High Rates Of Macrolide Resistance Research Articles

Macrolide Resistance in the Aerococcus urinae Complex: Implications for Integrative and Conjugative Elements.

The recognition of the Aerococcus urinae complex (AUC) as an emerging uropathogen has led to growing concerns due to a limited understanding of its disease spectrum and antibiotic resistance profiles. Here, we investigated the prevalence of macrolide resistance within urinary AUC isolates, shedding light on potential genetic mechanisms. Phenotypic testing revealed a high rate of macrolide resistance: 45%, among a total of 189 urinary AUC isolates. Genomic analysis identified integrative and conjugative elements (ICEs) as carriers of the macrolide resistance gene ermA, suggesting horizontal gene transfer as a mechanism of resistance. Furthermore, comparison with publicly available genomes of related pathogens revealed high ICE sequence homogeneity, highlighting the potential for cross-species dissemination of resistance determinants. Understanding mechanisms of resistance is crucial for developing effective surveillance strategies and improving antibiotic use. Furthermore, the findings underscore the importance of considering the broader ecological context of resistance dissemination, emphasizing the need for community-level surveillance to combat the spread of antibiotic resistance within the urinary microbiome.

Influence of COVID-19 pandemic on the epidemiology of Mycoplasma pneumoniae infections among hospitalized children in Henan, China

BackgroundIncreasing reports have indicated that non-pharmaceutical interventions to control the COVID-19 pandemic may also have an effect on the prevalence of other pathogens. Mycoplasma pneumoniae is an important atypical pathogen prevalent in children with high rates of macrolide resistance. The aim of this study was to investigate the epidemiological characteristics of M. pneumoniae infection in children before and during the COVID-19 pandemic. MethodsIn this study, M. pneumoniae detection results were extracted from Henan Children's Hospital from 2018 to 2021. The epidemiological characteristics of pediatric M. pneumoniae infection were analyzed. ResultsWe found that the highest positive rate of M. pneumoniae infection was 11.00 % in 2018, 14.01 % in 2019, followed by 11.24 % in 2021 and 8.75 % in 2020 (p < 0.001). Most tested children had respiratory system manifestations, and pneumoniae was the most common diagnosis (53.23 %). An increase in the number of positive cases was observed with an increase in age, with a higher number of cases among children over 6 years old. No positive cases were identified among children aged 1–28 days. The decrease in the positive rate among children aged between1–6 years old in 2020 and 2021 was found to be statistically significant (p < 0.001). The pre-pandemic period demonstrated a higher incidence rate in the fall, whereas the summers and winters exhibited a significantly higher positive rate during the pandemic period (p < 0.001). Different regions in Henan also showed different epidemic patterns. ConclusionsIn summary, strict pandemic measures influenced the spread of M. pneumoniae to some extent and changed demographic characteristics, including age, season and regional distribution. Continuous monitoring is required for the control and prevention of related diseases.

Infective anoproctitis in men having sex with men: Don’t forget Mycoplasma genitalium

ObjectivesThe aim was to describe the clinical characteristics of symptomatic anoproctitis and the occurrence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG) infections in a prospective cohort of MSM patients. MethodsFrom February 2018 to January 2020, all consecutive patients presenting at the Leopold Bellan Proctology Institute of Saint-Joseph Hospital, Paris, France with symptoms of anoproctitis were tested on rectal samples for C. trachomatis (CT), N. gonorrhoeae (NG), M. genitalium (MG). Clinical, microbiological, biological data, STI risk factors, medical history and treatments were collected. ResultsThree hundred and sixty-five patients were included for suspected infective anoproctitis. CT was detected in 84/365 (23%) patients, NG in 45/365 (12%) and MG in 46/315 patients (15%), associated with macrolide resistance in 28/46 MG strains (61%). The most frequent symptoms were rectal pains, rectal bleeding, purulent discharge in 253 (79%), 191 (60%), and 164 (51%) of cases respectively. In comparison with MG infections, ulcerations, erythematous proctitis, rectorragia and false needs were more frequently described in CT infections, while purulent proctitis, functional pain and purulent discharge were more often observed in NG and CT anoproctitis. ConclusionWe found a high prevalence rate of STIs due to CT, NG, while MG detection was associated with a high rate of macrolide resistance in a cohort of MSM patients. Our results confirm that in cases of symptomatic anoproctitis, MG should be tested in association with other STI pathogens.

