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Objectives Haemophilus parainfluenzae is an opportunistic pathogen causing respiratory tract infection and sexually transmitted diseases. The emergence of multidrug resistance in this species is particularly worrisome, especially since the recent description of CTX-M-15 ESBL-producing isolates in Spain. The aim of this study was to characterize a CTX-M-15-producing H. parainfluenzae clinical isolate, HP01, obtained from a urethral swab. Methods MICs were determined with gradient strips for this isolate. Hydrolysis assays were performed with the β LACTA test. Genomic DNA from HP01 was subjected to Illumina and Oxford Nanopore sequencing to investigate the genetic environment of bla CTX-M-15. Phylogenetic analysis was performed with available H. parainfluenzae genomes from the NCBI database, including CTX-M-15 producers. Results HP01, an XDR isolate, was resistant to penicillin, third-generation cephalosporins, fluoroquinolones, macrolides, cyclines and co-trimoxazole and susceptible only to carbapenems and rifampicin. HP01 carried bla TEM-1, bla CTX-M-15, tet (M), catS and mef (E) /mel and harboured amino acid substitutions in PBP3, PBP5, GyrA, ParC and FolA implicated in resistance. Genomic analysis revealed that bla CTX-M-15 was carried by a Tn 3 -like transposon inserted into a novel integrative and conjugative element (ICE), ICE Hpa SLS, present on the chromosome and belonging to the ICE Hin1056 family described in Haemophilus influenzae. The tet (M)-MEGA element was also detected on the chromosome. No plasmid was found. The phylogenetic analysis showed that four H. parainfluenzae producing CTX-M-15 clustered in the same clade. Conclusions Here we report the description of an XDR H. parainfluenzae producing bla CTX-M-15 isolated from a urethral swab. The bla CTX-M-15 gene was inserted into an ICE structure similar to those recently described in CTX-M-15 producers in Spain. The emergence of XDR H. parainfluenzae producing bla CTX-M-15 is a matter of great concern. Careful surveillance is required to prevent its spread. [ABSTRACT FROM AUTHOR]

Background: Ventilator associated pneumonia (VAP) due to wild-type AmpC-producing Enterobacterales (wtAE) is frequent in intensive care unit (ICU) patients. Despite a low level of evidence, definitive antimicrobial therapy (AMT) with third generation cephalosporins (3GCs) or piperacillin is discouraged. Methods: Observational prospective study including consecutive wtAE VAP patients in 20 French ICUs. The primary objective was to assess the association of the choice of definitive AMT, i.e. piperacillin ± tazobactam (PTZ), 3GCs or other molecule (4GCs, carbapenems, quinolones, cotrimoxazole; control group), with treatment success at day-7. Recurrence of infection was collected as a secondary outcome, and analyzed accounting for the competing risk of death. Results: From February 2021 to June 2022, 274 patients were included. Enterobacter cloacae was the most prevalent specie (31%). Seventy-eight patients (28%) had PTZ as definitive AMT while 44 (16%) had 3GCs and 152 (56%) were classified in the control group. Day-7 success rate was similar between the 3 groups (74% vs. 73% vs. 68% respectively, p = 0.814). Recurrence probability at day-28 was 31% (95% CI 21–42), 40% (95% CI 26–55) and 21% (95% CI 15–28) for PTZ, 3GCs and control groups (p = 0.020). In multivariable analysis, choice of definitive AMT was not associated with clinical success, but definitive AMT with 3GCs was associated with recurrence at day-28 [csHR(95%CI) 10.9 (1.92–61.91)]. Conclusion: Choice of definitive antimicrobial therapy was not associated with treatment success at day 7. However, recurrence of pneumonia at day-28 was higher in patients treated with third generation cephalosporins with no differences in mortality or mechanical ventilation duration. [ABSTRACT FROM AUTHOR]

Copyright of Meandros Medical & Dental Journal is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Recent years, multi drug resistant pathogens and their pathogenicity were increased worldwide due to unauthorized consumption of antibiotics. In addition, correlation between multi drug resistant bacteria and biofilm formation is heightened due to the production of more virulence behavior. There is no better identification methods are available for detection of biofilm producing gram negative bacteria. Materials and methods: In this research work, multi drug resistant strains of Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) were identified based on the specific antibiotics and third generation cephalosporin discs by disc diffusion assay. Subsequently, biofilm forming ability of selected pathogens were identified tissue culture plate and tube test. Based on the multi-drug resistant ability and biofilm production, the molecular identification of P. aeruginosa and K. pneumoniae were confirmed by PCR using universal primers. Results and conclusions: No zone of inhibition present around the discs of muller hinton agar plates were confirm, selected P. aeruginosa and K. pneumoniae strains were multi drug resistant pathogens. Performed third generation cephalosporin antibiotics were also highly sensitive to selected pathogens of P. aeruginosa and K. pneumoniae. Further, biofilm forming ability of selected P. aeruginosa and K. pneumoniae was confirmed by tissue culture plate and tube methods. Finally, molecular identification of P. aeruginosa and K. pneumoniae was named as P. aeruginosa and K. pneumoniae. Our result was conclude, selected P. aeruginosa and K. pneumoniae as biofilm producing pathogens and also highly resistant to current antibiotics.

Background: Ceftriaxone and cefotaxime share a similar antibacterial spectrum and similar indications but have different pharmacokinetic characteristics. Ceftriaxone is administered once daily and 40% of its clearance is by biliary elimination, whereas cefotaxime requires three administrations per day and shows less than 10% biliary elimination. The high biliary elimination of ceftriaxone suggests a greater impact of this antibiotic on the gut microbiota than cefotaxime. The objective of this study was to compare the impact of ceftriaxone and cefotaxime on the gut microbiota. Methods: A prospective clinical trial was performed that included 55 patients treated with intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for at least 3 days. Three fresh stool samples were collected from each patient (days 0, 3, and 7 or at the end of intravenous treatment) to assess the emergence of third-generation cephalosporin (3GC)-resistant Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa, toxigenic Clostridioides difficile, and vancomycin-resistant enterococci. Results: The emergence of 3GC-resistant gram-negative enteric bacilli (Enterobacteriaceae) (5.9% vs 4.7%, p > 0.99), Enterococcus spp, and non-commensal microorganisms did not differ significantly between the groups. Both antibiotics reduced the counts of total gram-negative enteric bacilli and decreased the cultivable diversity of the microbiota, but the differences between the groups were not significant. Conclusion: No significant difference was observed between ceftriaxone and cefotaxime in terms of the emergence of resistance.

