Susceptibility To Cephalosporins Research Articles

Cefazolin as a predictor of urinary cephalosporin activity in indicated Enterobacterales.

Traditionally, cephalothin susceptibility results were used to predict the susceptibility of additional cephalosporins; however, in 2013-2014, the Clinical and Laboratory Standards Institute (CLSI) revisited this practice and determined that cefazolin is a more accurate proxy than cephalothin for uncomplicated urinary tract infections (uUTIs). Therefore, a cefazolin surrogacy breakpoint was established to predict the susceptibility of seven oral cephalosporins for Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis in the context of uUTIs. Clinical microbiology laboratories face several operational challenges when implementing the cefazolin surrogacy breakpoint, which may lead to confusion for the best path forward. Here, we review the historical context and data behind the surrogacy breakpoints, review PK/PD profiles for oral cephalosporins, discuss challenges in deploying the breakpoint, and highlight the limited clinical outcome data in this space.

Evaluation of predictors of third-generation cephalosporin non-susceptibility and factors affecting recurrence or death in bacteremia caused by Citrobacter freundii complex, Enterobacter cloacae complex, and Klebsiella aerogenes

Factors involved in the susceptibility of third-generation cephalosporins (3GCs) to bacteremia caused by Citrobacter freundii complex, Enterobacter cloacae complex, and Klebsiella aerogenes were investigated based on a case-case-control design. Antimicrobial therapy administered 30 days prior to bacteremia and hospitalization within 90 days were common risk factors for the 3GC susceptible and 3GC non-susceptible groups, while hospitalization from an institution or another hospital was a specific risk factor for the 3GC non-susceptible group. We also attempted to examine the factors affecting the clinical outcome of bacteremia. Hospitalization more than 14 days before the onset of bacteremia was an independent factor indicating poor clinical outcome. In contrast, the implementation of source control was an independent predictor of successful treatment. Although a longer hospital stay before the onset of bacteremia was associated with worse clinical outcomes, implementation of source control may have contributed to improved treatment outcomes for bacteremia.

Role of Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry for Species Identification of Acinetobacter Strains.

Introduction Acinetobacter species has become a leading cause of nosocomial infections in recent years. Objectives The aim of the study was to establish the usefulness of matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry (MS) for the identification of Acinetobacter species with respect to conventional biochemical methods and MicroScan WalkAway 96 Plus system and to compare the antibiotic susceptibility test results Kirby-Bauer disk diffusion method with MicroScan WalkAway 96 Plus automated identification and antimicrobial susceptibility testing system. Materials and Methods The study sample comprised 100 clinical isolates of Acinetobacter species. They were all identified using MALDI-TOF MS and compared with other two identification systems. Statistical Analysis Comparison of categorical variables by Fisher's exact test or Pearson's chi-square test was done. All statistical tools were two tailed, and a significant level p < 0.05 was used. All statistical tests were performed using SPSS v22.0 (Armonk IBM Corp., New York, United States). Cohen's kappa coefficients were also calculated and used as applicable. Results MALDI-TOF MS revealed 92 A. baumannii , 2 Acinetobacter nosocomialis , 3 Acinetobacter lwoffii , and 1 each was identified as Acinetobacter junii , Acinetobacter johnsonii , and Acinetobacter tandoii . There was moderate agreement between identification by MicroScan WalkAway and MALDI-TOF, and substantial agreement between conventional biochemical tests and MALDI-TOF. We found that there was a 100% categorical agreement with respect to susceptibility of aminoglycosides (amikacin, gentamicin, tobramycin) and cephalosporins (ceftazidime, cefepime, cefotaxime) between disk diffusion method and MicroScan WalkAway 96 Plus system. Total of 16 errors were observed. Conclusion Although MALDI-TOF MS could be useful to identify A. baumannii but not other species in the genus, it is a rapid, reliable method and can be routinely used in clinical laboratories.

Cephalosporin susceptibility of Staphylococcus aureus strains isolated from commercial rabbit and goats farms in Spain.

