Ceftriaxone-nonsusceptible Isolates Research Articles

1305. Antimicrobial Activity of Ceftaroline and Comparator Agents against Ceftriaxone-Non-Susceptible Streptococcus pneumoniae from the United States (2008-2020)

1305. Antimicrobial Activity of Ceftaroline and Comparator Agents against Ceftriaxone-Non-Susceptible <i>Streptococcus pneumoniae</i> from the United States (2008-2020)

305. Prevalence of Ceftriaxone Susceptible, Piperacillin-tazobactam Non-susceptible Escherichia coli Bacteremia in Patients with Hematologic Malignancy

BackgroundPiperacillin-tazobactam (TZP) is common empiric and targeted therapy for gram-negative bacteremia in patients with hematologic malignancy. Resistance to TZP tends to occur concurrently with ceftriaxone (CRO) resistance; however, the prevalence of TZP nonsusceptibility in CRO susceptible Escherichia coli (E. coli) in patients with hematologic malignancy is unknown. Therefore, we sought to determine the prevalence of TZP nonsusceptible, CRO susceptible E. coli bacteremia at a cancer center.MethodsThis is a retrospective cohort study of adult (age > 18) patients with E. coli bacteremia admitted to the Leukemia or Stem Cell Transplant (SCT) services at The University of Texas MD Anderson Cancer Center (MDACC) between 8/2016 and 7/2019. Isolates were categorized according to current CLSI resistance breakpoints. A first isolate was defined as the first positive blood culture and subsequent episodes of bacteremia were defined as any E. coli isolate obtained at least 24 hours after the first negative blood culture.ResultsThe overall prevalence of TZP resistant CRO susceptible E. coli from 404 isolates was 7.7% and varied by service. There was a higher prevalence in the Leukemia service compared to SCT, 9.8% vs 2.5%, respectively (p < 0.01). 46% of isolates were CRO nonsusceptible, of which 91% were extended-spectrum beta-lactamase (ESBL) producers, identified by Vitek 2 or Accelerate Pheno. The TZP MIC50 was 4ug/ml, MIC90 was 128ug/ml, with an MIC range of 3ug/ml to ≥ 256ug/ml. The TZP MIC distribution varied based upon CRO phenotype. In CRO susceptible isolates the MIC50 and MIC90 were 4ug/ml and 64ug/ml, respectively, compared to 8ug/ml and 128ug/ml in CRO nonsusceptible isolates (p < 0.01). TZP resistance was more common in CRO nonsusceptible isolates (31.6% vs 12.0%, p < 0.01) and was more frequent with subsequent episodes of bacteremia compared to the first (39.5% vs 20.1%, p < 0.01).ConclusionIn patients with hematologic malignancy and E. coli bacteremia, TZP resistance is common with significant variations by CRO phenotype. TZP resistance becomes more common with subsequent episodes of bacteremia compared to the first. The clinical implications and genetic cause of this phenotype is currently unknown and warrants further investigation.Disclosures All Authors: No reported disclosures

Osteoarticular Infections Caused by Streptococcus pneumoniae in Children in the Post-Pneumococcal Conjugate Vaccine Era.

