Non-carbapenem Antibiotics Research Articles

Controversies in treating febrile infantile urinary tract infection caused by extended-spectrum beta-lactamase producing Enterobacteriaceae: an international multi-centre survey.

There is a lack of consensus in treating infants with extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) urinary tract infection (UTI) who demonstrate good clinical response to initial antibiotics within 48h. We conducted an international survey among paediatric nephrologists and fellows in training using a web-based questionnaire. A total of 232 centres across 77 countries participated in the survey. Second- or third-generation cephalosporins were the initial antibiotic of choice upon presentation in 63.8% of the centres. If the ESBL-E isolated from urine culture demonstrated in vitro susceptibility, 81.0% of respondents would continue the initial oral antibiotics. In contrast, there was considerable practice variation in the presence of in vitro resistance to the initial oral antibiotic. 19.0% would switch to a carbapenem group antibiotic, while 49.6% would change to a non-carbapenem antibiotic according to the sensitivity profiles. 22.8% would continue initial antibiotics based on satisfactory clinical response. The remaining 8.6% would choose other options. Similar emphasis on in vitro susceptibility result for the treatment was observed among centres who treated patients with intravenous antibiotics at UTI presentation. In the presence of a UTI with an ESBL-E, 50.0% centres would perform additional radiological investigations, and 61.2% would offer antibiotic prophylaxis to prevent further UTIs. There are significant variations in the management of UTI caused by ESBL-E bacteria between centres. In vitro susceptibility to the antibiotics remains an important management consideration. Antibiotics from the non-carbapenem groups seem to be the preferred option. Further studies are required to identify the optimal treatment regimen in this patient population.

P-881. A Retrospective Review of Enterobacter cloacae complex Bacteremia: 2019-2023

Abstract Background Enterobacter cloacae complex is one of the most common Enterobacterales considered at moderate to high risk for clinically significant AmpC production. AMP-C betalactamases confer resistance to broad spectrum cephalosporins and common beta-lactam betalactamases including Amoxicillin-Clavulanate and Piperacillin-Tazobactam. Carbapenems are often used empirically when this organism is isolated but there is a current gap in the literature regarding in which circumstances non-carbapenem antibiotics can be used safely for patients with enterobacter cloacae complex infections. The aim of this study was to examine independent predictors of mortality for patients with enterobacter cloacae complex bacteremia and identify patients which can appropriately receive non-carbapenem based therapy safely and effectively without negative impacts on mortality. Methods We conducted a retrospective analysis of 285 episodes of enterobacter cloacae complex bacteremia. The main outcome measure was mortality at 30 days.The χ2 or Fisher's exact test were used to compare categorical variables. To identify the independent risk factors of infection and mortality, a binary logistic regression model was used to control for the effects of confounding variables. Results Of 285 patients 17.5% (50) were deceased at 30 days, 110 patients received a beta-lactam betalactamase inhibitor combination initially and 80 patients received an initial broad spectrum cephalosporin. Of 209 patients for whom antibiotic data was available 73 were changed to a carbapenem within 24 hours of the initial blood culture being drawn. In univariate analysis only source was identified as a statistically significant risk factor for mortality at 30 days. In univariate and multivariate binary logistic regression analysis change to carbapenem within 24 hours of blood culture was not an independent risk factor of death at 30 days. Conclusion Change to carbapenem within 24 hours of cultures being taken was not an independent risk factor of 30 day mortality. Further studies are needed to determine in what group broad spectrum cephalosporins or beta-lactam betlactamase inhibitors are appropriate therapy for enterobacter cloacae. Disclosures All Authors: No reported disclosures

Elizabethkingia meningoseptica Carbapenem Resistance in Cerebrospinal Fluid Cultures of Patients Suspected of Bacterial Meningitis: A Case Report

Background: Elizabethkingia meningoseptica is a Gram-negative bacterium that rarely causes meningitis in children. These infections are often resistant to carbapenem antibiotics, making diagnosis and treatment more complicated. Case presentation: A 1-month-old male patient was treated to the PICU of Dr. M. Djamil General Hospital Padang with symptoms of decreased consciousness, seizures, and fever. The patient was diagnosed with bacterial meningitis and was referred from Sungai Dareh Regional General Hospital with previous therapy for 4 days. A cerebrospinal fluid examination showed increased protein and decreased glucose, and a CT scan showed hydrocephalus. The cerebrospinal fluid culture showed growth of Elizabethkingia meningoseptica which was resistant to imipenem and meropenem. The patient was treated with a combination of non-carbapenem antibiotics and recovered from meningitis. Conclusion: Carbapenem-resistant Elizabethkingia meningoseptica is a rare causative agent of meningitis in children. Early diagnosis and treatment with appropriate non-carbapenem antibiotics are essential to increase the chance of cure.