The epidemiology, clinical characteristics, and macrolide susceptibility of Mycoplasma pneumoniae pneumonia in children in Southern Taiwan, 2019-2020.

Since the global use of the pneumococcal conjugate vaccine, Mycoplasma pneumoniae (MP) has become the most common bacterial cause of lower respiratory tract infections among children. Monitoring the changing epidemiology and antimicrobial resistance rates of this organism is important for MP clinical management. This study characterizes key features of MP during the 2019-2020 epidemic in children in Taiwan. The cohort included all hospitalized children under 18 years of age with polymerase chain reaction (PCR)-confirmed community-acquired mycoplasma pneumonia (CAMP) in southern Taiwan. Macrolide resistance was identified by mutations in domain V of MP 23S rRNA. Severe disease referred to symptoms warranting oxygen therapy, septic shock, or intensive care unit admission. Among 495 LRTI patients, 195 (39.4%) had CAMP, of which 106 (54.4%) had concurrent serological evidence of MP infection. The diagnostic sensitivity of IgM in the acute phase was 65.6%. CAMP case numbers were highest from July 2019 to January 2020. The most common clinical presentations of CAMP were fever (99.0%), cough (99.0%), and coryza (31.8%). Despite a high rate of macrolide resistance (88.1%), macrolide-resistant MP (MRMP) did not differ from macrolide-sensitive MP (MSMP) in clinical course or severity. Delayed administration of effective antimicrobial treatment was also associated with severe disease (p<0.05). Early diagnosis and determination of MRMP are needed for effective management of MP infection.

Increased Macrolide Resistance Rate of M3562 Mycoplasma pneumoniae Correlated With Macrolide Usage and Genotype Shifting.

To characterize Mycoplasma pneumoniae (MP) strains and to clarify the continuous high rates of macrolide resistance, 1,524 oropharyngeal swabs collected from children in Beijing Children’s Hospital infected with MP during 2016-2019 were analyzed. Among the 1,524 samples, 1,386 harbored mutations associated with macrolide resistance; 1,049 samples were successfully classified into 11 genotypes using multiple locus variable-number tandem-repeat analysis (MLVA). The proportion of the predominant type, M4572, decreased from 84.49 to 70.77% over the time period examined, while that of M3562 increased from 11.63 to 24.67%. Notably, we also found that the frequency of macrolide resistance in M3562 drastically increased, from 60% in 2016 to 93.48% in 2019. Clinical data suggested that the frequency of resistant M3562 was higher in the macrolide usage group than in the nondrug usage group (90.73 vs 53.57%, P<0.0001), while the resistance rate of M4572 was not substantially affected by previous macrolide exposure. These findings validated that antimicrobial application and clonal expansion of resistant MP strains play important roles in the high rates of macrolide resistance.

1631. Mycobacterium septicum: A 6-year Clinical Experience from a Tertiary Hospital and Reference Laboratory

Background Mycobacterium septicum is a rapidly growing non-tuberculous mycobacterium. It is a ubiquitous organism capable of causing infections in both healthy and immunocompromised individuals. Only a few cases have been reported to date, and standard therapeutic regimens, and optimal treatment duration have not been defined.MethodsWe conducted a retrospective chart review of all patients seen at Mayo Clinic in Rochester, MN from July 2014 to March 2020 from whom Mycobacterium septicum was isolated in culture by our clinical microbiology laboratory.ResultsThere were 12 patients identified with M. septicum infection – 7 males and 5 females. The average age was 67 years, with an age range of 48 to 80 years. Seven of 12 isolates obtained were from sputum samples. Only one patient was on immunosuppressive medication. Three cases were considered clinically significant infections for which directed anti-mycobacterial therapy was instituted. In two of these three cases, co-infection with Mycobacterium avium complex (MAC) was seen. Underlying structural lung disease was present in the two cases of pulmonary infections. Peritoneal dialysis catheter-related peritonitis was seen in the third case. All the isolates were susceptible to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole (TMP-SMX). The isolates were resistant to clarithromycin and doxycycline.Patient Characteristics, Associated M. septicum Illness, and Therapy Provided Antimicrobial Susceptibility Profiles of the Mycobacterium septicum Isolates, MIC (mcg/mL) and Interpretation Patient Demographics and Specimen Source of Mycobacerium septicum Isolates ConclusionM. septicum is an unusual cause of non-tuberculous mycobacterial infection. The presence of a foreign body may increase the risk of infection. Individuals with underlying structural lung disease are also likely to be at increased risk of developing pulmonary infection. Generalized treatment recommendations are limited by the lack of prospective controlled trials; hence, optimal antibiotic regimen and treatment duration have not been firmly established. Susceptibility testing should be performed to guide treatment selection, but the use of combination therapy with potentially empiric agents like amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and TMP-SMX as demonstrated in this small study, can be considered. A high rate of macrolide resistance was noted in our study.Disclosures All Authors: No reported disclosures