Recent years, multi drug resistant pathogens and their pathogenicity were increased worldwide due to unauthorized consumption of antibiotics. In addition, correlation between multi drug resistant bacteria and biofilm formation is heightened due to the production of more virulence behavior. There is no better identification methods are available for detection of biofilm producing gram negative bacteria. In this research work, multi drug resistant strains of Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) were identified based on the specific antibiotics and third generation cephalosporin discs by disc diffusion assay. Subsequently, biofilm forming ability of selected pathogens were identified tissue culture plate and tube test. Based on the multi-drug resistant ability and biofilm production, the molecular identification of P. aeruginosa and K. pneumoniae were confirmed by PCR using universal primers. No zone of inhibition present around the discs of muller hinton agar plates were confirm, selected P. aeruginosa and K. pneumoniae strains were multi drug resistant pathogens. Performed third generation cephalosporin antibiotics were also highly sensitive to selected pathogens of P. aeruginosa and K. pneumoniae. Further, biofilm forming ability of selected P. aeruginosa and K. pneumoniae was confirmed by tissue culture plate and tube methods. Finally, molecular identification of P. aeruginosa and K. pneumoniae was named as P. aeruginosa and K. pneumoniae. Our result was conclude, selected P. aeruginosa and K. pneumoniae as biofilm producing pathogens and also highly resistant to current antibiotics. [ABSTRACT FROM AUTHOR]

BackgroundThe prevalence of colonization with multidrug-resistant organisms (MDROs) among healthy adults in the community is largely unknown. This study investigated the colonization rate of multidrug-resistant Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in the community in Taiwan, and compared the gut microbiota between MDRO carriers and non-carriers.MethodsThis prospective cohort study was conducted from March 2017 to February 2018 at the Hsin-Chu and Jin-Shan branches of National Taiwan University Hospital. Nasal swabs and stool samples were obtained from healthy adults attending a health examination to screen for MDROs. Bacteria isolates of MDROs were tested for antibiotic susceptibility and resistant genes. Relevant data were collected using a standardized questionnaire to evaluate the risk factors for MDROs carriage, and 16S rRNA metagenomics sequencing was performed to analyze gut microbiota.ResultsAmong 187 participants, 4.6% (8/174) carried MRSA and 41.4% (77/186) carried third-generation cephalosporin-resistant (3GC-R) Escherichia coli or Klebsiella pneumoniae. The carriage rate of AmpC beta-lactamases and ESBL-producing strains were 16.1 and 27.4%, respectively. No carbapenem-resistant Enterobacteriaceae (CRE) or VRE were detected. The dominant resistant gene of E. coli isolates was CTX-M-type (73%), while that of K. pneumoniae was AmpC beta-lactamases (80%). In the multivariate analysis, the significant risk factors for carrying 3GC-R E. coli or K. pneumoniae were being an employee of technology company A [adjusted odds ratio (aOR) 4.127; 95% confidence interval (CI) 1.824–9.336; p = 0.001], and traveling to Southeast Asia in the past year (aOR 6.545; 95% CI 1.071–40.001; p = 0.042). The gut microbiota analysis showed that the phylum Proteobacteria and the family Enterobacteriaceae were significantly more abundant in 3GC-R E. coli and K. pneumoniae carriers.ConclusionA high rate of Taiwanese adults in the community carried 3GC-R Enterobacteriaceae, while no CRE or VRE colonization was noted. Compared with non-carriers, an expansion of Enterobacteriaceae in gut microbiota was found among 3GC-R Enterobacteriaceae carriers.

A large number of antibiotics are used for the treatment of uncomplicated cystitis owing to its high morbidity. As the administration of antibiotics for uncomplicated cystitis may be considered an example of inappropriate use, outpatient antimicrobial stewardship for this condition is important. We evaluated the current pharmacoepidemiology trends for the treatment of uncomplicated cystitis in Japan to predict stewardship strategies. This descriptive observational study analyzed data from an anonymized claims database of employees and their family members covered by the employer's health insurance. We identified female outpatients diagnosed with acute cystitis (ICD-10 code N300) aged ≥15 years and extracted oral antibiotic prescription records between 2013 and 2016. We excluded prescriptions for >7 days. The most prescribed antibiotic category was fluoroquinolones (52.67%), followed by cephalosporins and penems (40.63%). Third-generation cephalosporins accounted for 90.91% of cephalosporin and penem prescriptions. The most common duration of antibiotic prescription was 5 days, except for first-generation cephalosporins, penem (7 days) and sulfamethoxazole and trimethoprim (3 days). Fluoroquinolones and third-generation cephalosporins were prescribed to most uncomplicated cystitis cases in Japan. Although the lack of alternatives to quinolones and beta-lactams in Japan is an obstacle for antimicrobial stewardship for uncomplicated cystitis, promoting accurate diagnoses and establishing alternatives available in the Japanese market are important. Shortening the treatment duration is also an important strategy. Further research is needed on local antimicrobial resistance patterns to determine a fixed treatment strategy for uncomplicated cystitis. [ABSTRACT FROM AUTHOR]

Background: The prevalence of colonization with multidrug-resistant organisms (MDROs) among healthy adults in the community is largely unknown. This study investigated the colonization rate of multidrug-resistant Enterobacteriaceae , methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in the community in Taiwan, and compared the gut microbiota between MDRO carriers and non-carriers. Methods: This prospective cohort study was conducted from March 2017 to February 2018 at the Hsin-Chu and Jin-Shan branches of National Taiwan University Hospital. Nasal swabs and stool samples were obtained from healthy adults attending a health examination to screen for MDROs. Bacteria isolates of MDROs were tested for antibiotic susceptibility and resistant genes. Relevant data were collected using a standardized questionnaire to evaluate the risk factors for MDROs carriage, and 16S rRNA metagenomics sequencing was performed to analyze gut microbiota. Results: Among 187 participants, 4.6% (8/174) carried MRSA and 41.4% (77/186) carried third-generation cephalosporin-resistant (3GC-R) Escherichia coli or Klebsiella pneumoniae. The carriage rate of AmpC beta-lactamases and ESBL-producing strains were 16.1 and 27.4%, respectively. No carbapenem-resistant Enterobacteriaceae (CRE) or VRE were detected. The dominant resistant gene of E. coli isolates was CTX-M-type (73%), while that of K. pneumoniae was AmpC beta-lactamases (80%). In the multivariate analysis, the significant risk factors for carrying 3GC-R E. coli or K. pneumoniae were being an employee of technology company A [adjusted odds ratio (aOR) 4.127; 95% confidence interval (CI) 1.824–9.336; p = 0.001], and traveling to Southeast Asia in the past year (aOR 6.545; 95% CI 1.071–40.001; p = 0.042). The gut microbiota analysis showed that the phylum Proteobacteria and the family Enterobacteriaceae were significantly more abundant in 3GC-R E. coli and K. pneumoniae carriers. Conclusion: A high rate of Taiwanese adults in the community carried 3GC-R Enterobacteriaceae , while no CRE or VRE colonization was noted. Compared with non-carriers, an expansion of Enterobacteriaceae in gut microbiota was found among 3GC-R Enterobacteriaceae carriers. [ABSTRACT FROM AUTHOR]