Antimicrobial drug resistance is an important problem that challenges veterinary clinicians to provide effective treatments without further spreading resistance to other animals and people. The most commonly used pharmacodynamic parameter to define potency of antimicrobial drugs is minimum inhibitory concentration (MIC). The aim of this study was to evaluate the antibiotic susceptibility of thirty-six strains of Staphylococcus aureus isolated from dairy goats with mastitis and rabbits with chronic staphylococcosis. Four cephalosporins were tested: cephalexin, cephalotin, cefonicid and ceftiofur. MIC tests were performed according to the microdilution broth method. The calculated values of sensitivity in goats and rabbits were 66.67% and 72.22% for cephalexin, 72.22 % and 94.44% for cefonicid, 77.78% and 94.44% for cephalotin and 77.78% and 100% for ceftiofur, respectively. For all antibiotics, MIC90 of S. aureus from rabbits were lower than MIC90 from goats. These data suggest that more antibiotics are used in goat milk production than in rabbit farming. According to MIC values obtained in this study, ceftiofur and cephalotin may be the best option for treating S. aureus infections in lactating goats. For rabbits, ceftiofur showed lowest MIC values, therefore, it could be an alternative to treatment the infections caused by S. aureus in this species.

Prevalence of Extended-Spectrum β-Lactamase-Resistant Genes in Escherichia coli Isolates from Central China during 2016-2019.

The emergence and dissemination of Escherichia coli (E. coli) strains that produce extended-spectrum beta-lactamases (ESBLs) represents a major public health threat. The present study was designed to evaluate the prevalence and characteristics of ESBL-producing Escherichia coli isolates from chickens in central China during 2016-2019. A total of 407 E. coli strains isolated from 581 chicken swabs were identified conventionally and analyzed for various cephalosporin susceptibility by disk-diffusion assay. ESBL-producing strains were screened using the double=disk synergy test and ESBL-encoding genes were carried out by PCR/sequencing. A total of 402 E. coli isolates exhibited strong resistance to first- to fourth-generation cephalosporins and monobactam antibiotics, especially cefazolin (60.69%), cefuroxime (54.05%), cefepime (35.14%), ceftriaxone (54.30%), and aztreonam (40.29%). Piperacillin/tazobactam (1.72%) was the most effective drug against the strains, but the resistance rates increased each year. Among the isolates, 262 were identified as ESBL producers and the isolation rates for the ESBL producers increased from 63.37% to 67.35% over the four years. CTX-M (97.33%) was the most prevalent type, followed by TEM (76.72%) and SHV (3.05%). The most common ESBL genotype combination was blaTEM + blaCTX-M (74.46%), in which the frequency of carriers increased steadily, followed by blaCTX-M + blaSHV (3.05%). In addition, the most predominant specific CTX-M subtypes were CTX-M-55 (48.47%) and CTX-M-1 (17.94%), followed by CTX-M-14 (11.01%), CTX-M-15 (8.02%), CTX-M-9 (6.11%), CTX-M-65 (4.58%), and CTX-M-3 (1.15%). Moreover, a novel multiplex qPCR assay was developed to detect blaCTX-M, blaTEM, and blaSHV, with limits of detection of 2.06 × 101 copies/μL, 1.10 × 101 copies/μL, and 1.86 × 101 copies/μL, respectively, and no cross-reactivity with other ESBL genes and avian pathogens. The assays exhibited 100% sensitivity and specificities of 85%, 100%, and 100% for blaCTX-M, blaTEM, and blaSHV, respectively. In conclusion, our findings indicated that ESBL-producing E.coli strains isolated from chickens in central China were highly resistant to cephalosporins and frequently harbored diversity in ESBL-encoding genes. These isolates can pose a significant public health risk. The novel multiplex qPCR method developed in this study may be a useful tool for molecular epidemiology and surveillance studies of ESBL genes.

Effect of Reduced Fluoroquinolone Use on Cephalosporin Use, Susceptibilities and Clostridioides difficile Infections.