Pneumococcal osteoarticular infections (OAIs) are an uncommon manifestation of invasive pneumococcal disease (IPD). We describe the demographic characteristics, hospitalization rate, serotype distribution and antibiotic susceptibility of children with pneumococcal OAI over a 16-year period. We identified patients ≤18 years old with pneumococcal OAI at 8 children's hospitals in the United States (2000-2015). Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. We identified 97 (3.3%) patients with pneumococcal OAI out of 2943 patients with IPD. Over 60% of the children were <2 years old. Septic arthritis (56.7%, 55/97) was the most common pneumococcal OAI, followed by osteomyelitis (25.8%, 25/97) and septic arthritis with concomitant osteomyelitis (17.5%, 17/97). Hospitalization for pneumococcal OAI overall decreased from 6.8 [95% confidence interval (CI): 5.2-8.6] to 4.4 (95% CI: 3.0-6.3) per 100,000 admissions from 2000-2009 to 2010-2015 (-35%, P = 0.05). Hospitalization for pneumococcal OAI caused by PCV13 serotypes decreased from 4.6 (95% CI: 3.4-6.2) to 0.9 (95% CI: 0.3-1.9) per 100,000 admissions from 2000-2009 to 2010-2015 (-87%, P < 0.0001). Overall, 12% of isolates had a penicillin minimal inhibitory concentration> 2 µg/mL, 3% a ceftriaxone minimal inhibitory concentration> 1 µg/mL and 15% were clindamycin resistant; these proportions remained unchanged after the introduction of PCV13. Serotypes 19A and 35B were responsible for penicillin and ceftriaxone nonsusceptible isolates in 2010-2015. Pneumococcal OAI represents 3% of all IPD, affecting mainly healthy infants and young children. Hospitalization for pneumococcal OAI caused by PCV13 serotypes dramatically decreased (-87%) after the introduction of PCV13.

Impact of CLSI and EUCAST Cefepime breakpoint changes on the susceptibility reporting for Enterobacteriaceae

ObjectiveWe analyzed the effects of different cefepime MIC breakpoints on Enterobacteriaceae cefepime susceptibility and the presence of AmpC and extended-spectrum β-lactamase (ESBL) genes within the cefepime MIC interpretative categories. MethodsUsing Enterobacteriaceae susceptibility data from 2013 comparisons of MIC breakpoints were performed using Pearson's chi-squared test. Molecular testing on a subset of isolates was done. ResultsAmong 3784 non-duplicate clinical isolates, cefepime susceptibility decreased from 97.6% to 96.1% to 93.7% for CLSI 2013, CLSI 2014, and EUCAST 2011, respectively. In ceftriaxone non-susceptible isolates, cefepime susceptibility decreased from 79% to 66% (P<0.0001) using CLSI 2013 and 2014, respectively, which was greater and statistically significant for Escherichia coli and Klebsiella spp. but not for Enterobacter spp. (P=0.06). Isolates with MIC ≤1μg/mL more often harbored AmpC (77%) than ESBL (18%) genes. ConclusionsLower cefepime MIC breakpoints decrease cefepime susceptibility for isolates harboring ESBLs, while sparing the majority of those with AmpCs.

Factors Associated with Ceftriaxone Nonsusceptibility of Streptococcus pneumoniae: Analysis of South African National Surveillance Data, 2003 to 2010

It is important to monitor β-lactam antimicrobial nonsusceptibility trends for Streptococcus pneumoniae to inform empirical treatment guidelines. In this study, we describe penicillin and ceftriaxone susceptibility trends using national laboratory-based pneumococcal surveillance data from 2003 to 2010. A sentinel enhanced-site patient subset (2009 to 2010) contributed to the risk factor and mortality analyses. We included 9,218 invasive pneumococcal disease (IPD) cases for trend analyses and 2,854 IPD cases for risk factor and mortality analyses. Overall, we detected no significant changes in penicillin (patients <5 years of age, P = 0.50; patients ≥ 5 years of age, P = 0.05) or ceftriaxone nonsusceptibility rates (patients <5 years of age, P = 0.21; patients ≥ 5 years of age, P = 0.60). Factors associated with ceftriaxone nonsusceptibility on multivariate analysis were an age of <5 years (<1 year of age: adjusted odds ratio [aOR], 2.87; 95% confidence interval [CI], 1.70 to 4.86; 1 to 4 years of age: aOR, 2.58; 95% CI, 1.53 to 4.35, versus 25 to 44 years of age), province (Gauteng [aOR, 2.46; 95% CI, 1.26 to 4.84], and Northern Cape [aOR, 4.52; 95% CI, 1.95 to 10.52] versus KwaZulu-Natal), β-lactam use within 24 h preceding admission (aOR, 2.52; 95% CI, 1.41 to 4.53), and 13-valent vaccine serotypes (aOR, 51.64; 95% CI, 7.18 to 371.71). Among patients ≥ 5 years of age with meningitis who were treated according to current guidelines, HIV-infected patients (aOR, 2.94; 95% CI, 1.32 to 6.54) and patients infected with ceftriaxone-nonsusceptible isolates (aOR, 3.17; 95% CI, 1.27 to 7.89) had increased mortality rates. Among children <5 years of age with meningitis, mortality was increased in HIV-infected patients (aOR, 3.04; 95% CI, 1.40 to 6.56) but not in those with ceftriaxone-nonsusceptible isolates. Penicillin and ceftriaxone nonsusceptibility remained stable over the study period. Ceftriaxone nonsusceptibility was associated with increased mortality among patients ≥5 years of age with meningitis. The introduction of a pneumococcal conjugate vaccine may reduce ceftriaxone-nonsusceptible meningitis.