Molecular characterization of Streptococcus pneumoniae isolated from pediatric patients in Shanghai, China.

Streptococcus pneumoniae is a major cause of bacterial infection among infants and young children with high morbidity and mortality. The serotype distribution of S. pneumoniae varies with geography, time, age, and disease. We aimed to investigate the current status of molecular characteristics of S. pneumoniae strains isolated from pediatric patients in Shanghai, China. Between 2016 and 2018, 73 clinical S. pneumoniae isolates were characterized by capsular serotype, multilocus sequence typing, antibiotic susceptibility, and resistant genes. The most common serotypes were 19F (39.7%), 19A (16.4%), 6A (11.0%), 14 (9.6%), and 6B (8.2%). The coverage rates of the 7-, 10- and 13-valent pneumococcal conjugate vaccines were 64.4%, 64.4%, and 91.8%, respectively. The five predominant sequence types were ST271 (37.0%), ST320 (19.2%), ST3173 (11.0%), ST876 (6.8%), and ST81 (4.1%), which were mainly associated with serotypes 19F, 19A, 6A, 14, and 23F, respectively. The rates of resistance to penicillin and ceftriaxone were 21.9% and 39.7%, respectively. All strains displayed resistance to macrolides, 54.8% of which possessed both erm(B) and mef(A/E) genes, and 41.1% carried the erm(B) gene alone. Tn2010 (41.1%) was the most common transposon. Clonal complex 271 (Taiwan19F-14 clone) played a dominant role in the dissemination of pneumococcal isolates. The prevalent serotypes indicated a lack of the 7-valent pneumococcal conjugate vaccine, which has not been included in national immunization programs in mainland China. The high rate of macrolide resistance made the empirical use of macrolides alone not suitable for treating pediatric pneumococcal disease.

High rates of treatment failure for Mycoplasma genitalium among men and women attending a sexual health clinic

BackgroundMycoplasma genitalium (Mgen) causes non-gonococcal urethritis (NGU) and is believed to cause pelvic inflammatory disease (PID). High rates of macrolide resistance are well documented globally for Mgen. In Brighton, patients...

High prevalence of Mycoplasma genitalium infection and macrolide resistance in patients enrolled in HIV pre-exposure prophylaxis program

ObjectivesLimited data on Mycoplasma genitalium infection has been reported among PrEP users. The aim of this study was to estimate the prevalence and macrolide resistance of M. genitalium infection among enrollees in a French PrEP program. Patients and methodsM. genitalium infection screening was systematically and prospectively proposed to patients of the Bordeaux PrEP program (between January 2016 and February 2017). Macrolide resistance was evaluated in M. genitalium-positive patients. ResultsAmong 89 clients, M. genitalium infection prevalence was 10% (mainly asymptomatic) with a high rate of macrolide resistance (58%). ConclusionsBecause of a high level of macrolide resistance, a systematic search for M. genitalium macrolide resistance associated-mutations may be recommended in PrEP users before initiating the antibiotic therapy.