Background: Overuse of fluoroquinolones has led to concerning rates of resistance, particularly among Gram-negative organisms. They are also highly implicated as a risk factor for Clostridioides difficile infection, and reports of other serious adverse events led to recommendations to restrict their use. Our health system began targeting the reduction in unnecessary fluoroquinolone prescribing in 2018, aiming to promote their safe and effective use. Broad-spectrum cephalosporins are often used as an alternative to fluoroquinolones. We sought to evaluate whether decreased fluoroquinolone use was associated with increased third- and fourth-generation cephalosporin use and whether these changes in utilization impacted other outcomes, including C. difficile infection (CDI) rates and susceptibilities among Gram-negative organisms. Methods: This retrospective descriptive analysis included adult patients who received a fluoroquinolone or broad-spectrum cephalosporin in a three-year time period across a large healthcare system. The primary objective was to evaluate the change in days of therapy (DOT) of fluoroquinolones and third- and fourth-generation cephalosporins. Secondary objectives included rates of resistance among common Gram-negative organisms, CDI, and analyses stratified by antibiotic indication. Results: Cephalosporin use increased by an average of 1.70 DOT/1000 PD per month (p < 0.001). Additionally, fluoroquinolone use decreased by an average of 1.18 DOT/1000 PD per month (p < 0.001). C. difficile infections decreased by 0.37 infections/10,000 patient-days per month (p < 0.001). Resistance to fluoroquinolones remained stable from 2018 to 2020, and a declining trend was observed in 2021. Conclusion: This study demonstrated that reduced fluoroquinolone use in a large healthcare system was associated with increased usage of broad-spectrum cephalosporins, decreased CDI and improvements in resistance patterns.

Screening for β-lactam resistance by penicillin G in the Streptococcus anginosus group challenged by rare strains with altered PBPs.

Streptococcus anginosus group (SAG) strains are common pathogens causing abscesses and bacteraemia. They are generally susceptible to β-lactams, which constitute first-line treatment. EUCAST recommends testing penicillin G susceptibility to screen for β-lactam resistance. Isolates categorized as susceptible (negative screening) can be reported as susceptible to aminopenicillins and third-generation cephalosporins. To assess the reliability of penicillin G resistance screening in predicting β-lactam resistance in SAG blood culture isolates, and to investigate isolates for which this test would be unreliable. We determined the susceptibility to penicillin G, amoxicillin and ceftriaxone of 90 SAG blood culture isolates, all with negative penicillin G resistance screening. β-Lactam-resistant strains were sequenced and compared with susceptible reference SAG strains. We detected two isolates displaying β-lactam resistance, especially to third-generation cephalosporins, despite negative screening for penicillin G resistance. For these isolates, amino acid substitutions were identified next to the essential PBP motifs SxxK, SxN and/or KS/TGS/T. Changes in these motifs have been previously linked to β-lactam resistance in Streptococcus pneumoniae. Our study suggests that aminopenicillin and third-generation cephalosporin susceptibility should be determined for SAG strains in the event of severe infection as screening for penicillin G resistance might not be sufficient to detect resistance mechanisms that predominantly affect cephalosporins. The PBP sequencing of resistant SAG strains allowed us to detect amino acid changes potentially linked to β-lactam resistance.

196. Increasing Bacteremia and Endovascular Infections due to Serratia marcescens: Implications for Evaluation and Treatment

Abstract Background While Serratia marcescens can cause bloodstream infections (BSI), endocarditis or other endovascular infections are historically rare and typically due to injection drug use (IDU). Given the rise in IDU nationwide, and limited evidence for managing non-HACEK gram-negative endocarditis, we examined trends in the epidemiology of Serratia BSI and characterized management strategies. Methods Our study was a retrospective analysis of adults admitted to UNC Health, a hospital network in North Carolina, from Apr 2014 to Mar 2021 with Serratia bacteremia. We used EMERSE, a program that searches free text in clinical notes, to identify those with ‘Serratia’ and either ‘bacteremia’ or ‘endocarditis’. This helped identify patients with microbiology obtained at outside hospitals. We performed chart review to confirm the Serratia BSI and collect demographic and clinical data. We tabulated yearly hospitalizations (Apr 1 to Mar 31), proportions of endovascular infections (endocarditis, cardiac device, vascular grafts), and described demographics and treatment approaches. Results We identified 97 patients by EMERSE and included 66 in analysis (Fig 1). 21 (32%) had endovascular infections and 21 (32%) overall were due to IDU (Table). Endovascular infections and BSIs increased over the period (Fig 2). Until 2018-2019, there were 0-10 Serratia BSIs yearly. In the final year, there were 37, 13 (37%) of which were endovascular infections. While we did not limit to S. marcescens, no other species were seen. 59/61 (97%) isolates with 3rd generation cephalosporin susceptibility reported were sensitive. 17/21 endovascular infections were endocarditis. 10/17 (59%) patients underwent valve replacement and 8/21 (38%) received dual antibiotic therapy for ≥ 6 weeks. Of the 10 attending infectious diseases follow-up visit, 6 were prescribed oral suppressive antibiotics after parenteral therapy. Figure 2. Serratia bloodstream infections (2014-2021) Table 1. Characteristics of Serratia bloodstream infections Conclusion Serratia BSI and endovascular infections are markedly increasing, with a large component due to IDU. Given the high proportion of endocarditis, echocardiography may be considered for patients with Serratia BSI, particularly those with IDU or prosthetic material. Further studies are needed to confirm this phenomenon and to establish evidence for optimal management of Serratia endocarditis. Disclosures Asher J. Schranz, MD, United HealthCare (Other Financial or Material Support, Spouse provides scientific review)

