High Rates Of Non-susceptibility Research Articles

High Rates of Nonsusceptibility to Common Oral Antibiotics in Streptococcus pneumoniae Clinical Isolates From the United States (2019-2021).

Streptococcus pneumoniae isolates from the United States (n = 1038; 2019-2021) were susceptible to omadacycline (99.8%), levofloxacin (99.7%), and ceftriaxone (98.1%), whereas doxycycline (80.2%), oral penicillin (63.5%), cefpodoxime (76.8%), and azithromycin (54.4%) activity was limited. Tet(M) did not affect omadacycline activity but altered activity of older tetracyclines including doxycycline, suggesting omadacycline is an important option for treatment of community-acquired bacterial pneumonia.

2139. High Rates of Non-Susceptibility to Common Oral Antibiotics Among Streptococcus pneumoniae Clinical Isolates from the United States (2019-2021)

Abstract Background Major guidelines recommend β-lactams, macrolides, doxycycline (DOX) or respiratory quinolone monotherapy for outpatients with non-severe community-acquired bacterial pneumonia (CABP). Combination therapy is recommended for outpatients with comorbidities. Omadacycline (OMC) was equivalent to moxifloxacin as monotherapy for adults with CABP and was approved for CABP by the US FDA (2018). The activity of OMC and comparators was evaluated against S. pneumoniae (SPN) from the USA, as well as the resistance (R) mechanisms in tetracycline (TET) non-susceptible (NS) SPN. Methods 1,038 SPN from 31 USA centers (2019-2021) were tested by CLSI broth microdilution. Isolates were from CABP (933), bloodstream infection (72), or nosocomial pneumonia (33). A selection of 119 SPN with DOX MIC of 0.25 - >8 mg/L were subjected to genome sequencing for screening of acquired TET-R genes and target site mutations, and serotyping (ST). Results Most SPN isolates were susceptible (S) to OMC (99.8%; FDA), levofloxacin (LEV, 99.7%; CLSI) and tigecycline (TIG; 98.4%; FDA). Other agents had limited activity overall (penicillin 63.5%; or DOX 80.2%; or azithromycin 54.3%) with decreased S against isolates from certain US regions (Table). Only OMC (100% S), LEV (96.8% S) and TIG (96.7% S) were active against TET-NS (MIC, ≥2 mg/L) SPN. Cefpodoxime (70.5% S) and amoxicillin-clavulanate (82.0% S) had suboptimal activity against this R subset and other agent had S ≤36.1%. Isolates from the Pacific region tended to be more S than those from other regions. All TET-NS and 1 TET-S (MIC, 1 mg/L) isolates carried tet(M), and TET-NS had low S to DOX (6.6% S) and azithromycin (3.3% S). TET target site mutations were not observed. SPN belonged to 21 ST; 22F and 35B were the most common among TET-S SPN, whereas 15A, 19A, 09N, and 23A were common among TET-NS SPN. Conclusion Options recommended for the empiric treatment of outpatients with CABP show low S against SPN from the US, except against isolates from the Pacific region. Tet(M) remains the dominant R mechanism, which did not affect OMC activity but significantly altered DOX activity. These data suggest that OMC represents a potential empiric option for treating pneumonia caused by SPN in the USA, including against isolates carrying tet(M). Disclosures Lalitagauri M. Deshpande, PhD, Melinta: Grant/Research Support|Paratek: Grant/Research Support Michael D. Huband, BS, BARDA: This study has been funded in part by BARDA under Contract No. 75A50120C00001.|Entasis: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support Sarah Charbon, MHS, MLS(ASCP)CM, Paratek: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support

Antimicrobial Susceptibility of Neisseria gonorrhoeae in Japan from 2000 to 2015.

Gonococcal infections are difficult to treat because of their multidrug antimicrobial resistance. The outbreak of antimicrobial-resistant Neisseria gonorrhoeae has begun in Asia and particularly in Japan. Therefore, it is very important that we understand the trend of antimicrobial resistance of N. gonorrhoeae in Asia including Japan. Our surveillance of the antimicrobial susceptibility of N. gonorrhoeae began in 2000 under the guidance of the Department of Urology, Gifu University. We report our surveillance data from 2000 to 2015. We collected N. gonorrhoeae strains isolated from patients with gonococcal infections who visited our cooperating medical institutions in Japan from 2000 to 2015. MICs of penicillin G, cefixime, ceftriaxone, tetracycline, spectinomycin, azithromycin, and levofloxacin were determined by the agar dilution method approved by the Clinical and Laboratory Standards Institute. From 2000 to 2015, 2471 isolates of N. gonorrhoeae were collected in Japan. High rates of nonsusceptibility to penicillin, tetracycline, levofloxacin, cefixime, and azithromycin were shown. Around 5% to 10% of the strains isolated had a 0.25-mg/L MIC of ceftriaxone in each year, and 6 strains (0.24%) with a 0.5-mg/L MIC of ceftriaxone were isolated throughout the study period. Approximately 5% to 10% of the strains were resistant to each of ceftriaxone, azithromycin, and levofloxacin according to European Committee on Antimicrobial Susceptibility Testing breakpoints, and the rate has not increased significantly. From this study and previous pharmacodynamic analyses, a single 1-g dose of ceftriaxone is recommended to treat gonorrhea. As strains with high-level ceftriaxone resistance continue to spread, higher doses of ceftriaxone in monotherapy or multiple doses of ceftriaxone should be considered.