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

Objectives: AmpC-β-lactamase production is an under-recognized antibiotic resistance mechanism that renders Gram-negative bacteria resistant to common β-lactam antibiotics, similar to the well-known ESBLs. For infection control purposes, it is important to be able to discriminate between plasmid-mediated AmpC (pAmpC) production and chromosomal-mediated AmpC (cAmpC) hyperproduction in Gram-negative bacteria as pAmpC requires isolation precautions to minimize the risk of horizontal gene transmission. Detecting pAmpC in Escherichia coli is challenging, as both pAmpC production and cAmpC hyperproduction may lead to third-generation cephalosporin resistance.Methods: We tested a collection of E. coli strains suspected to produce AmpC. Elaborate susceptibility testing for third-generation cephalosporins, WGS and machine learning were used to develop an algorithm to determine ampC genotypes in E. coli. WGS was applied to detect pampC genes, cAmpC hyperproducers and STs.Results: In total, 172 E. coli strains (n=75 ST) were divided into a training set and two validation sets. Ninety strains were pampC positive, the predominant gene being blaCMY-2 (86.7%), followed by blaDHA-1 (7.8%), and 59 strains were cAmpC hyperproducers. The algorithm used a cefotaxime MIC value above 6 mg/L to identify pampC-positive E. coli and an MIC value of 0.5 mg/L to discriminate between cAmpC-hyperproducing and non-cAmpC-hyperproducing E. coli strains. Accuracy was 0.88 (95% CI=0.79-0.94) on the training set, 0.79 (95% CI=0.64-0.89) on validation set 1 and 0.85 (95% CI=0.71-0.94) on validation set 2.Conclusions: This approach resulted in a pragmatic algorithm for differentiating ampC genotypes in E. coli based on phenotypic susceptibility testing. [ABSTRACT FROM AUTHOR]

Objectives: Clostridioides difficile infection (CDI) is one of the most important healthcare-associated infections. We aimed to describe the incidence density of healthcare-associated CDI (HA-CDI) in Germany's largest hospital and to identify associations with ward-level antimicrobial consumption.Methods: We used surveillance data on CDI and antimicrobial consumption from 2014 to 2017 and analysed a potential association by means of multivariable regression analysis.Results: We included 77 wards with 404998 admitted patients and 1850862 patient-days. Six hundred and seventy-one HA-CDI cases were identified, resulting in a pooled mean incidence density of 0.36/1000 patient-days (IQR = 0.34-0.39). HA-CDI incidence density on ICU and haematological-oncological wards was about three times higher than on surgical wards [incidence rate ratio (IRR) = 3.00 (95% CI = 1.96-4.60) and IRR = 2.78 (95% CI = 1.88-4.11), respectively]. Ward-level consumption of third-generation cephalosporins was the sole antimicrobial risk factor for HA-CDI. With each DDD/100 patient-days administered, a ward's HA-CDI incidence density increased by 2% [IRR = 1.02 (95% CI = 1.01-1.04)]. Other risk factors were contemporaneous community-associated CDI cases [IRR = 1.32 (95% CI = 1.07-1.63)] and CDI cases in the previous month [IRR = 1.27 (95% CI = 1.07-1.51)]. Furthermore, we found a significant decrease in HA-CDI in 2017 compared with 2014 [IRR = 0.68 (95% CI = 0.54-0.86)].Conclusions: We confirmed that ward-level antimicrobial use influences HA-CDI and specifically identified third-generation cephalosporin consumption as a risk factor. [ABSTRACT FROM AUTHOR]

Background: There is demonstrated benefit with fluoroquinolones as infection prophylaxis in neutropenic patients; however, side effects, drug interactions and increasing resistance necessitate investigation of alternative therapies.Objectives: To compare the incidence of febrile neutropenia in high-risk patients with haematological malignancy receiving a fluoroquinolone with those receiving an oral third-generation cephalosporin (OTGC) as antibacterial prophylaxis during chemotherapy-induced neutropenia.Methods: A retrospective, matched, single-centre study comparing clinical and microbiological outcomes in acute leukaemia patients receiving fluoroquinolones versus OTGCs as antibacterial prophylaxis after chemotherapy.Results: A total of 120 patients (levofloxacin n = 80, OTGC n = 40) were included and matched. The 30 day incidence of febrile neutropenia was 89.7% (95% CI = 82.4-93.9). The rates of febrile neutropenia were similar between antimicrobials (OTGC versus levofloxacin HR = 0.90, 95% CI = 0.54-1.52, P = 0.70). The most frequent site of infection was the bloodstream (line related) (n = 24, 62%) and the majority (n = 28, 72%) of infections were caused by Gram-positive organisms. Groups were similar in terms of site of infection (P = 0.91) and morphology of recovered microorganisms (P = 0.74). There were significantly more cultures positive for Enterobacter spp. in the OTGC group (P = 0.043). Three patients died during follow-up (from first dose up to 30 days after the last dose) (30 day survival = 99.2%, 95% CI = 97.5-100), with only two of the reported deaths attributable to infection.Conclusions: These findings demonstrate comparable rates of febrile neutropenia and culture positivity with an increase in cultures positive for Enterobacter spp. when OTGCs are compared with levofloxacin for antibacterial prophylaxis during chemotherapy-induced neutropenia. Further prospective, randomized investigation is warranted. [ABSTRACT FROM AUTHOR]

Infections due to extended spectrum β-lactamases (ESBL) producing Escherichia coli and Klebsiella pneumoniae have become an important clinical problem. Local knowledge of antimicrobial susceptibilities of these organisms is important for implementation of effective hospital anti-infective policies. The present study was undertaken to determine the prevalence of ESBLs along with their antimicrobial sensitivity pattern in Escherichia coli and klebsiella pneumoniae isolates at a tertiary care hospital in Bangalore. A total of 243 clinical isolates comprising E. coli (n=157) and K. pneumoniae (n=86) were recovered from various clinical samples over a period of six months from June to November 2008. Antibiogram profile of these isolates was determined by Kirby-Bauer’s disc diffusion method. All the isolates were screened for ESBL production as recommended by the Clinical Laboratory Standard Institute (CLSI). The present findings revealed a high occurrence of multidrug resistance ESBL producing E. coli (61.1%) and K. pneumoniae (40.6%). Imipenem was highly active against ESBL producing isolates. Results indicate that routine ESBL detection should be made imperative and empirical use of third generation cephaolsporins must be discouraged.