A Genome-Scale Antibiotic Screen in Serratia marcescens Identifies YdgH as a Conserved Modifier of Cephalosporin and Detergent Susceptibility.

Serratia marcescens, a member of the order Enterobacterales, is adept at colonizing health care environments and is an important cause of invasive infections. Antibiotic resistance is a daunting problem in S. marcescens because, in addition to plasmid-mediated mechanisms, most isolates have considerable intrinsic resistance to multiple antibiotic classes. To discover endogenous modifiers of antibiotic susceptibility in S. marcescens, a high-density transposon insertion library was subjected to sub-MICs of two cephalosporins, cefoxitin, and cefepime, as well as the fluoroquinolone ciprofloxacin. Comparisons of transposon insertion abundance before and after antibiotic exposure identified hundreds of potential modifiers of susceptibility to these agents. Using single-gene deletions, we validated several candidate modifiers of cefoxitin susceptibility and chose ydgH, a gene of unknown function, for further characterization. In addition to cefoxitin, deletion of ydgH in S. marcescens resulted in decreased susceptibility to multiple third-generation cephalosporins and, in contrast, to increased susceptibility to both cationic and anionic detergents. YdgH is highly conserved throughout the Enterobacterales, and we observed similar phenotypes in Escherichia coli O157:H7 and Enterobacter cloacae mutants. YdgH is predicted to localize to the periplasm, and we speculate that it may be involved there in cell envelope homeostasis. Collectively, our findings provide insight into chromosomal mediators of antibiotic resistance in S. marcescens and will serve as a resource for further investigations of this important pathogen.

Demographic and Epidemiological Characteristics Associated With Reduced Antimicrobial Susceptibility to Neisseria gonorrhoeae in the United States, Strengthening the US Response to Resistant Gonorrhea, 2018 to 2019.

Jurisdictions participating in Strengthening the US Response to Resistant Gonorrhea (SURRG) implemented specimen collection for culture and antimicrobial susceptibility testing from a sample of persons of all genders (at multiple anatomic sites) attending sexually transmitted disease clinics and community clinics. We describe the percentage and characteristics of patients whose isolates demonstrated reduced susceptibility (RS) to azithromycin, ceftriaxone, or cefixime. We included patients from clinics that participated in SURRG whose isolates underwent antimicrobial susceptibility testing by Etest. We defined RS as azithromycin minimum inhibitory concentrations (MICs) ≥2 μg/mL (AZM-RS), ceftriaxone MICs ≥0.125 μg/mL (CRO-RS), or cefixime MICs ≥0.25 μg/mL (CFX-RS). Patients with repeated infections appeared >1 time in the data. We calculated the frequency and percentage of patients with an isolate demonstrating RS by epidemiological characteristics. During the period 2018-2019, 10,013 patients from 8 jurisdictions provided 10,735 isolates. Among 10,013 patients, 11.0% (n = 1099) had ≥1 isolate with AZM-RS (range by jurisdiction, 2.5%-18.0%). Approximately 11.3% of 8771 of patients visiting sexually transmitted disease clinics and approximately 8.8% of 1242 patients visiting community clinics had an AZM-RS isolate. Nearly 6% of 1013 females had an AZM-RS isolate; among males, the percents of patients with an AZM-RS isolate were 17.7% among 4177 men who have sex only with men and 6.1% among 3581 men who have sex only with women. Few (0.4%) patients had isolates with CFX-RS (n = 40) or CRO-RS (n = 43). Although infections with reduced cephalosporin susceptibility were rare, AZM-RS infections were prevalent in this sample of patients in multiple jurisdictions and across gender and gender of sex partner categories.