Mycoplasma genitalium: high prevalence of resistance to macrolides and frequent anorectal infection in men who have sex with men in western Sydney

ObjectivesWe aimed to estimate the prevalence of Mycoplasma genitalium infection and of mutations linked to macrolide resistance using the ResistancePlus MG assay (SpeeDx, Sydney, New South Wales, Australia) in first-void...

Macrolide and lincosamide resistance in staphylococcal clinical isolates in Nablus, Palestine

Macrolide and lincosamide antibiotics are used for the treatment of staphylococcal infections, especially for penicillin-allergic patients. In the present study, we evaluate the prevalence of resistance to macrolide and lincosamide antibiotics among staphylococci isolates. A total of 200 staphylococcal clinical isolates were collected from January 2012 to April 2013. Minimal inhibitory concentrations of erythromycin and clindamycin were determined by agar dilution method. An erythromycin-clindamycin induction test was performed for isolates that were only resistant to erythromycin. Representative erythromycin-resistant isolates were examined for erythromycin resistance genes using PCR. Among staphylococci isolates, resistance frequencies of erythromycin and clindamycin were 65.5% and 20.5%, respectively. Erythromycin resistance was found to be mediated by putative efflux (50.4%) and target site modification (49.6%). Inducible target site modification resistance was detected in 19.1% of erythromycin-resistant isolates. Among the examined 36 staphylococci isolates, msr(A), erm(C), erm(A), and mef(A/E) genes were detected in 55.6%, 30.6%, 25%, and 0%, respectively. Results of the current study indicate the presence of high rates of macrolide resistance and inducible phenotypes among staphylococcal isolates. It is also essential to keep in mind variations of resistance rates among various age groups and specimen types.

Genetic determinants and elements associated with antibiotic resistance in viridans group streptococci

To investigate the distribution of erythromycin, tetracycline and chloramphenicol resistance mechanisms and determinants and the relevant genetic environments and elements in viridans group streptococci (VGS). A total of 263 VGS collected from routine throat swabs in 2010-12 and identified to the species level were studied. Antibiotic resistance determinants and the relevant genetic contexts and elements were determined using amplification and sequencing assays and restriction analysis. The investigation provided original information on the distribution of resistance mechanisms, determinants and genetic elements in VGS. Erythromycin-resistant isolates totalled 148 (56.3%; 37 belonging to the cMLS phenotype and 111 belonging to the M phenotype); there were 72 (27.4%) and 7 (2.7%) tetracycline- and chloramphenicol-resistant isolates, respectively. A number of variants of known genetic contexts and elements carrying determinants of resistance to these antibiotics were detected, including the mega element, Φ10394.4, Tn2009, Tn2010, the IQ element, Tn917, Tn3872, Tn6002, Tn916, Tn5801, a tet(O) fragment from ICE2096-RD.2 and ICESp23FST81. These findings shed new light on the distribution of antibiotic resistance mechanisms and determinants and their genetic environments in VGS, for which very few such data are currently available. The high frequency and broad variety of such elements supports the notion that VGS may be important reservoirs of resistance genes for the more pathogenic streptococci. The high rates of macrolide resistance confirm the persistence of a marked prevalence of resistant VGS in Europe, where macrolide resistance is, conversely, declining among the major streptococcal pathogens.

Molecular investigation of antibiotic resistance genes in methicillin resistant Staphylococcus aureus isolated from nasal cavity in pediatric service

Methicillin-resistant staphylococci may also be resistant to some other antibiotics as well as β-lactams. Co-existence of resistance to methicillin and macrolides was genetically investigated in Staphylococcus aureus. A total of 59 S. aureus strains isolated from nasal cavity of patients hospitalized in the pediatric service were investigated for their susceptibility to oxacillin and erythromycin. In addition, the β-lactams resistance gene (mecA and blaZ), the erythromycin resistance methylase genes (ermA, ermB, and ermC) and macrolide efflux genes msrA were analysed by multiplex PCR. The minimal inhibitory concentration (MIC) values revealed that 98 and 97% of isolates were resistant to oxacillin and erythromycin, respectively. In addition, the frequency of resistant strains for tested genes was 66% (mecA), 100% (blaZ), 15% (ermA), 30% (ermB), 22% (ermC) and 36% (msrA). A high rate of macrolide resistance was determined in methicillin-resistant staphylococci. The erm gene was the most frequently detected. Results of susceptibility testing and the carriage of resistance genes did not match. Thus, polymerase chain reaction (PCR) multiplex identification of antibiotic resistance genes, as a rapid and accurate technique, could be a supplementary method, which can be easily incorporated into the diagnostic molecular microbiology laboratory work flow. Key words: Staphylococcus aureus, multidrug resistance, multiplex polymerase chain reaction (PCR).