Background: The aim of this study was to determine the serotypes and antimicrobial susceptibility of Shigella spp. in Isfahan, (Iran) from 2010 to 2015. Methods: This retrospective study was conducted on Shigella isolates in four tertiary care hospitals. The process of bacterial isolation and determination of susceptibility was performed by standard microbiological guidelines. The patients were categorized into three age groups of under 5, 5-15 and over 15 years. Results: Among 45 isolates, S. sonnei (63.6%) was the predominant species, followed by S. flexneri (34.1%), and S. dysenteriae (2.3%). Substantial resistance to ampicillin, trimethoprim- sulfamethoxazole, ceftriaxone, cefotaxime, and cefixime was observed. Over 94% of the isolates were sensitive to ciprofloxacin. Susceptibility of isolates was similar between all age groups. Conclusion: Significant resistance to third generation cephalosporins precludes the use of these agents for empirical treatment of shigellosis in our population. Ciprofloxacin is an appropriate option; however, susceptibility tests should be performed before prescription. [ABSTRACT FROM AUTHOR]

The sensitivity of NG-test CTX-M Multi assay and BL-RED test incubated 10 min for the detection of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae was 80.6% and 90.3% respectively. Using an extended 60 min incubation with the BL-RED test, its sensitivity was increased to 100% and 60.9% for ESBL-producing and cephalosporinase-overexpressing Enterobacteriaceae respectively. [Display omitted] • Determination of 3GC resistance requires rapid phenotypic screening tests • BL-RED is an electrochemical test allowing detection of 3GC resistance • BL-RED sensitivity was found superior to that of NG-test CTX-M Multi for detection of ESBL • Extended incubation to 1 h detected 2/3 strains with overexpressed cephalosporinase • BL-RED is a good tool for rapid detection of 3GC resistance in Enterobacteriaceae [ABSTRACT FROM AUTHOR]

Choice of antibiotic for treatment of serious bacterial infection is rapidly diminishing by plasmid mediated transfer of antibiotic resistance. Here, we report a possible horizontal transfer of plasmid carrying third-generation-cephalosporin (TGC) resistance between Escherichia coli and Shigella sonnei . Two different types of colonies were identified in MacConkey agar plate from a faecal specimen collected from a patient with shigellosis. The colonies were identified as E. coli and S. sonnei . Both of the isolates were resistant to ampicillin, chloramphenicol, co-trimoxazole, erythromycin, azithromycin, nalidixic acid, ceftriaxone, cefixime, ceftazidime, cefotaxime and susceptible to co-amoxiclave, amikacin, imipenam, astreonam, levofloxacin, moxifloxacin, mecillinam. These two strains were positive for extended spectrum β -lactamase. We were able to transfer ESBL producing property from both ceftriaxone-resistant isolates to the ceftriaxone susceptible recipient E. coli K12 and S. sonnei . Plasmid profile analysis revealed that the first-generation E. coli K12 and S. sonnei transconjugants harbored a 50 MDa R plasmid, as two-parent ESBL-producing S. sonnei and E. coli strains. Similar patterns of ESBL producing plasmid and transferable antimicrobial phenotype suggests that the ESBL producing plasmid might transferred between E. coli and S. sonnei through conjugation in the human gut. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Taibah University Medical Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The incidence of sepsis and death caused by sepsis increases each year. Beta-lactam antibiotics is widely used to treat many types of infections because of its minimum side-effects. As a result of the widespread use of broad spectrum cephalosporin, an Extended Spectrum β-lactamase (ESBL) enzyme produced by K. ozaenae has developed. Since then, other types of ESBL have been found and spread around the world relatively fast. The prevalence of infection caused by ESBL-producing bacteria varies in each country. In Indonesia, the incidence of ESBL in Enterobacteriaceae is still not widely known. This research aims to investigate the prevalence of ESBL in third generation cephalosporin usage among sepsis patients in The Department of Internal Medicine of RSUD Dr. Soetomo Surabaya. This crossectional study is conducted in The Department of Internal Medicine RSUD Dr. Soetomo Surabaya between November 1st 2011 and February 29th 2012. Demographic characteristics of patients and the basic diagnose were obtained from the medical record. Specimen were collected to examine bacterial culture and antibiotic sensitivity testing, complete blood laboratory examination, complete urine examinationm liver function tests and kidney function test. Data were analyzed using SPSS 18.0. Of the 30 sepsis patients, 2 were ESBL-positive (6.66%). ESBL-positive incidence were in the age group 41-50 and 61-70 years old, all male. Pneumonia and hepatobilliary disease were the underlying disease. ESBL-positive culture were obtained in blood and sputum isolates. ESBL-producing bacteria were Klebsiella pneumoniae dan Enterobacter coxacie with the most sensitivity towards levofloxacin, imipenem and meropenem. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This study had for objective to assess the frequency of resistance to fluoroquinolones and to third generation cephalosporin in E. coli isolated from urines of consulting and hospitalized patients and to detect the rate of multiresistant E. coli strains. Design: A retrospective survey was made over 3 years (1st January 2005 to 31st December 2007). Eight hundred and nineteen patients presented with UTI confirmed in the Rabat Cheikh Zayd Teaching Hospital. Results: E. coli was the etiologic agent in 57% of reported UTI. The frequency of E. coli resistance to fluoroquinolones was 27% with a higher rate among hospitalized patients. We found that ten E. coli strains were producing extended-spectrum β-lactamase and resistant to aminosides and fluoroquinolones. Conclusions: The resistance of E. coli to fluoroquinolones is becoming worrying among consulting and hospitalized patients. Ten strains multiresistant to fluoroquinolones and third generation cephalosporins, probably because of plasmids, were isolated. This increasingly frequent resistance mechanism should lead to a more careful use of first line fluoroquinolones for UTI. [Copyright &y& Elsevier]