Predicting Oral Beta-lactam susceptibilities against Streptococcus pneumoniae

BackgroundOral beta-lactam antimicrobials are not routinely tested against Streptococcus pneumoniae due to presumed susceptibility based upon penicillin minimum inhibitory concentration (MIC) testing. Currently, Clinical and Laboratory Standards Institute provides comments to use penicillin MIC ≤0.06 to predict oral cephalosporin susceptibility. However, no guidance is provided when cefotaxime MIC is known, leading to uncertainty with interpretation. The purpose of this study was to evaluate cefotaxime and penicillin MICs and their respective correlation to oral beta-lactam categorical susceptibility patterns.Methods249 S. pneumoniae isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-ToF) and then tested by broth microdilution method to penicillin, cefotaxime, amoxicillin, cefdinir, cefpodoxime, and cefuroxime.ResultsUsing Clinical and Laboratory Standards Institute (CLSI) non-meningitis breakpoints for cefotaxime, 240/249 isolates were classified as susceptible. Of the cefotaxime susceptible isolates, 23% of the isolates are misrepresented as cefdinir susceptible. Amoxicillin correlated well with penicillin MIC breakpoints with only 1 discordant isolate out of 249.ConclusionThe correlation between amoxicillin and penicillin creates a very reliable predictor to determine categorical susceptibility. However oral cephalosporins were not well predicted by either penicillin or cefotaxime leading to the possible risk of treatment failures. Caution should be used when transitioning to oral cephalosporins in cefotaxime susceptible isolates, especially with higher cefotaxime MICs.

Genomic and phenotypic diversity of Enterococcus faecalis isolated from endophthalmitis.

Enterococcus faecalis are hospital-associated opportunistic pathogens and also causative agents of post-operative endophthalmitis. Patients with enterococcal endophthalmitis often have poor visual outcomes, despite appropriate antibiotic therapy. Here we investigated the genomic and phenotypic characteristics of E. faecalis isolates collected from 13 patients treated at the University of Pittsburgh Medical Center Eye Center over 19 years. Comparative genomic analysis indicated that patients were infected with E. faecalis belonging to diverse multi-locus sequence types (STs) and resembled E. faecalis sampled from clinical, commensal, and environmental sources. We identified known E. faecalis virulence factors and antibiotic resistance genes in each genome, including genes conferring resistance to aminoglycosides, erythromycin, and tetracyclines. We assessed all isolates for their cytolysin production, biofilm formation, and antibiotic susceptibility, and observed phenotypic differences between isolates. Fluoroquinolone and cephalosporin susceptibilities were particularly variable between isolates, as were biofilm formation and cytolysin production. In addition, we found evidence of E. faecalis adaptation during recurrent endophthalmitis by identifying genetic variants that arose in sequential isolates sampled over eight months from the same patient. We identified a mutation in the DNA mismatch repair gene mutS that was associated with an increased rate of spontaneous mutation in the final isolate from the patient. Overall this study documents the genomic and phenotypic variability among E. faecalis causing endophthalmitis, as well as possible adaptive mechanisms underlying bacterial persistence during recurrent ocular infection.

Emergence of a Neisseria gonorrhoeae clone with reduced cephalosporin susceptibility between 2014 and 2019 in Amsterdam, The Netherlands, revealed by genomic population analysis.