Efficacy of carbapenems and alternative antimicrobials for treating complicated urinary tract infections caused by third-generation cephalosporin-resistant gram-negative bacteria: A systematic review and meta-analysis of randomised controlled trials

Specific data concerning the efficacy of alternative antibiotics for carbapenems against complicated urinary tract infections (cUTIs) attributed to antimicrobial-resistant (AMR) uropathogens are lacking. This study aimed to assess the efficacy of carbapenems and non-carbapenem antibiotics in the clinical outcomes of cUTIs caused by AMR uropathogens. In this systematic review and meta-analysis, databases, including MEDLINE/PubMed, the Cochrane Library, Embase and ClinicalTrials.gov, were searched. The study eligibility criteria were research articles conducted as randomised controlled trials that evaluated the composite outcomes of cUTIs. Participants were adult patients with cUTIs caused by gram-negative uropathogens resistant to third-generation cephalosporins. The intervention involved a non-carbapenem class of antimicrobial agents with in vitro activities against gram-negative uropathogens resistant to third-generation cephalosporins. Two independent researchers assessed the risk-of-bias using the second version of the Cochrane risk-of-bias tool for randomised trials. The treatment effects on each outcome were estimated as a risk ratio (RR) with a 95% confidence interval (CI) using the random-effects model. Heterogeneity was assessed using the Cochrane Q-test and I2 statistics. Through database searches, 955 articles were retrieved. After screening the titles and abstracts, 52 articles were screened in full text. Finally, 12 studies met the inclusion criteria. No significant differences in efficacy were observed between alternative antibiotics and carbapenems (composite outcome, RR, 0.96; 95% CI, 0.63-1.49; I2=21%; low certainty of evidence). Alternative antibiotics had clinical efficacy similar to that of carbapenems for treating patients with cUTI caused by gram-negative uropathogens resistant to third-generation cephalosporins.

Efficacy of noncarbapenem therapy for the treatment of ceftriaxone-resistant Enterobacterales outside the urinary tract.

To determine the safety of noncarbapenem versus carbapenem antibiotics for treatment of adults with documented infection caused by ceftriaxone-resistant infections outside the urinary tract. Retrospective cohort of adult patients with a documented infection caused by an extended-spectrum β-lactamase (ESBL)-producing organism isolated between January 2018 and October 2021. An academic tertiary-care center. Adult patients with a documented infection caused by an ESBL-producing organism outside the urinary tract. The primary outcome was a composite of treatment failure defined as 30-day mortality, 30-day readmission, microbiological recurrence, and/or clinical worsening requiring antibiotic change. Secondary outcomes included differentiation of primary composite components and postantibiotic Clostridioides difficile infection (CDI). This study included 130 patients. The primary source of infections were bloodstream (67.7%) and caused by Escherichia coli (81.5%). Overall, 101 patients received carbapenem therapy and 29 received noncarbapenem therapy (NCT). NCT was comprised of mainly fluoroquinolones (18 of 29) followed by cefepime (7 of 29). Patients receiving NCT had shorter hospital stays (median, 7 days vs 9 days) and were more often discharged on antibiotics (79.3% vs 50.5%). We did not detect a significant difference in the primary composite outcome of treatment failure for carbapenem (23.8%) versus noncarbapenem treatment (24.2%; P = .967). Secondary outcomes included a numerically higher 30-day mortality rate in the noncarbapenem group compared to the carbapenem group: 4 (13.8%) of 29 versus 4 (3.9%) of 101. We did not detect a difference in rates of CDI. Noncarbapenem therapy may play a role for certain patients with infections caused by ESBL-producing organisms.

Concomitant Carbapenem and Colistin Resistance among Escherichia coli and Klebsiella pneumoniae Isolates from Patients Visiting a Hospital in Haryana, India

ABSTRACT Background: Increasing prevalence of carbapenem resistance among Enterobacterales, particularly Escherichia coli and Klebsiella pneumoniae, poses a serious public health threat globally. Furthermore, these bacteria exhibit multidrug resistance, making treatment of infections caused by them challenging. Colistin is one of the antibiotics used in the treatment of infections caused by carbapenem resistant Enterobacterales; however, its unrestricted usage has resulted in the emergence of colistin resistant strains. The present study was conducted to determine the prevalence of carbapenem resistance and co-resistance to carbapenem and colistin resistance among E. coli and K. pneumoniae isolated from various clinical specimens from patients attending various departments of a multispecialty teaching hospital in Haryana, India. Methods: A total of 597 isolates comprising 425 E. coli and 172 K. pneumoniae isolated between March 2019 to November 2021 were included in the study. The isolates were subjected to screening for the detection of carbapenemase production using carbapenem discs and a phenotypic test, that is, the CarbaNP test. Antibiogram of the carbapenem-resistant isolates was further analyzed by the Kirby–Bauer disc diffusion method and to evaluate colistin resistance, isolates were subjected to colistin broth disc elution test. Results: The prevalence of carbapenemase production among the E. coli and K. pneumoniae isolates by the screening test were detected to be 98/425 (23.1%) for E. coli and 90/172 (52.3%) for K. pneumoniae, whereas the CarbaNP test confirmed 93/425 (21.9%) and 84/172 (48.8%) of the two categories of bacterial isolates, thus showing a false positivity rate of 2.6% (n = 11) by screening test for the detection of carbapenemase production. Among the bacterial isolates, 3 (1.7%) comprising 1 (1.1%) E. coli and 2 (2.6%) K. pneumoniae were found to be dual carbapenem- and colistin-resistant strains. K. pneumoniae isolates showed higher resistance rates to non-carbapenem antibiotics compared to E. coli isolates. Conclusions: The emergence of bacteria with concurrent resistance to carbapenems and colistin is a serious concern as they are the last-resort drugs against multidrug-resistant and extensively drug-resistant bacteria.