Noninvasive pneumococcal clones associated with antimicrobial nonsusceptibility isolated from children in the era of conjugate vaccines.

Carriage and noninvasive pneumococcal isolates frequently have a higher prevalence of antimicrobial nonsusceptibility than invasive isolates. From 2009 to 2014, we determined the associated clones in 169 pediatric noninvasive nonsusceptible pneumococci from a total of 506 isolates collected after 7- and 13-valent conjugate vaccine introduction (PCV7/13) to the Irish childhood immunization schedule in 2008 and 2010, respectively. We compared our results to those from 25 noninvasive pediatric pneumococcal isolates collected in 2007, the year before introduction of conjugate vaccines. In 2007, England(14)-9 and Spain(9V)-3 accounted for 12% and 32% of nonsusceptible clones, respectively, but in 2009 to 2014, their prevalence fell to 0% and 2.4%. Furthermore, there was a significant decline in Spain(6B)-2 and its variants from 2009 to 2014 (P = 0.0024). Fluctuations occurred in clonal complex 320 associated with serotype 19A. The prevalence of Sweden(15A)-25 and its variants and ST558 (a single-locus variant of Utah(35B)-24) associated with nonvaccine serotypes (NVT) 15A and 35B increased from 0% and 8% in 2007 to 19% and 16% in 2013 to 2014, respectively. Pilus locus 1 (PI-1) is associated with the spread of some nonsusceptible pneumococcal clones. PI-1 was more frequently associated with PCV7/13 serotypes than NVT (P = 0.0020). Our data highlight the value of surveillance of noninvasive pneumococci following conjugate vaccine introduction. Importantly, emerging clones associated with NVT may limit the effectiveness of PCV7/13 in reducing the high rate of nonsusceptibility among pediatric noninvasive pneumococci, with implications for empirical treatment strategies.

Molecular epidemiology and analysis on resistant mechanisms of macrolide-nonsusceptible Moraxella catarrhalis

Objective To analyze the molecular epidemiology and resistant mechanisms of macrolide-nonsusceptible Moraxella catarrhalis. Methods A total of 383 strains of Moraxella catarrhalis were collected from nasopharynx of children under 2 years old.The minimum inhibition concentration (MIC) values were determined by Etest method, and the production of β-lactamase was examined by using a nitrocefin-based test.The pulsed-field gel electrophoresis (PFGE) method was used to analyze the type of different isolates.Polymerase chain reaction (PCR) and sequencing were performed for the resistance mechanism of macrolide resistance in Moraxella catarrhalis.The non-susceptibility rates of six cities(Beijing, Shanghai, Jinan, Nanjing, Wuhan and Dongguan) were compared by χ2 test. Results According to Clinical and Laboratory Standards Institute(CLSI) breakpoints, the non-susceptibility rates for erythromycin and azithromycin in 383 strains of Moraxella catarrhalis were 40% and 23%, respectively.Whereas, the non-susceptibility rates were 59% and 60% based on pharmacokinetics/pharmacodynamics (PK/PD) breakpoints.Significant differences in non-susceptibility rates to macrolide were observed in different cities, and the higher non-susceptibility rates were determined in relatively northern cities, such as Beijing and Jinan.Among the 383 strains of Moraxella catarrhalis, 92%(353/383) of isolates produced β-lactamase.A total of 14 patterns of groups were generated by PFGE in 37 high-level macrolide resistant Moraxella catarrhalis, and 43%(16/37) of isolates could be considered to be related or indistinguishable to group A.In this study, the ermA, ermB, mefA, and mefE genes were not detected, while the A2982T, A2796T, A2983T mutations in 23S rRNA gene may be related to macrolide resistance in Moraxella catarrhalis.The A2982T and A2796T mutations conferred high-level macrolide resistance, while the A2983T mutation conferred low-level resistance. Conclusions A large number of macrolide-nonsusceptible Moraxella catarrhalis isolates are detected in the study.The macrolide resistance is probably related to the mutations in 23S rRNA gene, and the relationship between MIC values of macrolide and mutations has been determined.（Chin J Lab Med,2012,35:247-252） Key words: Macrolides; Moraxella(branhamella) catarrhalis; Drug resistance，bacterial; RNA，ribosomal，23S; Mutation

Increasing Trends in Antimicrobial Resistance among Clinically Important Anaerobes and Bacteroides fragilis Isolates Causing Nosocomial Infections: Emerging Resistance to Carbapenems