BackgroundEmerging resistance to cephalosporins in Neisseria gonorrhoeae (Ng) is a major public health threat, since these are considered antibiotics of last resort. Continuous surveillance is needed to monitor the circulation of resistant strains and those with reduced susceptibility.ObjectivesFor the purpose of epidemiological surveillance, genomic population analysis was performed on Ng isolates from Amsterdam with a focus on isolates with reduced susceptibility to ceftriaxone.MethodsWGS data were obtained from 318 isolates from Amsterdam, the Netherlands between 2014 and 2019. Isolates were typed according to MLST, Ng Multi-Antigen Sequence Typing (NG-MAST) and Ng Sequence Typing for Antimicrobial Resistance (NG-STAR) schemes and additional resistance markers were identified. Phylogenetic trees were created to identify genetic clusters and to compare Dutch and non-Dutch MLST7827 isolates.ResultsMLST7363 and MLST1901 were the predominant strains having reduced susceptibility to ceftriaxone during 2014–16; MLST7827 emerged and dominated during 2017–19. NG-STAR38 and NG-MAST2318/10386 were predominant among MLST7827 isolates. MLST7827 reduced susceptibility isolates carried a non-mosaic 13.001 penA allele with an A501V mutation and porB1b G120K/A121D mutations, which were lacking in susceptible MLST7827 isolates. Phylogenetic analysis of all publicly available MLST7827 isolates showed strong genetic clustering of Dutch and other European MLST7827 isolates.ConclusionsMLST7827 isolates with reduced ceftriaxone susceptibility have emerged during recent years in Amsterdam. Co-occurrence of penA A501V and porB1b G120K/A121D mutations was strongly associated with reduced susceptibility to ceftriaxone. Genetic clustering of Dutch and other European MLST7827 isolates indicates extensive circulation of this strain in Europe. Close monitoring of the spread of this strain having an alarming susceptibility profile is needed.

Sputum susceptibilities in a nationwide veteran cohort

Respiratory infections are one of the most common causes of morbidity and mortality. This study examined antimicrobial susceptibility of common respiratory isolates from veterans. Sputum culture data from the Veteran Health Administration were obtained retrospectively between January 2009 and 2019. Cumulative antibiograms were constructed for bacterial isolate susceptibility. Sputum and bronchial cultures from approximately 10,345 veterans were included each year. Haemophilus influenzae has maintained high levels of susceptibility to third generation cephalosporins from 2009 (99.7%) to 2018 (97.2%). Third generation cephalosporin susceptibilities amongst Klebsiella pneumoniae have trended upward from 2009 to 2018 as well (79.1% vs 86.4%). In Pseudomonas aeruginosa isolates, there has been an increase in susceptibility rates to cefepime from 2009 to 2018 (79.6%, to 86.6%), gentamicin (81.5% to 89.1%), and piperacillin/tazobactam (86.5% to 90%). Fluoroquinolone susceptibilities amongst Escherichia coli have remained low but stable between 2009 and 2018. Third generation cephalosporin susceptibilities for S. pneumoniae improved slightly from 92.2% to 95% between 2009 and 2018 while susceptibility to azithromycin trended down slightly from 56.8% in 2009 to 51.7% in 2018 for S. pneumoniae. The antibiogram of sputum isolates from the VA Healthcare System were examined to determine changes in patterns of resistance over a decade of use. This large-scale study investigated nationwide sputum culture susceptibility trends. Avoidance of macrolides for empiric treatment of community acquired pneumonia and avoidance of fluoroquinolones for empiric treatment of hospital acquired or ventilator associated pneumonia may be warranted based on susceptibility trends.

Evaluation of MBT STAR-Cepha and MBT STAR-Carba kits for the detection of extended-spectrum β-lactamases and carbapenemase producing microorganisms using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Rapid and simple detection of extended-spectrum β-lactamase (ESBL) and carbapenemase is essential for antimicrobial treatment and infection control. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based MBT STAR-Cepha and MBT STAR-Carba kits have been developed with simplified MBT STAR-BL operations. However, the utility of these kits has not been fully examined in clinical microbiology laboratories. In this study, we evaluated the utility of MALDI-TOF MS-based MBT STAR-Cepha and MBT STAR-Carba kits to detect ESBL and carbapenemase-producing bacteria, and compared it with the conventional broth microdilution test and PCR amplification assay. We found that the MBT STAR-Cepha kit efficiently distinguished resistant strains of third-generation cephalosporin susceptibility phenotypes and non-SHV-type ESBL producers. In the receiver operating characteristic analysis, the area under the receiver operating characteristic curve (AUC) for detecting third-generation cephalosporin resistance using the MBT STAR-Cepha kit was 0.97–1.00, but the AUC for detecting ESBL producers was 0.64. In addition, we showed that the MBT STAR-Carba kit enabled the accurate detection of antimicrobial resistance by IMP-type carbapenemase producers. The AUC for detecting carbapenemase producers was 1.00. The results suggested that the target bacterial strains, antimicrobial susceptibility phenotypes, and resistance genes were important for the utility of the MALDI-TOF MS-based MBT STAR-Cepha and MBT STAR-Carba kits in bacterial routine diagnostics.