The aim of this study was to assess colonisation and transmission of third-generation cephalosporin-resistant Enterobacteriaceae (CRE) from patients in 16 intensive care units. A prospective, repetitive point prevalence survey was performed over 6 months, involving samples from 1851 patients. CRE were isolated from 186 (10%) patients, with Enterobacter spp. being the most common. Mean point prevalence rates were significantly higher for paediatric wards (22.5%) compared to surgical (8.1%) and medical (5.5%) units. All CRE isolates were typed by pulsed-field gel electrophoresis. Non-outbreak nosocomial transmission rates of these pathogens were calculated as 12.8% for paediatric patients, compared to 6.8% for adult patients, which may reflect differences in sensitivity to overgrowth with resistant bacteria and contact with health care workers. [ABSTRACT FROM AUTHOR]

A high-performance liquid chromatography isocratic procedure was developed for the assay of cefetamet pivoxil hydrochloride in drug substance and powder for oral suspension. The method validation yielded good results and included the range, linearity, precision intra- inter-day, accuracy, specificity, LOD and LOQ values. The chromatographic system consisted of a C18 absorbosphere column (150×4.6 mm i.d., 5 μm particle size), a mobile phase composed of water–acetonitrile–methanol–phosphate buffer, pH 3.5 (50:35:10:5, v/v), flow rate of 1.5 ml min−1 and UV detection at 254 nm. The relative standard deviation varied between 0.03 and 1.76%, and accuracy of 100.09% was found. Calibration curve was linear from 30.0–80.0 μg ml−1; its correlation coefficient was 0.99989. [Copyright &y& Elsevier]