Impact of selective reporting of antibiotic susceptibility testing results on meropenem prescriptions for the treatment of Pseudomonas aeruginosa infections after 2020 EUCAST criteria update: an observational study in a university hospital

BackgroundWe previously reported an increase in meropenem prescriptions for Pseudomonas aeruginosa infections in our hospital after the implementation of the 10th version of the EUCAST breakpoints table for P. aeruginosa in January 2020. As a consequence, antibiotic susceptibility testing results were adapted by masking meropenem for P. aeruginosa isolates susceptible to either ceftazidime, cefepime or piperacillin-tazobactam. We aimed to assess the changes in meropenem prescriptions after the implementation of the selective reporting.MethodsIn this retrospective single-centre observational study, we analysed antimicrobial therapies prescribed for P. aeruginosa infections after the susceptibility testing results have been made available over three periods: “before EUCAST update”, “after EUCAST update without selective reporting” and “after EUCAST update with selective reporting”, at Lausanne University Hospital, Switzerland. We collected epidemiological, microbiological and clinical data. The primary outcome was the prescription of meropenem to treat P. aeruginosa infections after the release of susceptibility testing results. Secondary outcomes were the use of increased dosage of non-meropenem anti-pseudomonal drugs, and IDs’ consultations rates after the release of susceptibility testing results.ResultsAmong the 457 patients included, 65 (14.2%) received meropenem: 5/148 (3.4%) before EUCAST update, 51/202 (25.3%) after EUCAST update without selective reporting, and 9/107 (8.4%) after EUCAST update with selective reporting. Supervision and counselling from IDs as well as the use of increased dosages of non-carbapenem antibiotics increased in both periods after EUCAST update, compared to the first period, respectively: 40.5% (60/148) versus 61.4% (124/202) versus 51.4% (55/107) (P < 0.001), and 57.9% (84/148) versus 91.1% (183/202) versus 90.7% (97/107) (P < 0.001).ConclusionsSelective reporting of antibiotic susceptibility testing results might decrease unnecessary meropenem prescriptions for the treatment of P. aeruginosa infections and could be part of multimodal antibiotic stewardship interventions.

Phenotypic and molecular characterization of IMP-producing Enterobacterales in Spain: Predominance of IMP-8 in Klebsiella pneumoniae and IMP-22 in Enterobacter roggenkampii.

ObjectivesLittle is known about IMP-producing Enterobacterales (IMP-Ent) in Europe. We analyzed at genomic and phenotypic level IMP-Ent isolates circulating in Spain in a 9-year period.Materials and methodsIMP-Ent isolates submitted to our reference laboratory were included. Antibiotic susceptibility was performed using microdilution method (EUCAST), and IMP-carbapenemase activity was measured with carbapenemase inhibitors, the β-CARBA method, the modified Hodge test (MHT), and the modified carbapenemase inhibition method (mCIM). All isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsFifty IMP-Ent isolates, collected from 19 hospitals in 13 Spanish provinces, were detected: Klebsiella pneumoniae (IMP-Kpn) (24; 48%), Enterobacter roggenkampii (13; 26%), Enterobacter hormaechei (8, 16%), Klebsiella oxytoca (two; 4%), Enterobacter asburiae (one, 2%), Serratia marcescens (one; 2%) and Escherichia coli (one; 2%). All isolates were positive by the MHT and β-CARBA tests; 48 (96%) were mCIM positive; 12 (24%) and 26 (52%) displayed positive inhibition with dipicolinic (meropenem) and EDTA (ertapenem), respectively. Five IMP-carbapenemase types were identified: IMP-8 (22; 44%), IMP-22 (17; 34%), IMP-13 (7; 14%), IMP-28 (two; 4%), and IMP-15 (two; 4%), predominating IMP-8 in K. pneumoniae and IMP-22 in E. roggenkampii. IMP-28 was exclusively identified in K. oxytoca and IMP-15 in E. hormaechei. Predominant STs were ST405 (29.2%), ST15 (25%) and ST464 (20.8%) in IMP-Kpn; ST96 (100%) in E. roggenkampii and ST182 (62.5%) in E. hormachei. Colistin and amikacin were the most active non-carbapenem antibiotics against IMP-Ent.ConclusionIMP-Ent isolates remain infrequent in Spain, although in recent years have been circulating causing nosocomial outbreaks, being IMP-8-producing K. pneumoniae and IMP-22-producing E. roggenkampii the most frequently detected in this study. Inhibition with EDTA or dipicolinic acid presented false negative results in some IMP-producing strains. Active microbiological and molecular surveillance is essential for a better comprehension and control of IMP-Ent dissemination.