Antimicrobial Resistance and Molecular Epidemiologic Characteristics ofNeisseria gonorrhoeaeIsolated from Korea in 2013

Background: Antimicrobial resistance of Neisseria gonorrhoeae has become a serious problem worldwide, and ceftriaxone non-susceptible isolates have been recently reported from Japan and Europe. In this study, we evaluated the antimicrobial susceptibilities and molecular epidemiological characteristics of isolates from Korea in 2013. Methods: Sixty strains of N. gonorrhoeae were collected from Korean patients and prostitutes. Antimicrobial susceptibility was tested by the agar dilution and disk diffusion methods. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was performed in order to determine the molecular epidemiologic relatedness. Results: All of isolates were non-susceptible to penicillin G and tetracycline, and the rate of ciprofloxacinresistant isolates was 95% in 2013. The MICs of ceftriaxone were within the susceptible range for all isolates, but one isolate non-susceptible to cefixime (MIC=0.5 μg/mL) was encountered. The isolates with decreased susceptibility (MIC≤0.12 μg/mL) to cefixime or ceftriaxone accounted for 10% and 14% of the isolates tested, respectively. In NG-MAST analysis, 40 different STs were encountered among the 59 isolates. Isolates that belonged to tbpB110 showed higher cefixime and ceftriaxone MICs (0.12-0.5 μg/ mL) as well as cefixime resistance. Conclusion: Most of the N. gonorrhoeae isolates showed susceptibility to spectinomycin and cephalosporins. Due to the emergence of isolates that are non-susceptible to cefixime and the prevalence of isolates with the tbpB110 allele belonging to ST1407, which cause cefixime and ceftriaxone treatment failure in successful global clones of N. gonorrhoeae, a continuous nationwide antimicrobial surveillance program is required to monitor the emergence of cephalosporin resistance in N. gonorrhoeae. (Ann Clin Microbiol 2013;16:182-187)

Eleven-Year Surveillance of Antibiotic Resistance in Streptococcus pneumoniae in Casablanca (Morocco)

To analyze trends of antibiotic resistance rates in Streptococcus pneumoniae from 1998 to 2008 in Casablanca (Morocco). The antibiotic resistance levels of 955 consecutive nonduplicate isolates were studied using E test and disc diffusion methods. Results were interpreted following Clinical and Laboratory Standards Institute guidelines (2005). Analysis was done according to three periods (1998-2001; 2002-2005; 2006-2008), age, and site of infection. Penicillin nonsusceptibility (PNS) increased significantly over time (15.6%, 17.8%, and 24.8%; p=0.003). Levels of PNS have changed as well: in 2006-2008, 9.1% of the isolates had an MIC ≥2 μg/ml versus 7.7% in 2002-2005 and 3.4% in 1998-2001. The PNS increase was particularly marked in pediatric isolates (21.4%, 25.5%, and 43.3%; p=0.001). There was no significant difference between the rates of PNS in invasive and noninvasive isolates from children, whereas in adults noninvasive isolates were more penicillin nonsusceptible. Amoxicillin and ceftriaxone nonsusceptible isolates were very rare. An increase of resistance rates was also noticed for erythromycin (9.4%, 12.2%, and 14.4%), tetracycline (20%, 18.6%, and 30.5%), and chloramphenicol (5.6%, 5.6%, and 8.1%). Trimethoprim-sulfamethoxazole resistance rates remained stable (22.8%, 20%, and 23.8%). Proportions of dual nonsusceptibility to penicillin and erythromycin, increased from 5.6% to 8.9%. Multiple drug resistance (resistance to 3 or more antibiotic classes) was found in 0%, 2.4%, and 7.7% of all isolates, respectively. The results reported here maybe useful for guiding update of treatment recommendations and suggest the need for continuous surveillance. Increase of antibiotic resistance correlated with antibiotic consumption, stressing the need for elaboration of antibiotic policy in Morocco.