Background: Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and have become more difficult to treat over the years. Inappropriate antibiotic use has led to increased antibiotic resistance., Materials and Methods: We examined 1921 urine culture samples from a single hospital and analyzed them for bacterial spectrum and antibiotic susceptibility. We further analyzed changes in the rates of detected bacteria and of the sensitivity of these uropathogens to antibiotics over the years., Results: In our hospital-based analysis, cystitis was the most frequently diagnosed UTI in women (76%) and men (79%). Escherichia coli (48%) was the most commonly identified uropathogen. Samples demonstrated an increase in the proportion of E. coli (p   <  0.001) and a decrease in Enterococcus faecalis (p   <  0.001) over the study time period. Antimicrobial susceptibility analysis showed an increase over time in the number of isolates with resistance to ampicillin/sulbactam (p   <  0.001) and to third-generation cephalosporins cefotaxime (p   =  0.043) and ceftazidime (p   <  0.001)., Conclusions: Ampicillin/sulbactam and third-generation cephalosporins are antibiotics frequently used in the treatment of UTIs. When selecting an optimal antimicrobial treatment regimen for patients with UTIs, it is imperative to understand regional and timedependent differences in the prevalence of various uropathogens and antimicrobial resistance patterns. Therefore, continuous surveillance of local pathogen and antimicrobial susceptibility patterns for frequently used antibiotics should be prioritized., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Background Despite increased public health awareness of ESBLs and CRE, limited data exist regarding the true frequency of these resistant bacteria in urine cultures collected from adult patients in US hospitals. This study sought to quantify the prevalence and rates of ESBLs and CRE from urine cultures in adult hospitalized patients with ENT. Methods All hospitalized adults with a urine culture (first urine isolate of a species per 30-day period) from 377 hospitals in 2018 were evaluated (BD Insights Research Database, Becton, Dickinson & Company). ESBL was defined as an ENT that was ESBL-positive per commercial panels or intermediate or resistant (non-susceptible, [NS]) to a third-generation cephalosporin; CRE was defined as an ENT that was NS to imipenem, meropenem, doripenem or ertapenem. Urine isolates were classified as community-onset (CO: < 3 days of an inpatient admission and no previous admission within 14 days) or hospital-onset (HO: ≥ 3 days post-admission or within 14 days of discharge) period. Prevalence and rates per 100 admissions were calculated overall, by onset location (CO vs. HO), and by US Department of Health and Human Services (HHS) geographic region. Results In 2018, there were 193,476 non-duplicate ENT urine isolates across 4,623,333 admissions; 63.6% were E. coli (EC), 19.5% were K. pneumoniae / oxytoca (KPO), and 8.7% were P. mirabilis (PM). Overall, 12.6% were ESBL and 0.9% were CRE. Rate per 100 admissions was 0.484 and 0.037 for ESBL and CRE, respectively. Among CO, 11.8% were ESBLs and ESBL rates per 100 admissions were 0.358; 0.7% were CRE and CRE rates per 100 admissions was 0.024. Among HO, 15.7% were ESBLs and ESBL rates per 100 admissions was 0.126; 1.5% were CRE and CRE rates per 100 admissions was 0.013. Regional differences in both ESBL and CRE ENT were noted (table). Conclusion The prevalence of ESBLs/CRE among adult hospitalized patients with ENT in a urine culture was 13% and 1%, respectively. The % ESBL/CRE was higher among patients HO urine isolates whereas ESBL/CRE rates per 100 admissions were higher among patients with CO urine isolates. Considerable geographic variations were observed. Region and site of onset differences in ESBL/CRE epidemiology should be considered when making empiric antibiotic treatment decisions. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background There are advantages and challenges associated with enteric multiplex PCR testing. Fast turnaround time can lead to prompt pathogen identification and antibiotic initiation, decreased length of stay and decreased time in isolation. Challenges include identification of multiple organisms, carrier state detection, and detection of organisms with uncertain pathogenic potential, which can lead to unnecessary antibiotic use. Methods Two institutions transitioned from stool culture to stool PCR testing for identification of diarrheal pathogens. On February 1, 2016, Center 1 employed the BioFire® FilmArray® GI Panel, which detects 22 organisms and includes targets of unclear clinical significance. Center 2 implemented the BD MAX™ Enteric Bacterial Panel on 3/6/2019, which reports 4 bacterial known pathogens. Fluoroquinolone (FQ) and third-generation cephalosporin (TGC) prescribing in response to positive PCR testing was assessed over a 1 month period. Antibiotics were counted when prescribed within 72 hours of the collection date. Results At Center 1, 332 GI PCR panels were ordered, 94 (28.3%) were positive and 15 (16%) were treated; 4 received an FQ (26%), and 11 (73%) received a TGC. Center 1 organisms included 44 Clostridioides difficile , 27 Norovirus, 8 Enteropathogenic E. coli , 7 Sapovirus, 4 Campylobacter species, 2 Giardia lamblia, 2 Rotavirus, 1 Shigella /Enteroinvasive E. coli and 1 Salmonella species. Of 642 PCR tests ordered at Center 2, 16 (2.5%) were positive and 11 (69%) were treated; 10 (91%) received a FQ, and 1 (9%) received a TGC. Center 2 organisms included 8 non-typhoidal Salmonella species, 5 Aeromonas species, 2 Shigella sonnei and 1 Salmonella typhi. Conclusion Implementation of an enteric multiplex PCR test with targets of uncertain clinical significance is more likely to yield an abnormal result than a PCR test with only known pathogens. However, careful interpretation of results can avoid unnecessary antimicrobial use. Antimicrobial stewardship teams should work in tandem with microbiology laboratories to implement enteric multiplex PCR tests and monitor the impact on antibiotic use. Larger studies are needed to definitively assess the impact of the GI panel on antimicrobial prescribing within the context of patient comorbidities and institutional practices. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The US CDC has identified a number of antibiotic-resistant (AR) bacteria as urgent or serious public health threats. This study sought to quantify the prevalence and incidence of extended-spectrum β-lactamase (ESBL) Enterobacteriaceae (ENT), Carbapenem-resistant ENT (CRE), P. aeruginosa (Carb NS-PsA), vancomycin-resistant enterococci (VRE), and methicillin-resistant S. aureus (MRSA) in the urine of adult hospitalized patients. Methods All hospitalized adult patients with a positive urine culture (first urine isolate of a species per 30-day period) were evaluated from over 400 US hospitals (2013–2018; BD Insights Research Database, Becton, Dickinson and Company). The following five groups of AR bacteria were examined: (1) ESBL ENT if ESBL-positive per commercial panels or intermediate/resistant (non-susceptible [NS]) to a third-generation cephalosporin; (2) CRE ENT if NS to imipenem (IPM), meropenem (MEM), doripenem (DOR) or ertapenem; (3) Carb-NS PsA if NS to IPM, MEM or DOR; (4) VRE if resistant to vancomycin; and (5) MRSA as resistant to methicillin/oxacillin. For each AR grouping, % NS and rates of NS per 100 admissions were calculated and trends were examined using Logistic regression and Poisson models. Results Across the 6-year study period, there were 24,558,856 admissions, accounting for 2,285,971 non-duplicate urine isolates; 1,016,642 were ENT, 87,450 were PSA, 203,231 were enterococci, and 41,979 were S. aureus. The % of NS for ESBL, CRE ENT, Carb-NS PsA, VRE, and MRSA were 12%, 0.9%, 13%, 19%, and 55%, respectively. The % of NS for ESBL increased from 2013 to 2018 (P < 0.001) whereas % NS for PsA and % MRSA decreased during the same time period (P < 0.001) (Figure 1). The rates of NS per 100 admissions for ESBL, CRE ENT, Carb-NS PsA, VRE, and MRSA were 0.44, 0.04, 0.05, 0.16, and 0.09, respectively. The annual NS rates per 100 admission trends for ESBL and CRE ENT were increasing (all P < 0.0001) while the trends for Carb-NS PsA, VRE, and MRSA were decreasing (all P < 0.0001). Conclusion While the percent of ESBL, CRE ENT, Carb-NS PsA, VRE, and MRSA have remained relatively constant over the past 6 years, there has been a notable increase in the rates of ESBL and CRE ENT per 100 admissions among adult hospitalized patients with positive urine cultures. