominant Gram-positive bacterium whereas K. pneumoniae 33 (29.7%), was the most isolated Gram-negative bacterium. Bacterial species, such as S. aureus were sensitive to ciprofloxacin 38/40 (95.0%), gentamicin 37/40 (92.5%), cefoxitin 36/40 (90.0%), and clindamycin 34/40 (85.0%). The proportion of Methicillin-resistant S. aureus was low, 4(10.0%). S. pneumoniae was sensitive to chloramphenicol 8/9 (88.9%) and resistant to ciprofloxacin 6/9 (66.7%). K pneumoniae, P. aeruginosa, E. coli, Serratia species, and H. influenzae also demonstrated high levels of resistance to ampicillin at rates of 21/33 (63.6%), 8/8 (100.0%), 15/17 (88.2%), 7/10 (70.0%), and 6/6 (100.0%), respectively. CONCLUSION: This study revealed a higher burden of Gram-negative and Gram-positive pathogenic bacterial agents, which is responsible for LRTs. Therefore, routine sputum culture identification and antibiotic susceptibility testing should be performed in Gene X-pert tuberculosis-negative patients.

Antibiotic Resistance Profiles and Molecular Characteristics of blaCMY-2-Carrying Salmonella enterica Serovar Albany Isolated from Chickens During 2013-2020 in South Korea.

The production of ß-lactamase by nontyphoidal Salmonella has become a public health issue throughout the world. In this study, we aimed to investigate the antimicrobial resistance profiles and molecular characteristics of ß-lactamase-producing Salmonella enterica serovar Albany isolates. A total of 434 Salmonella Albany were obtained from feces and carcasses of healthy and diseased food-producing animals [cattle (n = 2), pigs (n = 3), chickens (n = 391), and ducks (n = 38)] during 2013-2020. Among the 434 Salmonella Albany isolates, 3.7% showed resistance to cefoxitin, and all the cefoxitin-resistant isolates were obtained from chickens. Moreover, Salmonella Albany isolates demonstrated high resistance to nalidixic acid (99.3%), trimethoprim/sulfamethoxazole (97.9%), ampicillin (86.6%), chloramphenicol (86.6%), and tetracycline (85.7%), as well as higher rates of multidrug resistance were detected in cefoxitin-resistant isolates compared to cefoxitin-susceptible isolates. All cefoxitin-resistant isolates harbored CMY-2-type ß-lactamase and belonged to seven different pulsotypes, with type IV-b (43.75%) and IV-a (25%) making up the majority. In addition, genes encoding cefoxitin resistant of all blaCMY-2-harboring Salmonella Albany isolates were horizontally transmitted to a recipient Escherichia coli J53 by conjugation. Furthermore, 93.75% (15/16) of conjugative plasmids harboring blaCMY-2 genes belong to ST12/CC12-IncI1. Genetic characteristics of transmitted blaCMY-2 genes were associated with ISEcp1, which can play an essential role in the effective mobilization and expression of these genes. Salmonella Albany containing blaCMY-2 in chickens can potentially be transferred to humans. Therefore, it is necessary to restrict antibiotic use and conduct continuous monitoring and analysis of resistant bacteria in the poultry industry.

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.

[Evaluation of Antimicrobial Susceptibilities of Rapidly Growing Mycobacteria]. / Hizli Üreyen Mikobakterilerin Antimikrobiyal Ilaçlara Duyarliliklarinin Belirlenmesi.