Surrogate testing of oral third-generation cephalosporin susceptibility to common uropathogens

Cefazolin susceptibility of urine isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis predicts susceptibility to oral cephalosporins, but cefazolin-resistant isolates may be susceptible to oral third-generation cephalosporins. Among 194 urine isolates, we found >95% categorical agreement among oral third-generation cephalosporins. Surrogate testing of cefpodoxime for cefdinir, and vice versa, resulted in no major or very major errors, while combinations involving cefixime produced rare major and very major errors.

180. Klebsiella pneumoniae and K. oxytoca Bacteremia: Differences in Host, Source, and Antibiotic Susceptibility

Background Klebsiella species (KS) bloodstream infection (BSI) is often caused by K. pneumoniae (KP). K. oxytoca (KO) is emerging and implicated in antibiotic-associated right-sided colitis. We compared the clinical and microbiological characteristics of KP and KO.MethodsWe reviewed blood culture (BC) results (January 1, 2010–December 31, 2017), selected patients with KS in ≥1 BC, reviewed their medical records, abstracted patient demographics, source of bacteremia, antibiotics susceptibility, and outcome. Each patient was counted once. We compared KP and KO cases. All differences were assessed by the chi-square test and regression analysis, using SPSS.ResultsWe encountered KS in 975/14,256 (6.8%) positive BC, representing 611 BSI including 537 KP-BSI (484 patients) and 55 KO-BSI cases (54 patients); each patient was counted once. Mean age and prevalence of diabetes and most comorbidities were similar but KO was less frequent in African Americans (40.7% vs. KP [61.3%]; P = 0.005) and in patients with neurological debility (Stroke, paraplegia, multiple sclerosis; 11.1% vs. KP [24.8%]; P = 0.03). KO BSI was more frequent in IVC BSI and was absent in pneumonia-associated BSI (table). Antibiotic resistance was rare among KO isolates except for cefazolin-intermediate susceptibility (42.6% vs. 1.7%; P < 0.001). CREs were limited to KP. Logistic regression analysis confirmed KO link to IVC (OR = 3.57; 95% CI: 1.89, 6.76; P < 0.001) and Caucasian race (OR = 2.46; CI: 1.37, 4.42; P = 0.003). Mortality rate was comparable (28.1% [KP] vs. 35.2% [KO]; P = 0.3). Source and antibiotic susceptibility (%) in K. pneumoniae and K. oxytoca bacteremia K. pneumoniae K. oxytoca P SourceIVC12.833.3<0.001UTI34.924.10.1Soft/tissue bone8.711.10.6Abdomen21.314.80.4Pneumonia8.300.03Antibiotics resistanceCefazolin28.620.40.1Ceftriaxone25.25.60.001Ciprofloxacin25.61.9<0.001Gentamicin18.21.90.001TMP/SMX25.41.9<0.001ESBL 25.63.7<0.001CRE4.700.1ConclusionKO and KP BSI differ in the type of host and source, suggesting different colonization dynamics. KO remains antibiotic-susceptible but might be cefazolin less susceptible. Prospective studies are needed to confirm differential cephalosporin susceptibility and delineate host–pathogen interactions.Disclosures All authors: No reported disclosures.

Impact of Ceftazidime Use on Susceptibility Patterns in the Neonatal Intensive Care Unit.