Invasive pneumococcal disease in Portugal prior to and after the introduction of pneumococcal heptavalent conjugate vaccine

The rates of invasive pneumococcal disease (IPD), serotype distribution and antimicrobial susceptibility prior to and after the introduction of the heptavalent pneumococcal conjugate vaccine in Portuguese children were evaluated. The changes in incidence of IPD in children under 1 year old between the two periods of the study was not significant (P=0.53), despite the 21% decline. In children under 18 years old there was a 27.7% decrease in vaccine serotypes. All nonvaccine serotypes increased 71.4%. The decrease in vaccine serotypes was more impressive during the first year of life (-54.8%) than for children between 1 and 5 years of age (-19.1%). Among children under 1 year old, penicillin nonsusceptible isolates declined between the two periods of the study (47.2% vs. 25.0%) (P=0.03), as did those of cefotaxime and ceftriaxone nonsusceptible isolates. No changes were observed for isolates nonsusceptible to tetracycline and macrolides. The serotypes of these nonsusceptible isolates differed after the introduction of vaccine (P=0.01). Multiresistance increased 57.1% after the introduction of vaccine. Multiresistant isolates with vaccine serotype declined 42.9% (P<0.001), and nonvaccine serotypes appeared during the vaccination period (P<0.001). These findings suggest a replacement of vaccine serotypes by nonvaccine serotypes, mainly among nonsusceptible isolates.

Outbreak of Dysentery Associated with Ceftriaxone-Resistant Shigella sonnei : First Report of Plasmid-Mediated CMY-2-Type AmpC β-Lactamase Resistance in S. sonnei

We document the first report of plasmid-encoded CMY-2-type AmpC beta-lactamase identified among Shigella sonnei isolates resistant to ceftriaxone and obtained after an outbreak of bacillary dysentery in Taiwan. One hundred eighty-two children in two elementary schools in Yu-Li, Taiwan, where an outbreak occurred after a typhoon hit this area in 2001, were enrolled in this study. Clinical and epidemiologic data on the infected children were collected. Pulsed-field gel electrophoresis (PFGE) was performed on the isolates to determine the genetic relatedness of outbreak strains. Plasmid analysis and PCR were performed to identify beta-lactamase genes responsible for ceftriaxone resistance. Forty-seven children from the two elementary schools were culture positive for S. sonnei in this outbreak. Twenty-three children were asymptomatic. Of the total isolates 55.3% were resistant to ampicillin. One hundred percent of the isolates obtained from children in school A were initially susceptible to both ampicillin and ceftriaxone. Of isolates obtained from school B 96.2% were nonsusceptible to ceftriaxone. However, two isolates from school A developed resistance to ampicillin during the course of treatment. All 18 available isolates showed closely related PFGE patterns (4, 4a, 4b, and 4c). CMY-2-type AmpC beta-lactamase was responsible for ceftriaxone resistance in ceftriaxone-nonsusceptible isolates; Southern blot hybridization confirmed that such a resistance gene was located on the plasmid. This is the first report of plasmid-mediated CMY-2-type AmpC beta-lactamase in S. sonnei. Ampicillin-resistant isolates can develop during the course of antibiotic treatment.