Carbapenems versus Cephalosporin or Piperacillin-Tazobactam as Perioperative Antibiotic Prophylaxis in Liver Transplant Recipients with Model for End-Stage Liver Disease Scores of ≥30: A Retrospective Study in a Chinese Population.

ObjectivePerioperative prophylaxis, commonly with a third-generation cephalosporin plus ampicillin or piperacillin-tazobactam, is usually employed to prevent infections in liver transplantation (LT) recipients. Patients with a high Model for End-Stage Liver Disease (MELD) score have an increased infection risk after LT. However, whether carbapenems could be used as surgical prophylaxis in these high-risk patients remains unclear. Therefore, this study aimed at comparing the effectiveness of carbapenems with that of cephalosporin or piperacillin-tazobactam for surgical prophylaxis in high-risk LT recipients with a MELD score ≥30.Design or MethodsThis retrospective study included adult patients with a MELD score ≥30 who underwent LT between May 2018 and September 2020. We comparatively analyzed the infection rate and outcome between patients using cefoperazone-sulbactam or piperacillin-tazobactam and those using carbapenems as surgical prophylaxis.ResultsThis study included 105 LT recipients. Seventy-eight and 27 patients used non-carbapenem and carbapenem antibiotics, respectively, as surgical prophylaxis. The corresponding infection incidence rates within 30 days were 38.5% and 66.7% (p = 0.011). Multivariate analysis revealed that reoperation and the Child–Pugh score were independent risk factors for infections within 30 days after LT. The following four risk factors were associated with the 180-day post-LT survival: MELD score, vascular complication, intra-abdominal bleeding, and infection with carbapenem-resistant organisms (CROs). There was no significant difference in CRO infection incidence between the carbapenem and non-carbapenem groups (18.5% vs 11.5%; p = 0.345).ConclusionCarbapenem use as surgical prophylaxis was not associated with infection incidence within 30 days after LT, 180-day post-LT survival or CRO infection. Therefore, carbapenems are not superior to cephalosporin or piperacillin-tazobactam for perioperative antibiotic prophylaxis in LT recipients with a MELD score ≥30.

Impact of 2020 EUCAST criteria on meropenem prescription for the treatment of Pseudomonas aeruginosa infections: an observational study in a university hospital

We aimed to evaluate the impact of the 10th version of European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints table, where most antipseudomonal drugs but meropenem are now categorised as "Susceptible, increased exposure" and labelled I, on meropenem prescription for Pseudomonas aeruginosa infections. In this retrospective single-centre observational study, we analysed antimicrobial therapies prescribed after susceptibility testing in all consecutive adult patients treated for P.aeruginosa infections between 01.08.2019 and 30.07.2020 in Lausanne University Hospital, Switzerland. We collected epidemiological, microbiological, clinical data, antimicrobial therapy, and infectious diseases specialists (IDs) consultations' data. The primary outcome was the prescription of meropenem to treat P.aeruginosa infections after release of susceptibility testing results. Secondary outcomes were: the use of increased dosage for non-meropenem anti-pseudomonal drugs, and IDs' consultations rates after susceptibility testing was made available. Among the 264 patients included, 40 (15.2%) received meropenem, 3.4% (5/148) before EUCAST update versus 30.2% (35/116) after (p<0.001). Supervision and counselling from IDs and the use of increased dosages of non-carbapenem antibiotics also increased respectively (40.5% (60/148) vs 62.9% (73/116), P<0.001); (55.5% (76/148) vs 88.9% (72/116), P<0.001). Factors associated with these increments could not be adequately modelled. The change to 2020 EUCAST criteria might be associated with increased odds of meropenem prescription for the treatment of P.aeruginosa infections stressing the need of prescribers' education and the importance of antibiotic stewardship interventions.