Molecular epidemiology, antimicrobial susceptibilities and resistance mechanisms of Streptococcus pyogenes isolates resistant to erythromycin and tetracycline in Spain (1994–2006)

BackgroundGroup A Streptococcus (GAS) causes human diseases ranging in severity from uncomplicated pharyngitis to life-threatening necrotizing fasciitis and shows high rates of macrolide resistance in several countries. Our goal is to identify antimicrobial resistance in Spanish GAS isolates collected between 1994 and 2006 and to determine the molecular epidemiology (emm/T typing and PFGE) and resistance mechanisms of those resistant to erythromycin and tetracycline.ResultsTwo hundred ninety-five out of 898 isolates (32.8%) were erythromycin resistant, with the predominance of emm4T4, emm75T25, and emm28T28, accounting the 67.1% of the 21 emm/T types. Spread of emm4T4, emm75T25 and emm28T28 resistant clones caused high rates of macrolide resistance. The distribution of the phenotypes was M (76.9%), cMLSB (20.3%), iMLSB (2.7%) with the involvement of the erythromycin resistance genes mef(A) (89.5%), msr(D) (81.7%), erm(B) (37.3%) and erm(A) (35.9%).Sixty-one isolates were tetracycline resistant, with the main representation of the emm77T28 among 20 emm/T types. To note, the combination of tet(M) and tet(O) tetracycline resistance genes were similar to tet(M) alone reaching values close to 40%. Resistance to both antibiotics was detected in 19 isolates of 7 emm/T types, being emm11T11 and the cMLSB phenotype the most frequent ones. erm(B) and tet(M) were present in almost all the strains, while erm(A), mef(A), msr(D) and tet(O) appeared in less than half of them.ConclusionsSpanish GAS were highly resistant to macrolides meanwhile showed minor resistance rate to tetracycline. A remarkable correlation between antimicrobial resistance and emm/T type was noticed. Clonal spread of emm4T4, emm75T25 and emm28T28 was the main responsable for macrolide resistance where as that emm77T28 clones were it to tetraclycline resistance. A wide variety of macrolide resistance genes were responsible for three macrolide resistance phenotypes.

Nonbismuth Quadruple (Concomitant) Therapy: Empirical and Tailored Efficacy versus Standard Triple Therapy for Clarithromycin‐Susceptible Helicobacter pylori and versus Sequential Therapy for Clarithromycin‐Resistant Strains

Using quadruple clarithromycin-containing regimens for Helicobacter pylori eradication is controversial with high rates of macrolide resistance. To evaluate antibiotic resistance rates and the efficacy of empirical and tailored nonbismuth quadruple (concomitant) therapy in a setting with cure rates <80% for triple and sequential therapies. 209 consecutive naive H. pylori-positive patients without susceptibility testing were empirically treated with 10-day concomitant therapy (proton pump inhibitors (PPI), amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg; all drugs b.i.d.). Simultaneously, 89 patients with positive H. pylori culture were randomized to receive triple versus concomitant therapy for clarithromycin-susceptible H. pylori, and sequential versus concomitant therapy for clarithromycin-resistant strains. Eradication was confirmed with ¹³C-urea breath test or histology 8 weeks after completion of treatment. Per-protocol (PP) and intention-to-treat eradication rates after empirical concomitant therapy without susceptibility testing were 89% (95%CI:84-93%) and 87% (83-92%). Antibiotic resistance rates were: clarithromycin, 20%; metronidazole, 34%; and both clarithromycin and metronidazole, 10%. Regarding clarithromycin-susceptible H. pylori, concomitant therapy was significantly better than triple therapy by per protocol [92% (82-100%) vs 74% (58-91%), p = 0.05] and by intention to treat [92% (82-100%) vs 70% (57-90%), p = 0.02]. As for antibiotic-resistant strains, eradication rates for concomitant and sequential therapies were 100% (5/5) vs 75% (3/4), for clarithromycin-resistant/metronidazole-susceptible strains and 75% (3/4) vs 60% (3/5) for dual-resistant strains. Empirical 10-day concomitant therapy achieves good eradication rates, close to 90%, in settings with multiresistant H. pylori strains. Tailored concomitant therapy is significantly superior to triple therapy for clarithromycin-susceptible H. pylori and at least as effective as sequential therapy for resistant strains.