Infections related to the rapidly growing mycobacteria (RGM), which are common in the environment, have clinical significance as they can affect both immunocompromised and immunocompetent patients. Treatment of RGM related infections is difficult, because they are resistant to many of the first-line tuberculosis agents, require a long-term multiple drug regimen, which is costly, and is associated with drugrelated toxicities. The aim of this study was to investigate the in vitro antimicrobial susceptibility profiles of RGM isolated in Dokuz Eylül University Hospital and also to reveal epidemiological data. A total of 58 isolates [(Mycobacterium fortuitum (n= 35), Mycobacterium abscessus (n= 19) and Mycobacterium chelonae (n= 4)], which were isolated in Dokuz Eylül University Hospital between 2013 and 2018, were subjected to in vitro testing for nine antimicrobial agents (amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem, linezolid, moxifloxacin and tobramycin) with the broth microdilution method recommended by the Clinical and Laboratory Standards Institute (CLSI). For M.abscessus; 73.68% of the isolates were found susceptible to amikacin; 73.68% of isolates were susceptible to clarithromycin at early reading and only 21.05% of them remained susceptible at late reading time. No resistance to imipenem were observed. M.abscessus isolates were highly resistant to tobramycin, doxycycline and fluoroquinolones. Antibiotic susceptibility testing of M.chelonae isolates demonstrated 100% susceptibility for amikacin, clarithromycin and tobramycin. No resistance to linezolid, imipenem and moxifloxacin were observed. None of the isolates were susceptible to cefoxitin. Ciprofloxacin and doxycycline also showed poor in vitro activity against M.chelonae isolates. For M.fortuitum clarithromycin susceptibility decreased from 32.35% to 2.94% after an additional incubation until 14 days. All tested isolates of the M.fortuitum were susceptible to amikacin, ciprofloxacin and moxifloxacin. None of the M.fortuitum isolates exhibited resistance to cefoxitin and imipenem. Most of the M.fortuitum isolates were resistant to tobramycin and doxycycline. When the results were evaluated together, RGM isolates in this study were highly susceptible to amikacin; and were highly resistant to doxycycline. In conclusion, this study supported that the status of antimicrobial susceptibilities were different between species and also showed the importance for hospitals to know susceptibility patterns of isolates in their region. It should be noted that accurate species determination is critical for treatment as well as susceptibility status of rapidly growing mycobacteria to the antimicrobials in use.

Extended Spectrum ß-Lactamase Activity and Cephalosporin Resistance in Escherichia coli from U.S. Mid-Atlantic Surface and Reclaimed Water.

Phylogenetic distribution and extended spectrum ß-lactamase (ESBL) activity of Escherichia coli recovered from surface and reclaimed water in the mid-Atlantic U.S. were evaluated. Among 488 isolates, phylogroups B1 and A were the most and least prevalent, respectively. Water type, but not season, affected phylogroup distribution. The likelihood of detecting group A isolates was higher in reclaimed than pond (P < 0.01), freshwater river (P < 0.01) or brackish river (P < 0.05) water. Homogeneity in group distribution was lowest in pond water, where group B1 comprised 50% of isolates. Only 16 (3.3%) isolates exhibited phenotypic resistance to one or more cephalosporins tested and only four had ESBL activity, representing groups B1, B2 isolates, and D. Phylogroup was a factor in antimicrobial resistance (P < 0.05), with group A (8.7%) and D (1.6%) exhibiting the highest and lowest rates. Resistance to cefoxitin was the most prevalent. Multi- versus single drug resistance was affected by phylogroup (P < 0.05) and more likely in groups D and B1 than A which carried resistance to cefoxitin only. The most detected ß-lactam resistance genes were blaCMY-2 and blaTEM. Water type was a factor for blaCTX-M gene detection (P < 0.05). Phenotypic resistance to cefotaxime, ceftriaxone, cefuroxime and ceftazidime, and genetic determinants for ESBL-mediated resistance were found predominantly in B2 and D isolates from rivers and reclaimed water. Overall, ESBL activity and cephalosporin resistance in reclaimed and surface water isolates were low. Integrating data on ESBL activity and ß-lactam resistance among E. coli populations can inform decisions on safety of irrigation water sources and One Health. IMPORTANCE Extended spectrum ß-lactamase (ESBL) producing bacteria, that are resistant to a broad range of antimicrobial agents, are spreading in the environment but data remain scarce. ESBL-producing Escherichia coli infections in the community are on the rise. This work was conducted to assess presence of ESBL-producing E. coli in water that could be used for irrigation of fresh produce. The study provides the most extensive evaluation of ESBL-producing E. coli in surface and reclaimed water in the mid-Atlantic United States. The prevalence of ESBL producers was low and phenotypic resistance to cephalosporins (types of ß-lactam antibiotics) was affected by season but not water type. Data on antimicrobial resistance among E. coli populations in water can inform decisions on safety of irrigation water sources and One Health.