This study reports data on the susceptibilities to five commonly used antianaerobic agents of five clinically frequently encountered anaerobes from 2000 to 2007 and to Bacteroides fragilis isolates causing nosocomial infections from 1990 to 2006. There was a trend of decreasing susceptibilities of these anaerobes to ampicillin-sulbactam, cefmetazole, chloramphenicol, and clindamycin with time during the study period. The rates of susceptibility to clindamycin and cefmetazole for all clinical isolates of Bacteroides fragilis isolates were higher than those of isolates associated with nosocomial infections. The MICs of 207 anaerobic blood isolates collected in 2006 to 14 antimicrobial agents were determined by the agar dilution method. The rates of nonsusceptibility to imipenem and meropenem were 7% and 12% for B. fragilis isolates (n = 60), 7% and 3% for Bacteroides thetaiotamicron isolates (n = 30), 4% and 4% for Fusobacterium species (n = 27), 6% and 0% for Prevotella species (n = 16), 15% and 0% for Clostridium species (n = 28), and 0% and 0% for Peptostreptococcus species (n = 32). The rates of susceptibility to moxifloxacin were 90% for B. fragilis isolates, 87% for B. thetaiotaomicron isolates, 81% for Fusobacterium species, 75% for Prevotella species, 93% for Clostridium species, and 78% for Peptostreptococcus species. Thirty-six percent of Clostridium species and 12% of Peptostreptococcus species were not susceptible to metronidazole. Comparison of the data with the data from a previous survey from the same institute in 2002 revealed higher rates of nonsusceptibility to carbapenems, especially for B. fragilis, Fusobacterium species, and Prevotella species isolates. The high rates of nonsusceptibility to commonly used antianaerobic agents mandate our attention, and periodic monitoring of the trend of the resistance is crucial.

Invasive Streptococcus pneumoniae in France: antimicrobial resistance, serotype, and molecular epidemiology findings from a monthly national study in 2000 to 2002.

A study of 257 French invasive pneumococci isolated between 2000 and 2002 showed high rates of nonsusceptibility to penicillin and macrolides (50%), contrasting with a low frequency of resistance to amoxicillin or levofloxacin (<1%) and tolerance to vancomycin (0%). The genetic homogeneity of some serogroups, including serogroup 1, enhanced the risk of epidemiological changes.

Multicenter surveillance of antimicrobial resistance of major bacterial pathogens in intensive care units in 2000 in Taiwan.

A susceptibility surveillance study of 1,274 bacterial isolates recovered from various clinical specimens from patients in intensive care units (ICUs) of five major teaching hospitals was carried out from March, 2000, to June, 2000, in Taiwan. This study demonstrated a high rate (66%) of oxacillin resistance in Staphylococcus aureus (ORSA), a high rate of nonsusceptibility to penicillin (intermediate, 50% and highly resistant, 8%), and high rates of cefotaxime nonsusceptibility for S. pneumoniae (intermediate, 29% and resistant, 4%), Enterobacter cloacae (57%), Serratia marcescens (34%), and Citrobacter freundii (60%). High rate of ceftazidime nonsusceptibility for Pseudomonas aeruginosa (22%), and high rates of imipenem nonsusceptibility for P. aeruginosa (15%) and Acinetobacter baumannii (22%) were also found. The percentage (11.9%) of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli was greater than that (11.3%) for Klebsiella pneumoniae. Rates of quinupristin-dalfopristin nonsusceptibility for S. pneumoniae (42%), Enterococcus faecium (71%), and ORSA (39%) were high, but no vancomycin-resistant enterococci were found in this study. The resistance rates of some pathogen varied by institution or type of ICUs. Surveillance for antimicrobial resistance among bacterial pathogens in hospitals, particularly in ICU settings with a preexisting higher resistance burden, is mandatory in establishing and/or modifying guidelines for empirical treatment of severe infections in ICU patients caused by these antimicrobial-resistant pathogens.

Multicenter surveillance of antimicrobial resistance of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in Taiwan during the 1998-1999 respiratory season.

A susceptibility surveillance study of 276 isolates of Streptococcus pneumoniae, 301 of Haemophilus influenzae, and 110 of Moraxella catarrhalis was carried out from November 1998 to May 1999 in Taiwan. High rates of nonsusceptibility to penicillin (76%), extended-spectrum cephalosporins (56%), azithromycin (94%), clarithromycin (95%), and trimethoprim-sulfamethoxazole (TMP-SMX) (65%) for S. pneumoniae isolates and high rates of nonsusceptibility to amoxicillin (58%) and TMP-SMX (52%) for H. influenzae isolates were found. Higher percentages of S. pneumoniae isolates nonsusceptible to aminopenicillins, extended-spectrum cephalosporins, macrolides, and TMP-SMX were observed among penicillin-intermediate and -resistant isolates. All quinolones tested were active in vitro against these three organisms.