High macrolide resistance inStreptococcus pyogenesstrains isolated from children with pharyngitis in China

To assess the macrolide resistance, phenotype, and genotypic characterization of Streptococcus pyogenes isolated from Chinese children with pharyngitis. Minimal inhibitory concentration (MIC) with nine antibiotics was determined on 188 isolates of S. pyogenes collected from outpatients with pharyngitis in four children's hospitals in different regions of China in 2007. MICs of penicillin, chloramphenicol, cefradine, levofloxacin, macrolide (erythromycin, clarithromycin, azithromycin,), clindamycin, and tetracycline were determined by the microdilution method. The macrolide resistant phenotypes of isolates were determined through a double-disk. The macrolide-resistant genes (mefA, ermB, and ermA) were amplified by polymerase chain reaction (PCR). Over 95% were resistant to macrolides, while 92.0% were resistant to tetracycline. We also found that all isolates were sensitive to penicillin, chloramphenicol, cefradine, and levofloxacin. Among the 173 erythromycin resistant strains, 171 (98.8%) were assigned to the cMLS phenotype, while the remaining 2 (1.2%) were assigned to the iMLS phenotype. Among the 171 cMLS isolates, 168 isolates (98.2%) had the ermB gene accounting for 98.2%. Meanwhile, 2 iMLS isolates had the ermA gene. Macrolides were highly resistant to ermB positive strains (MIC(90) > 256 microg/ml). Neither the M-phenotype nor the mefA gene was detected. Meanwhile, our studies of multiple centers showed that consumption of macrolides from 2000 to 2006 was very high. The main phenotype is cMLS, and the ermB gene code is the main resistance mechanism against macrolides in S. pyogenes. The high rate of macrolide resistance to S. pyogenes was observed, which may be correlated with the overuse of these antibiotics in China.

A Case Series of Macrolide Treatment Failures in Community Acquired Pneumonia

This was a retrospective, multi-center study of patients admitted to hospital with community-acquired pneumonia, caused by Streptococcus pneumoniae after failing to respond to >2 days of outpatient macrolide therapy. 122 cases, treated between 2000-2004, were enrolled from 31 North American sites between January 2004 - March 2005. Non-susceptible isolates (predominately low-level resistance: erythromycin MICs of 1-16 mcg/ml) were recovered from 87 patients (71%). Bacteremia was present in 63 patients (52%). The in-hospital mortality rate was 5.7 %; all 7 patients who died were bacteremic, 6 had a non-susceptible isolate. We report here the largest series of macrolide failures published to date. The patients were notable for their high rates of macrolide resistance, bacteremia, and mortality. High-level macrolide resistance remains rare among US patients failing outpatient macrolides. The majority of cases and virtually all of the mortality occurred in patients with low-level resistant strains.

Multicentre surveillance of the prevalence and molecular epidemiology of macrolide resistance among pharyngeal isolates of group A streptococci in the USA

Rates of macrolide resistance in group A streptococci (GAS) were reported to be low in the US in the 1990s. However, we documented an unexpectedly high rate of macrolide resistance among GAS in Pittsburgh, PA, in 2001 and 2002. In an effort to define the current prevalence of macrolide-resistant GAS in the US, a multicentre surveillance project was initiated. Between October 2002 and May 2003, 50 pharyngeal GAS isolates per month were requested from each of the nine participating sites representing a wide geographical distribution. Standard susceptibility testing was performed and the macrolide resistance phenotype was assessed using double-disc diffusion testing. Monthly and annual rates of macrolide resistance were calculated for each site. An adjusted overall rate of macrolide resistance was determined to account for differences in the numbers of GAS isolates sent from each centre. Overall, 171 of the 2797 collected isolates of GAS (6.1%) were resistant to erythromycin. The adjusted overall resistance rate was 5.2%. Rates of macrolide resistance varied by site (range 3.0-8.7%) and also by month (<2% to >10%). The M phenotype of macrolide resistance accounted for >60% of all macrolide-resistant isolates recovered in this study. These data suggest an increasing prevalence and broad geographical distribution of macrolide-resistant GAS in the US, indicating the need for ongoing local and national longitudinal surveillance to define the extent of this problem.