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae has been classified as critical priority pathogens. The novel extended-spectrum β-lactamase (ESBL) inhibitor enmetazobactam (formerly AAI101; EMT) in combination with cefepime (FEP) is currently being developed as a carbapenem-sparing treatment of serious Gram-negative infections in settings with a high prevalence of 3GC-resistant Enterobacteriaceae. We report here the results from a phase 2 study that assessed safety, tolerability, and pharmacokinetics of FEP-EMT in patients with cUTI/AP. Methods Forty-five patients were enrolled in a randomized, multicenter, double-blind study of hospitalized adults with cUTI/AP. Patients received dosing regimens of FEP or FEP-EMT IV therapy q8h by 2 hours infusion (table) for 7 to 10 days with a 28-day follow-up. Efficacy was evaluated in the microbiological-modified ITT (µMITT) population. Safety was monitored in patients who received at least 1 dose of study drug. Clinical cure was designated as the resolution of cUTI symptoms present at study entry. Plasma and urine PK were determined from all patients. Results The study drugs were well tolerated in each cohort, with similar % adverse events and no new or unexpected safety concerns (table). Two discontinuations were due to allergic dermatitis. The microbiological- and clinical responses at test-of-cure for the combined FEP-EMT group were 83.3% (20/24) and 95.8% (23/24) compared with responses in the combined FEP group of 73.3% (11/15) and 93.3% (14/15), respectively (table). The most common baseline pathogens were Escherichia coli (66.7%) and Klebsiella pneumoniae (23.1%): 28.2% of isolates produced ESBLs with eradication rates for the combined FEP-EMT group of 85.7% (6/7) and for the combined FEP group of 75.0% (3/4). FEP and EMT PK were best described by a 2-compartment, linear PK model. Both agents exhibited half-lives of 2.3 hours. Creatinine clearance had a significant covariate effect on FEP and EMT, consistent with predominant renal excretion of both agents. Conclusion Results from this phase 2 study justify advancement to phase 3 studies to evaluate the safety and efficacy of FEP-EMT in patients with cUTI/AP. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background In response to increasing rates of antimicrobial resistance, carbapenems have become first-line treatments for many infections. This, in turn, fosters the potential for resistance (CR). Efforts to mitigate the emergence of CR through carbapenem-sparing strategies must rest on a fundamental understanding of antibiotic resistance patterns among commonly encountered pathogens. Therefore, we examined the microbiology of complicated urinary tract infections (cUTI) in hospitalized patients in the United States. Methods We performed a multicenter retrospective cohort study in the Premier database of approximately 180 hospitals, 2013–2018. Using an ICD-9/10-based algorithm we identified all adult patients hospitalized with cUTI and included those with a positive blood or urine culture. Patients with carbapenem-resistant organisms were excluded. We examined the microbiology and susceptibilities to common cUTI antimicrobials (third-generation cephalosporin [C3], fluoroquinolones [FQ], trimethoprim-sulfamethoxazole [TMP/SMZ], fosfomycin [FFM], nitrofurantoin [NFT], and triple-resistant [TR]) over time. Results Among 28,057 organisms from 23,331 patients, the 3 most common pathogens were E. coli (EC, 41.0%), K. pneumoniae (KP, 12.1%), and P. aeruginosa (PA, 11.0%). Among these organisms, resistance to C3 was 10.4% among PA, 12.6% KP and 48.9% EC. EC was most likely to exhibit resistance to all agents of interest, and demonstrated the highest resistance rate to TMP/SMZ (61.5%), and lowest to NFT (10.4%). In contrast, KP had the highest rate of resistance to NFT (27.9%) and lowest to FQ (4.9%). The lowest rate of resistance among PA was to TMP/SMZ (1.9%), and highest to C3 (10.4%). The prevalence of TR in 2013–2014 and 2017–2018, respectively, was 34.2% and 37.4% for EC, 11.8% and 14.2% for KP, and 7.0% and 4.6% for PA. Conclusion Among the most common pathogens isolated in hospitalized patients with cUTI, and particularly in EC, high and increasing single resistance and TR rates to common antimicrobials were evident, Current empiric treatment strategies may be insufficient against the growing threat of TR. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Complicated urinary tract infection (cUTI) is common among hospitalized patients. Though carbapenems are an effective treatment in the face of rising resistance, overuse drives carbapenem resistance (CR). We hypothesized that resistance to routinely used antimicrobials is common, and, despite the frequent use of carbapenems, associated with an increased risk of inappropriate empiric treatment (IET), which in turn worsens clinical outcomes. Methods We performed a multicenter retrospective cohort study in ~180 hospitals in the Premier database, 2013–2018. Using an ICD-9/10-based algorithm we identified all adult patients hospitalized with cUTI and a positive blood or urine culture (CR excluded). We examined with the impact of triple resistance (TR; resistance to > 3 of the following drugs/classes: third-generation cephalosporin [C3R], fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin), on the risk of receiving IET. We derived multivariate models to compute the impact of IET on hospital outcomes. Results Among 23,331 patients with cUTI (96.2% community-onset), 3,040 (13.0%) had a TR pathogen. Compared with those with non-TR, patients with TR were more likely male (57.6% vs. 47.7%), black (17.9% vs. 13.6%), and in the South (46.3% vs. 41.5%), P < 0.001 each; had a higher median Charlson score (3 vs. 2), and were more likely to need early ICU (22.3% vs. 18.6%) and mechanical ventilation (7.0% vs. 5.0%), P < 0.001 each. Patients with TR were hospitalized at centers with higher median prevalence of both C3R (16.3% vs. 14.4%) and TR (15.1% vs. 12.2%), P < 0.001 each. IET was more frequent in TR than non-TR group (19.6% vs. 5.4%) despite greater empiric carbapenem use in TP (43.3% vs. 16.2%), P < 0.001 each. Though IET did not have an impact on adjusted hospital mortality or 30-day readmission rate, it was associated with excess adjusted resource utilization ($1,364 in costs and 0.66 day in length of stay). Conclusion Among hospitalized patients with cUTI, TR is common, and is associated with a nearly 4-fold increase in exposure to IET, which in turn contributes to excess resource utilization. Given the high prevalence of TR, clinicians should consider a lower threshold for broader empiric treatment in appropriate patients. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to examine the change in clinical characteristics of community-acquired acute pyelonephritis (CA-APN) in South Korea between 2010–2011 and 2017–2018. Methods We recruited all CA-APN patients with age ≥19 years who visited 4 hospitals in South Korea from September 2017 to August 2018, prospectively. The inclusion criteria were: (i) presence of fever (body temperature ≥37.8°C), (ii) pyuria [≥5–9 white blood cells per high power field (WBC/HPF)], and (iii) clinical symptoms or signs relevant to APN. Patients diagnosed with APN more than 48 hours after admission, those transferred from other hospitals during treatment of APN, those with other reasons for fever and pyuria, and those with insufficient data were excluded. Each patient was included for the first episode during the study period. The collected data were compared with those from the previous study with the same design in 2010–2012, in which the same hospitals were participated. Results A total of 349 and 472 patients were recruited during 2017–2018 and 2010–2011, respectively. E. coli was the most common causative pathogen for CA-APN in both periods (87.5% vs. 86.6%, P = 0.727). Significantly higher antimicrobial resistance against fluoroquinolone (33.5% vs. 21.0%, P = 0.001), cefotaxime (34.8% vs. 7.6%, P P = 0.040) were observed for E. coli isolates in 2017–2018 compared with those in 2010–2011. The patients in 2017–2018 were older (60.71±17.29 vs. 55.77±18.60, P < 0.001) and had higher Charlson's comorbidity index (1.04±1.39 vs. 0.68±1.17, P <0.001) than those in 2010–2011. Total duration of antibiotic treatment increased from 15.40 ± 6.35 days in 2010–2011 to 21.74 ± 11.72 days in 2017–2018, P < 0.001); the proportion of patients using carbapenem increased from 6.1% in 2010–2011 to 26.6% in 2010–2011 (P < 0.001). The median days of admission was higher for patients in 2017–2018 than those in 2010–2011 (10 vs. 8, P < 0.001). Conclusion Patients with CA-APN in South Korea were aging. Antimicrobial resistance of E. coli to almost all antibiotic classes, especially third-generation cephalosporin, increased significantly and total duration of antibiotic treatment and proportion of carbapenem usage increased, consequently. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Ceftazidime/avibactam (CZA) is a combination of a third-generation cephalosporin and a diazabicyclooctane β-lactamase inhibitor, which is active against a broad range of class A, C and D β-lactamases. In Colombia, high rates of multidrug-resistant Enterobacteriaceae (Ent)and P. aeruginosa (Pae) have been reported. Of special concern are KPC enzymes endemic in Ent and found in Pae, which are associated with higher mortality and healthcare costs, as well as limited therapeutic options. Herein, we evaluate the susceptibility of clinical isolates of carbapenem nonsusceptible Ent (CNS-E) and Pae (CNS-P) to CZA with the aim of understanding its role as a therapeutic option for these bacteria. Methods Three hundred ninety-nine nonduplicate clinical isolates of carbapenem nonsusceptible Gram-negative bacilli were collected in 13 medical centers from 12 Colombian cities, from January 2016 to October 2017 (137 K. pneumoniae [ Kpn ], 76 E. coli , 34 Enterobacter spp. 21 S. marcescens [ Sma ] and 131 Pae). CNS-E was defined as minimum inhibitory concentrations (MIC) ≥1 mg/L for ertapenem and CNS-P was defined as MIC ≥4 mg/L for meropenem. MIC were determined by broth microdilution and interpreted according to current CLSI guidelines. CZA MIC were determined using double dilutions of ceftazidime and a fixed concentration of avibactam of 4 mg/L. Comparator agents were ceftazidime, cefepime, piperacillin/tazobactam, imipenem, meropenem, tigecycline (TGC), and fosfomycin (FOS). Results Antimicrobial activity of CZA and comparators is shown in Table 1. CZA susceptibility ranged from 69% in Kpn to 81% in Sma, whereas 49% of CNS-P were susceptible to CZA. In both, CNS-E and CNS-P, CZA was superior to all other tested β-lactam compounds. Notably, in CNS-E CZA susceptibility was comparable to FOS and TGC (except for TGC in Sma). Conclusion CZA is the most active β-lactam against CNS-E and CNS-P. CZA nonsusceptibility suggests the presence of other resistance mechanisms, such as class B β-lactamases that are not inhibited by avibactam, and which are more frequently reported in CNS-P. Our results highlight the key role of new agents such as CZA in KPC endemic countries and the need for surveillance studies to determine the nature of resistance mechanisms. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background β-Lactam antibiotics, specifically nafcillin, oxacillin, and cefazolin, have proven efficacy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Outpatient antimicrobial therapy (OPAT) with these agents is limited due to side effects and multiple doses required per day. Ceftriaxone, a third-generation cephalosporin, has a favorable profile for OPAT. Limited evidence supporting ceftriaxone therapy for MSSA infections prevents its widespread use. Methods A multi-center, retrospective cohort study comparing patients who received cefazolin or nafcillin to patients who received ceftriaxone for treatment of microbiologically proven MSSA infections was conducted from February 2016 to February 2018. The primary outcome of interest was a clinical success, defined as the absence of infection-related readmission, worsening infection, or recurrent infection within 90 days. Secondary outcomes included the rate of adverse reactions, length of stay, and impact of Infectious Diseases (ID) consult. Results 66 patients treated with ceftriaxone and 156 patients treated with cefazolin or nafcillin were included. Skin and soft tissue and bone and joint were the most common infections in the ceftriaxone group, whereas bacteremia was most common in the nafcillin and cefazolin group. There were significant differences in baseline age (61 years vs. 59 years; P = 0.036) and intravenous drug use (1 patient vs. 25 patients; P = 0.002) between groups. As shown in Table 1, there were significantly lower rates of clinical success with ceftriaxone compared with standard of care as a composite of all infection sites (78.8% vs. 91%; P = 0.012). No statistically significant differences were seen in safety outcomes or ID consultation. Length of stay was significantly longer in the nafcillin and cefazolin group (5.2 days vs. 12.8 days; P ≤ 0.0001). Conclusion The results of this study indicate that patients treated with ceftriaxone for MSSA infections had significantly lower rates of clinical success compared with standard of care antibiotics. Nafcillin or cefazolin should remain as first-line agents for treatment of bone and joint infections and skin and soft-tissue infections due to MSSA. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background There is growing interest about the deleterious impact of antibiotics on loss of gut symbiosis, called dysbiosis. As patients with BJI require antibiotics usually during 6 to 12 weeks, it is of interest to determine whether dysbiosis is frequent in this population, and if it could potentially reversible or not. Methods Multicentric prospective cohort study in France (EudraCT 2016-003247-10) including patients with 3 categories of BJI: native, osteosynthesis-related and prosthetic joint infection (PJI). At the time of suspicion (V1), at the end of therapy (V2) and then 2 weeks after stopping therapy (V3), blood and fecal samples were collected. Extracted DNA from stool was sequenced using shotgun metagenomic sequencing based on illumina library and Iseq instrumentation. Data run through a dedicated pipeline in order to produce microbiome indexes such as Sympson or Shannon diversities indexes. Gut microbiome and inflammation markers were analyzed including fecal neopterin, a maker of gut inflammation. Results Concerning the 62 patients included (mean age, 60 years; mean duration of antibiotics, 66 days), 27 had native, 14 had osteosynthesis and 21 had PJI. The most frequently prescribed drug was a fluoroquinolone, followed by a third-generation cephalosporin and vancomycin. Stools from 42 of them were analyzed as per protocol. Overall, the mean Shannon richness index decreased from 0.904 at V1 to 0.845 at V2; the Bray-Curtis index underlined the difference in microbiome reconstitution at V3 in comparison with V1. We report significant microbiome loss of diversity at V2, that was reversible at V3 in patients with native BJI and osteosynthesis-related BJI, but not in patients with PJI (figure). Fecal neopterin increased between V1 and V2 (mean 221.6 and 698.1 pmol/g of feces, respectively) and then decreased at V3 (422.5 pmol/g), and could be a potential surrogate marker of gut dysbiosis. Of note, patients with abnormal CRP at the end of antibiotics had high neopterin values, that raises the hypothesis that abnormal CRP at the end of antibiotics could be in relation with gut dysbiosis rather than uncured BJI. Conclusion The impact of antibiotics on the gut microbiota of patients with BJI seems to be significant, especially in patients with PJI who could be candidate for fecal microbiota transplantation. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Complicated intra-abdominal infections (cIAI) remain an important cause for hospitalization. Evidence-based guidelines recommend reserving broad-spectrum antibiotic coverage for high-risk cases in order to reduce overuse of certain antibiotic classes, particularly in the face of emerging carbapanem resistance. We examined the factors associated with use of empiric carbapenem treatment (ECT) among hospitalized patients with cIAI. Methods We performed a multicenter retrospective cohort study in the Premier database of approximately 180 hospitals, 2013–2017. Using an ICD-9/10 based algorithm including a requirement for a laparotomy/laparoscopy, we identified all adult patients hospitalized with cIAI and included those with a positive blood or abdominal culture. We derived and tested a multivariable logistic regression model to examine predictors of ECT. Results Among 321,317 hospitalized patients with cIAI, 4,453 (1.4%) were culture-positive, 1,185 (26.6%) of whom received ECT. Among those given ECT, >50% (682) had no risk factors for resistance, and in only 120 (10.1%) was an organism resistant to a third-generation cephalosporin (C3R extended spectrum β-lactamase [ESBL] phenotype) isolated. The top 5 variables associated with ECT use were: pre-cIAI anti-fungal therapy (OR 2.57, 95% CI 1.91, 3.45) urgent (vs. emergent) admission (OR 1.56, 95% CI 1.21, 2.01), corticosteroids (OR 1.50, 95% CI 1.13, 1.99), ICU admission (OR 1.46, 95% CI 1.17, 1.82), and presence of sepsis/septic shock (OR 1.43, 95% CI 1.18, 1.74). The model had a moderately good fit (c-statistic = 0.683; 95% CI (0.665, 0.700), Hosmer-Lemeshow P value = 0.411). Conclusion Among patients hospitalized with a cIAI, 26.6% received ECT despite >50% lacking risk factors for resistance, and an only 10% prevalence of C3R in this cohort. This suggests that there remains an opportunity for carbapanem-sparing strategies. Further stratification of the risk for resistance is needed among patients with markers of high illness severity, such as those identified in our model. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]