1612. Evaluation of the Use of Ceftolozane/Tazobactam for the Treatment of ESBL-producing Enterobacterales Infections Using International Data from SPECTRA (Study of Prescribing Patterns and Effectiveness of Ceftolozane/Tazobactam Real World Analysis)

BackgroundThere is a paucity of data on outcomes of patients with severe ESBL-producing Enterobacterales infections treated with empiric or directed ceftolozane/tazobactam (C/T). This study looked at the treatment patterns and outcomes associated with C/T use in the treatment of ESBL-producing Enterobacterales.MethodsData were collected from an international cohort of 32 hospitals in 6 countries as part of SPECTRA, a retrospective multicenter database of C/T use globally, from 2016 – 2019. All adult patients with an ESBL positive Enterobacterales sterile site culture and treated with ≥ 48 hours of C/T were eligible. Outcomes assessed were clinical success, 30-day mortality from index event and readmission.ResultsThere were 59 patients with 121 ESBL positive isolates. Blood and urine were the most common sites of infection at 19.8% each, followed by respiratory (18.2%). E. coli (50%) and K. pneumoniae (30%) were the most common pathogens. On average patients had 2 positive ESBL isolates; median 1; range 1-15. Most patients had the same infection site and ESBL pathogen, however 13 had multi-site ESBL pathogens identified and only 2 had polymicrobial ESBL pathogens. Septic shock was observed in 14 (24%) patients; 29 (49%) were in the ICU at the onset of infection. The most common comorbid conditions were immunocompromised hosts (37%) and cardiac disease (32%). 29% of patients were transplant recipients, and 28% had a CrCl < 50 ml/min. In most patients (71%), C/T was given as directed therapy (i.e., once culture results were available). C/T was given prior to culture results (i.e., as empiric therapy) in 17 (29%) patients, of which 77% had clinical success. C/T dose was 1.5 g in 49%. Only 2 of 10 patients with a respiratory source received the currently licensed 3 g dose. Overall, clinical success was observed in 36 (61%) patients. 30-day mortality was 12%. Readmissions occurred in 5%, of which 2 were infection related.ConclusionThe role of newer non-carbapenem antibiotics in the treatment of severe ESBL infections is currently undefined. In a multinational patient database, C/T was found to be effective in severe infections caused by ESBL-producing Enterobacterales. Prospective studies are needed to further define the role of C/T in the setting of frequent drug-resistant Gram-negative pathogens.DisclosuresLaura A. Puzniak, PhD, Merck (Employee) Matteo Bassetti, MD, Shionogi Inc. (Advisor or Review Panel member) Pamela Moise, PharmD, Merck & Co., Inc. (Employee, Shareholder) David Paterson, Accelerate (Speaker’s Bureau)BioMerieux (Speaker’s Bureau)BioMerieux (Advisor or Review Panel member)Entasis (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Merck (Grant/Research Support)Merck (Speaker’s Bureau)Pfizer (Speaker’s Bureau)Shionogi & Co., Ltd. (Grant/Research Support)VenatoRx (Advisor or Review Panel member)

Outcomes of Extended-Spectrum Beta-Lactamase Gram-Negative Bacteremia Cases Treated With Carbapenem Versus Noncarbapenem Antibiotics

Background: The rising prevalence of infections caused by extended-spectrum β-lactamase (ESBL)–producing bacteria increases reliance on carbapenems, which intensifies selection pressure for the emergence of carbapenem-resistant Enterobacteriaceae (CRE). Whether noncarbapenem (nC) antibiotics can be safely used in this setting remains incompletely understood. Objective: To examine the safety of carbapenem stewardship in this population, we compared outcomes of uncomplicated ESBL bacteremia treated with a carbapenem to those treated with a noncarbapenem regimen. Methods: A retrospective chart review of patients with ESBL bacteremia from 2014 to 2018 in a 5-hospital regional health system was conducted. Patients aged &lt;18 years, with polymicrobial bacteremia, whose infections required a prolonged length of antibiotic therapy (LOT), or who died on antibiotic treatment or transitioned to hospice, were excluded. Groups were stratified based on the antibiotic regimen with the highest number of treatment days during the treatment course. Outcome measures included empiric and definitive length of therapy (LOT), 30-day all-cause mortality, 90-day readmission, recurrence of ESBL bacteremia, hospital length of stay (LOS), incidence of Clostridioides difficile infection (CDI) and adverse drug events, obtained by Wilcoxon rank-sum testing, χ2 test, and Fisher exact test, as applicable. Results: In total, 112 unique patients had ESBL bacteremia; 42 were excluded, leaving 70 for analysis. Of these, 57 were treated with a carbapenem regimen and 13 patients were treated with a noncarbapenem regimen: 9 ciprofloxacin, 3 gentamicin, 1 TMP-SMX. Patient baseline and antibiotic regimen characteristics were similar (Table 1). The most common organism was E. coli, and the most common source was urinary. A similar proportion of each group received ESBL-active empiric antibiotics. There were no significant differences in total effective antibiotic LOT, 30-day all-cause mortality, 90-day readmission, or recurrence of ESBL bacteremia (Table 2). A nonsignificant trend in hospital LOS was observed in the noncarbapenem group (11 vs 6 days; P = .055). Conclusions: Although the sample size was small, these multicenter data suggest that noncarbapenem treatment of ESBL bacteremia may be safe and effective. Pending confirmatory studies, ESBL bacteremia may be an important target for carbapenem stewardship.Funding: NoneDisclosures: None

Treatment and Outcomes of Children With Febrile Urinary Tract Infection Due to Extended Spectrum Beta-lactamase-producing Bacteria in Europe: TOO CUTE Study.