Ceftazidime use in the neonatal intensive care unit (NICU) has increased after a cefotaxime shortage. The impact of this change is unknown. The purpose was to assess the effect of increased ceftazidime use on susceptibilities of Gram-negative organisms in the NICU. Retrospective study of Gram-negative isolates identified in blood, urine, cerebrospinal fluid, tracheostomy, abdominal fluid and pleural fluid cultures from a single-center NICU over a 5-year period. Duplicate cultures that occurred within 90 days were noted. Pre- and postshortage periods were defined based on cessation of cefotaxime. Third- and fourth-generation cephalosporin susceptibility rates were compared between periods, as well as rates of extended-spectrum beta-lactamase (ESBL) Escherichia coli and Klebsiella species. Analysis included 666 isolates. Twelve (1.8%) were duplicate isolates that occurred after a 90-day period. The preshortage period included 464 (69.7%) isolates, and the postshortage included 202 (30.3%). No significant differences in susceptibility rates were noted when excluding duplicates. No difference in ESBL rates for E. coli were noted between periods (3.8% vs. 4.9%, P =1.000). No ESBL-positive Klebsiella species were identified. A post-hoc analysis of duplicate isolates demonstrated significant lower susceptibility rates for Pseudomonas aeruginosa to ceftazidime (risk ratio 0.58; 95% CI: 0.43-0.79) and cefepime (risk ratio 0.66; 95% CI: 0.51-0.86). Ceftazidime use did not appear to affect susceptibility rates for third- and fourth-generation cephalosporins for most Gram-negative organisms in the short-term of 1.5 years. However, susceptibility rates for P. aeruginosa decreased when evaluating duplicate isolates. Long-term monitoring is needed to assess the true impact.

Decreased Cephalosporin Susceptibility of Oropharyngeal Neisseria Species in Antibiotic-using Men Who Have Sex With Men in Hanoi, Vietnam.

Neisseria gonorrhoeae (NG) infections are a global health burden. NG resistance to cephalosporins, which is increasingly reported, is an imminent threat to public health. Many hypothesize that commensal Neisseria species are an important reservoir for genetic material conferring antimicrobial resistance in NG; however, clinical data are lacking. Men who have sex with men (MSM) in Hanoi, Vietnam, completed a questionnaire regarding antibiotic use. We collected pharyngeal specimens, cultured Neisseria species, and measured minimum inhibitory concentrations (MICs) to ciprofloxacin, cefixime, ceftriaxone, and cefpodoxime. Using MIC criteria for antimicrobial susceptibility in NG, we categorized the Neisseria species and compared mean MIC levels between different antibiotic user groups. Of 207 participants, 38% used at least 1 antibiotic in the past 6 months; 52% without a prescription. A median of 1 Neisseria species was cultured from each participant (range, 1-4) with 10 different Neisseria species identified overall. The proportion of Neisseria with reduced susceptibility to ciprofloxacin was 93%, cefpodoxime 84%, cefixime 31%, and ceftriaxone 28%. Antibiotic use within the past month was strongly associated with Neisseria species having increased MICs to cefixime, ceftriaxone, and cefpodoxime (mean MIC ratios of 6.27, 4.11, and 7.70, respectively), compared with those who used antibiotics between 1 and 6 months prior (P < .05, all comparisons). MSM in our study often used antibiotics without a prescription. At least 1 commensal Neisseria species colonized all men. Recent use of any antibiotics may select for oropharyngeal Neisseria species with antimicrobial resistance. The normal flora of the oropharynx may be an important source of antimicrobial resistance in Neisseria gonorrhoeae.

Impact of rapid diagnostic tests on the management of patients presenting with Enterobacteriaceae bacteremia

ObjectivePathogens are usually identified from blood cultures using a two-step procedure: Gram staining on the day of bacterial growth (D0), followed by identification and susceptibility testing the following day (D1). We aimed to evaluate the use of rapid tests performed on D0 in patients presenting with Enterobacteriaceae bacteremia. Patients and methodsPatients with≥1 positive monomicrobial blood culture with Gram staining suggestive of an Enterobacteriaceae were prospectively included. Two successive strategies were evaluated: i) conventional strategy (CS), ii) combination of a rapid identification test and third-generation cephalosporin susceptibility testing (rapid strategy, e.g. RS). ResultsEighty-three patients were included (CS=42; RS=41). Compared with CS, the median delay of identification was significantly shorter with RS (22 hours [20–27] vs. 47 hours [42–53]; P<0.001). Patients in the RS group more frequently received an effective (82.9% vs. 73.8%, P=0.43) and appropriate (70.7% vs. 54.7%, P=0.17) antibiotic therapy on D1. Moreover, all five RS patients infected with a non-susceptible strain received an effective therapy on D1 versus only three of eight CS patients. ConclusionsUse of rapid testing was associated with a reduced time to result availability. This strategy should be useful to initiate an early effective and appropriate therapy and to improve the care of patients.