Telithromycin and quinupristin-dalfopristin resistance in clinical isolates of Streptococcus pyogenes: SMART Program 2001 Data.

This study evaluated the current status of antimicrobial resistance in clinical isolates of Streptococcus pyogenes in Taiwan as part of the SMART (Surveillance from Multicenter Antimicrobial Resistance in Taiwan) program. In 2001, 419 different isolates of S. pyogenes, including 275 from respiratory secretions, 87 from wound pus, and 31 from blood, were collected from nine hospitals in different parts of Taiwan. MICs of 23 antimicrobial agents were determined at a central location by the agar dilution method. All of the isolates were susceptible to penicillin (MIC at which 90% of the isolates were inhibited [MIC(90)], <or=0.03 microg/ml), cefotaxime (MIC(90), <or=0.03 microg/ml), cefepime (MIC(90), 0.06 microg/ml), meropenem (MIC(90), <or=0.03 microg/ml), moxifloxacin (MIC(90), 0.25 microg/ml), vancomycin (MIC(90), 0.5 microg/ml), and linezolid (MIC(90), 1 micro g/ml). Overall, 78% of isolates were not susceptible to erythromycin (54% were intermediate, and 24% were resistant), and 5% were not susceptible to clindamycin. Of the 101 erythromycin-resistant isolates, 80.2% exhibited the M phenotype (mefA gene positive), 18.9% exhibited the cMLS (constitutive resistance to macrolides-lincosamides-streptogramin B [MLS]) phenotype (ermB gene positive), and 1% exhibited the iMLS (inducible resistance to MLS) phenotype (ermB gene positive). Fluoroquinolones (sitafloxacin > moxifloxacin > ciprofloxacin = levofloxacin = gatifloxacin > gemifloxacin) demonstrated potent activity against nearly all of the isolates of S. pyogenes tested. Thirty-two isolates (8%) were not susceptible to quinupristin-dalfopristin. Seventeen percent of isolates had telithromycin MICs of >or=1 microg/ml, and all of these isolates exhibited erythromycin MICs of >or=32 microg/ml. The high prevalence of resistance to telithromycin (which is not available in Taiwan) limits its potential use in the treatment of S. pyogenes infections, particularly in areas with high rates of macrolide resistance.

High rate of macrolide resistance in Staphylococcus aureus strains from patients with cystic fibrosis reveals high proportions of hypermutable strains.

Incidence of resistance to erythromycin at our institution reached 53% in 122 Staphylococcus aureus isolates obtained from patients with cystic fibrosis (CF) from 1997 to 1999. Macrolide-resistance genes were sought for in 20 erythromycin-resistant isolates from 9 patients with CF by use of polymerase chain reaction; 13 strains did not contain any known macrolide-resistance genes. Sequence of ribosomal genes rrl (23S rRNA), rplD (L4 protein), and rplV (L22 protein) revealed the presence of mutations in the target site of macrolides in 15 of the 20 isolates. A higher proportion of hypermutator strains was observed in a group of 89 CF staphylococcal isolates, compared with that in the 74 non-CF control isolates (13/89 vs. 1/74 with resistance to rifampin [P=.0045]; 9/89 vs. 1/74 with resistance to streptomycin [P=.04]). Various mutations or deletions of the mutator mutS gene were found not only in 5 of 11 hypermutable strains but also in 3 nonhypermutable strains harboring a large number of ribosomal mutations. The presence of a high proportion of hypermutable strains might explain the adaptation of certain strains in the patients, as well as the emergence of macrolide resistance as a result of antibiotic selective pressure in CF.