The prevalence of extended-spectrum beta-lactamase producing Εnterobacteriaceae (ESBL-PE) is increasing globally. ESBL-PE are an important cause of urinary tract infections (UTIs) in children. We aimed to characterize the clinical presentation, treatment and outcomes of childhood UTI caused by ESBL-PE in Europe. Multicenter retrospective cohort study. Children 0 to 18 years of age with fever, positive urinalysis and positive urine culture for an ESBL-PE uropathogen, seen in a participating hospital from January 2016 to July 2017, were included. Primary outcome measure: day of defervescence was compared between (1) initial microbiologically effective treatment (IET) versus initial microbiologically ineffective treatment (IIT) and (2) single initial antibiotic treatment versus combined initial antibiotic treatment. Clinical and microbiologic failure of initial treatment. We included 142 children from 14 hospitals in 8 countries. Sixty-one children had IET and 77 IIT. There was no statistical difference in time to defervescence for effective/ineffective groups (P = 0.722) and single/combination therapy groups (P = 0.574). Two of 59 (3.4%) and 4/66 (6.1%) patients exhibited clinical failure during treatment (P = 0.683) when receiving IET or IIT, respectively. Eight of 51 (15.7%) receiving IET and 6/58 (10.3%) receiving IIT patients (P = 0.568) had recurring symptoms/signs suggestive of a UTI. Recurrence of a UTI occurred 15.5 days (interquartile range, 9.0-19.0) after the end of treatment. Time to defervescence and clinical failure did not differ between IET/IIT groups. Non-carbapenem beta-lactam antibiotics may be used for the empiric treatment of ESBL febrile UTIs, until susceptibility testing results become available.

Urinary Tract Infections Caused by Community-Acquired Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in a Level III Hospital - A Retrospective Study

The emergence of β-lactamases producing bacteria is a problem worldwide, with increasing importance in communityacquired infections, especially in urinary tract infections. Data regarding the use of non-carbapenem antimicrobials in these infections are scarce. The aim of this study was to analyse the treatment and outcome of urinary tract infections caused by community-acquired β-lactamase-producing bacteria in children. Retrospective study performed in a level III paediatric hospital, between June 2007 and December 2017. All children with β-lactamase-producing Enterobacteriaceae identified in aseptically collected urine culture were included. A total of 175 urinary infections caused by β-lactamases producing bacteria were diagnosed, 34 (19%) were community-acquired: 25 Escherichia coli (74%), 4 Klebsiella pneumoniae (12%), 4 Proteus mirabilis (12%) and 1 Proteus vulgaris (3%). In 30 (88%) cases, it was the first urinary infection. After identification of the microorganism and antimicrobial susceptibility, 33 (97%) children were re-evaluated and 24 (71%) had a repeat urine culture, which was positive in three (13%). In six (18%) cases, antibiotic treatment was modified. Four (12%) children had another UTI in the following month. In 30 (88%) children, imaging was carried out, with no nephrourological malformations detected. In the last decade, about 20% of urinary infections caused by β-lactamase-producing Enterobacteriaceae were community-acquired with a relatively stable number of cases over the years. No nephro-urological malformations were identified in these children. Although the number of cases is small, the clinical and microbiological outcomes showed that most were successfully treated with non-carbapenem antibiotics, with low recurrence of new episodes of urinary tract infections.

Urban and agricultural soils in Southern California are a reservoir of carbapenem-resistant bacteria.

Carbapenems are last‐resort β‐lactam antibiotics used in healthcare facilities to treat multidrug‐resistant infections. Thus, most studies on identifying and characterizing carbapenem‐resistant bacteria (CRB) have focused on clinical settings. Relatively, little is still known about the distribution and characteristics of CRBs in the environment, and the role of soil as a potential reservoir of CRB in the United States remains unknown. Here, we have surveyed 11 soil samples from 9 different urban or agricultural locations in the Los Angeles–Southern California area to determine the prevalence and characteristics of CRB in these soils. All samples tested contained CRB with a frequency of <10 to 1.3 × 104 cfu per gram of soil, with most agricultural soil samples having a much higher relative frequency of CRB than urban soil samples. Identification and characterization of 40 CRB from these soil samples revealed that most of them were members of the genera Cupriavidus, Pseudomonas, and Stenotrophomonas. Other less prevalent genera identified among our isolated CRB, especially from agricultural soils, included the genera Enterococcus, Bradyrhizobium, Achromobacter, and Planomicrobium. Interestingly, all of these carbapenem‐resistant isolates were also intermediate or resistant to at least 1 noncarbapenem antibiotic. Further characterization of our isolated CRB revealed that 11 Stenotrophomonas, 3 Pseudomonas, 1 Enterococcus, and 1 Bradyrhizobium isolates were carbapenemase producers. Our findings show for the first time that both urban and agricultural soils in Southern California are an underappreciated reservoir of bacteria resistant to carbapenems and other antibiotics, including carbapenemase‐producing CRB.

1452. Is Carbapenem-Sparing Therapy as Effective as Carbapenems Against Extended-Spectrum β-Lactamase Producing Enterobacteriaceae in UTI?

BackgroundWith the emergence of carbapenem-resistant strains of Enterobacteriaceae, non-carbapenem antibiotics are suggested as the alternative treatment of extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae infection. In this study, efficacy of non-carbapenem antibiotics on acute pyelonephritis (APN) with ESBL-producing Enterobacteriaceae was compared with that of carbapenems.MethodsThe medical records of patients who had diagnosed to have acute pyelonephritis with ESBL-producing Enterobacteriaceae on their urine culture, from January 2011 to December 2018, were reviewed retrospectively. Patients were classified as carbapenem and non-carbapenem group according to the definitive antibiotics they had treated with.ResultsTotal number of patients was 141, including 112 (79.4%) who had received carbapenem, and 29 (20.6%) received non-carbapenem as definitive therapy against to APN with ESBL-producing Enterobacteriaceae. The duration of hospitalization was shorter for non-carbapenem group (median 9.93 days) than for carbapenem group (median 14.39 days) (P < 0.001). The duration of negative conversion of culture was shorter for carbapenem group (median 40.73 hours) than for non-carbapenem group (median 56.79 hours). There was no significant difference in time to febrile period and duration of definitive therapy between two groups.ConclusionNon-carbapenem therapy against APN with ESBL-producing Enterobacteriaceae has no significant difference in clinical outcome compared with carbapenem therapy.Disclosures All authors: No reported disclosures.

548. Carbapenem-Resistant Acinetobacter baumannii Antibiotic Susceptibility Testing and Antibiogram Formation, Connecticut 2017–2019

BackgroundCarbapenem-resistant Acinetobacter baumanii (CRAB) is an infectious disease threat with limited treatment options. Statewide CRAB reporting and isolate submission has been mandated in Connecticut (CT) since 2017, which allowed the creation of a statewide CRAB antibiogram to assist with empiric treatment options for CRAB.MethodsClinical CRAB isolates from 2017 through the first quarter of 2019 underwent carbapenemase and expanded susceptibility testing at the CT State Public Health Laboratory or the Antibiotic Resistance Laboratory Network regional lab for carbapenemase and expanded susceptibility testing. Susceptibility testing was done by broth microdilution and disk diffusion, and interpreted using Clinical and Laboratory Standards Institute breakpoints. Carbapenemase producers were detected by the modified carbapenem inactivation method. Polymerase chain reaction testing identified carbapenemase genes.ResultsOf the 64 CRAB isolates submitted, 40 remained after confirmation of carbapenem resistance, i.e., resistance to at least one carbapenem, and deduplication of patients. Of these, 19 were carbapenemase producers (CP), and 21 were non-carpabenemase producers (Non-CP). All isolates were non-susceptible to cefepime, ceftazidime, levofloxacin and all carbapenems. Colistin susceptibilities were available for 33 isolates, 32 (97%) of which were susceptible. Tobramycin susceptibilities were available for 31 isolates, only 10 (32%) of which were susceptible. Of the CP, all 15 were susceptible to colistin, but only 2 (14%) were susceptible to tobramycin. Of the Non-CP, 16 (89%) were susceptible to colistin, and 8 (47%) were susceptible to tobramycin. Most CRABs had a tigecycline minimum inhibitory concentration (MIC) of ≤2 μg/mL, with a higher proportion of Non-CP with lower MIC values than CP.ConclusionCRAB shows resistance to all carbapenems, and most non-carbapenem antibiotics except colistin and in rare circumstances tobramycin. Most CRAB isolates had tigecycline MICs of ≤2 μg/mL. The statewide antibiogram illustrates the lack of approved antibiotics for the treatment of CRAB, underscoring the importance of further antibiotic development for CRAB treatment. Disclosures All authors: No reported disclosures.

Prevalence and characteristics of methicillin-resistant staphylococci in goats on the island of Tenerife, Spain.

The aim of this study was to determine the prevalence of methicillin-resistant Staphylococcus (MRS) in healthy goats on the Island of Tenerife, Spain, as well as to identify the phenotypic and genotypic characteristics of the strains found. A cross-sectional prevalence study was conducted. A total of 158 goats from 15 different farms were sampled between September 2017 and January 2018. The percentage of positive samples of methicillin-resistant Staphylococcus aureus (MRSA) was 15.8% (25/158) and that of methicillin-resistant coagulase-negative staphylococci (MRCoNS) was 6.9% (11/158). All MRSA isolates from goats belonged to one clonal group showing Multi-Locus Sequence type 398. All strains studied (n = 36) were resistant to non-carbapenem beta-lactam antibiotics and susceptible to teicoplanin, linezolid, vancomycin, rifampicin, quinupristin-dalfospristin and mupirocine. In MRSA isolates, the highest percentage of resistance obtained, besides beta-lactam non-carbapenem antibiotics, was to trimethoprim-sulphamethoxazole and, in the case of MRCoNS isolates, to phosphomycin and erythromycin. A total of 12 resistance patterns were obtained, presenting differences between patterns obtained for MRSA and MRCoNS, with 7 different patterns for MRSA and 5 for MRCoNS. We therefore consider it essential to expand the epidemiological study of these strains of animal origin, as well as to increase surveillance and control measures at all stages of the food chain.

Antibiotics with activity against intestinal anaerobes and the hazard of acquired colonization with ceftriaxone-resistant Gram-negative pathogens in ICU patients: a propensity score-based analysis.

Intestinal colonization resistance is mainly exerted by commensal anaerobes. To assess whether exposure to non-carbapenem antibiotics with activity against intestinal anaerobes (namely, piperacillin/tazobactam, amoxicillin/clavulanate and metronidazole) may promote the acquisition of gut colonization with ceftriaxone-resistant Gram-negative bacteria (CFR-GNB) in ICU patients. All patients with a first stay >3 days in a single surgical ICU over a 30 month period were retrospectively included. Rectal carriage of CFR-GNB (i.e. ESBL-producing Enterobacteriaceae, AmpC-hyperproducing Enterobacteriaceae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and CFR Acinetobacter baumannii) was routinely screened for at admission then weekly. The impact of anti-anaerobe antibiotics was investigated in propensity score (PS)-matched cohorts of patients exposed and not exposed to these drugs and through PS-based inverse probability of treatment weighting on the whole study cohort, treating in-ICU death or discharge as competing risks for CFR-GNB acquisition. Among the 352 included patients [median ICU stay 16 (9-30) days, in-ICU mortality 12.2%], 120 (34.1%) acquired one or more CFR-GNB, mostly AmpC-hyperproducing Enterobacteriaceae (17.6%) and P. aeruginosa (14.8%). Exposure to anti-anaerobe antibiotics was the main predictor of CFR-GNB acquisition in both the PS-matched cohorts [adjusted HR (aHR) 3.92, 95% CI 1.12-13.7, P = 0.03] and the whole study cohort (aHR 4.30, 95% CI 1.46-12.63, P = 0.01). Exposure to other antimicrobials-especially ceftriaxone and imipenem/meropenem-exerted no independent impact on the likelihood of CFR-GNB acquisition. Exposure to non-carbapenem antibiotics with activity against intestinal anaerobes may predispose to CFR-GNB acquisition in ICU patients. Restricting the use of these drugs appears to be an antibiotic stewardship opportunity.

LptG contributes to changes in membrane permeability and the emergence of multidrug hypersusceptibility in a cystic fibrosis isolate of Pseudomonas aeruginosa.

PurposeIn the lungs of cystic fibrosis patients, Pseudomonas aeruginosa is exposed to a myriad of antibiotics leading to alterations in antibiotic susceptibility. This study identifies mutations resulting in hypersusceptibility in isogenic mutants of a P. aeruginosa clinical isolate, PA34.MethodsPA34 was exposed to subinhibitory concentrations of doripenem or meropenem during growth to mid‐log phase. Antibiotic susceptibility of surviving colonies was determined by agar dilution. Two carbapenem‐resistant colonies hypersusceptible to non‐carbapenem antibiotics were selected for further analysis. Antibiotic resistance gene expression was evaluated by RT‐rtPCR and OprD production by SDS‐PAGE. PA34 and isogenic mutants were evaluated with whole genome sequencing. Sequence variants were confirmed by Sanger sequencing, and cognate genes in eight carbapenem‐resistant clinical isolates hypersusceptible to non‐carbapenem antibiotics were sequenced. Lipopolysaccharide preparations of PA34 and hypersusceptible mutants were evaluated with ProQ‐Emerald stain.ResultsIsogenic mutants showed 4‐ to 8‐fold MIC increase for imipenem, meropenem, and doripenem. However, they were hypersusceptible (≥4‐fold MIC decrease) to aminoglycosides, fluoroquinolones, and non‐carbapenem β‐lactams. Expression of ampC or mex‐opr efflux pumps was unchanged, but OprD production was decreased. Mutations causing Q86H AlgU and G77C LptG amino acid substitutions and nonsense mutations within OprD were observed in both mutants. Lipopolysaccharide modifications were observed between isogenic mutants and PA34. Non‐synonymous mutations in LptF or LptG were observed in 6/8 hypersusceptible clinical isolates resistant to carbapenem antibiotics.ConclusionEvaluation of hypersusceptible mutants identified the association between lptG and a hypersusceptible phenotype. Modifications in lipopolysaccharide profiles suggests LptG modification interferes with lipopolysaccharide transport and contributes to hypersusceptibility.