Penicillin-nonsusceptible S. Pneumoniae Research Articles

Serotype Distribution, Antimicrobial Susceptibility, and Multilocus Sequencing Type (MLST) of Streptococcus pneumoniae From Adults of Three Hospitals in Shanghai, China.

Background: Streptococcus pneumoniae, a main causative agent associated with invasive and non-invasive infection in elderly population, is a major global health problem. After pneumococcal conjugate vaccines (PCV) and pneumococcal polysaccharide vaccines (PPV) were introduced, the distribution of S. pneumoniae serotypes has changed. There was currently limited data on epidemiology and status of antimicrobial resistance of S. pneumoniae in Shanghai.Objective: To determine the serotype distribution, antimicrobial susceptibility and molecular epidemiology of S. pneumoniae isolated from adults in Shanghai.Method: A total of 75 S. pneumoniae isolates consecutively collected from 2015 through 2017 were serotyped by conventional multiplex-PCR. The antimicrobial susceptibility was determined by broth microdilution method. The multilocus sequence type (MLST) was performed to estimate the molecular epidemiology.Results: The predominant serotypes among the isolates were 19F (20.00%), 3 (16.00%), 23F (9.33%), 14 (8.00%), and19A (5.33%). The prevalence of pneumococcal strains with serotypes targeted by vaccines PCV7, PCV10, PCV13, and PPV23 was 44, 45.33, 66.67, and 80%, respectively. Penicillin non-susceptible S. pneumoniae (PNSSP) accounted for 16% of the isolates examined and resistance to erythromycin, azithromycin, tetracycline, clindamycin, cefaclor and trimethoprim-sulfamethoxazole were found in 92.00, 90.67, 86.67, 81.33, 54.67, and 54.67% of isolates, with most isolates (78.67%) presenting multidrug-resistance. The top three sequence types (STs) were ST271 (17.33%), ST180 (9.33%), and ST81 (8.00%). The international resistance clone complexes Spain23F-1 (n = 4), Netherland3-31 (n = 8), and Taiwan19F-14 (n = 14) were identified.Conclusions: The S. pneumoniae isolates showed high genetic diversity in Shanghai and the prevalence of antimicrobial resistance was also high among S. pneumoniae isolates, most of which were multidrug-resistant. The spread of international resistance clones might contribute to the increase of resistant isolates. The PPV23 could protect against most pneumococcal capsular serotypes causing infection of adults in Shanghai.

High Rate of Serotype Switching and Genetic Variations Indicates Widespread Recombination Between Clinical and Commensal Penicillin-Nonsusceptible Streptococcus pneumoniae in Tehran.

A total of 161 Streptococcus pneumoniae were collected between 2013 and 2015 in Tehran, Iran. The strains were tested for antimicrobial susceptibility and minimum inhibitory concentrations, serotyped, and genotyped by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Penicillin-binding proteins (PBPs) were also typed by restriction fragment length polymorphism (PBP-RFLP). Out of 161 strains, 32 isolates (20%) were highly resistant to penicillin. The most frequent serotypes among the penicillin-nonsusceptible S. pneumoniae (PNSP) were 14 (24%), 23F (18%), and 19F (17%). RFLP of pbp2b, pbp2x, and pbp1a genes revealed 8, 6, and 7 different patterns, respectively. Analysis of 93 PNSP isolates displayed 80 PFGE types with 8 common types constituting 21 (23%) isolates. The remaining 72 isolates (77%) were single types. MLST indicated a high degree of genetic diversity among the 93 PNSP with 36 different sequence types. Six internationally known penicillin resistant clones were identified in our isolates among which Spain23F-1 (ST81), Spain6B-2 (ST90), and Spain9V-3 (ST156) were the predominant clones. The results indicated international identifiable clones of S. pneumoniae, especially Spain23F-1 with high penicillin resistance could play a major role in spread of antimicrobial resistance in Iran. The extensive sequence variation in PBP2x, PBP2b, and PBP1a in resistant strains of clinical and commensal S. pneumoniae was suggestive of a widespread homologous recombination within S. pneumoniae populations.

Molecular characterization of penicillin non-susceptible Streptococcus pneumoniae isolated before and after pneumococcal conjugate vaccine implementation in Casablanca, Morocco

BackgroundStreptococcus pneumoniae is a major cause of morbidity and mortality worldwide, especially among children and the elderly. The ability to effectively treat pneumococcal infection has been compromised due to the acquisition of antibiotic resistance, particularly to β-lactam drugs. This study aimed to describe the prevalence and molecular evolution of penicillin non-susceptible S. pneumoniae (PNSP) isolated from invasive diseases before and after pneumococcal conjugate vaccine implementation in Casablanca, Morocco.MethodsIsolates were obtained from the Microbiology Laboratory of Ibn Rochd University Hospital Centre of Casablanca. Serogrouping was done by Pneumotest Kit and serotyping by the Quellung capsular swelling. Antibiotic susceptibility pattern was determined by disk diffusion and E-test methods. The PNSP were analyzed by pulsed-field gel electrophoresis (PFGE) and by genotyping of pbp1a, pbp2b, and pbp2x genes.ResultsA total of 361 S. pneumoniae isolates were collected from 2007 to 2014. Of these isolates, 58.7% were obtained before vaccination (2007–2010) and 41.3% after vaccination (2011–2014). Of the 361 isolates, 80 were PNSP (22.2%). Generally, the proportion of PNSP between pre- and post-vaccination periods were 31 and 13% (p = 0.009), respectively. The proportion of PNSP isolated from pediatric and adult (age > 14 years) patients decreased from 34.5 to 22.9% (p = 0.1) and from 17.7 to 10.2% (p = 0.1) before and after vaccine implementation, respectively. The leading serotypes of PNSP were 14 (33 vs. 57%) and 19A (18 vs. 14%) before and after vaccination among children. For adults, serotypes 19A (53%) and 23F (24%) were the dominant serotypes in the pre-vaccination period, while serotype 14 (22%) was the most prevalent after vaccination. There were 21 pbp genotypes in the pre-vaccination period vs. 12 for post-vaccination period. PFGE clustering showed six clusters of PNSP grouped into three clusters specific to pre-vaccination period (clusters I, II and III), two clusters specific to post-period (clusters V and VI) and a cluster (IV) that contained clones belonging to the two periods of vaccination.ConclusionOur observations demonstrate a high degree of genetic diversity among PNSP. Genetic clustering among PNSP strains showed that they spread mainly by a restricted number of PNSP clones with vaccine serotypes. PFGE clustering combined with pbp genotyping revealed that vaccination can change the population structure of PNSP.

Molecular characteristics of penicillin-binding protein 2b, 2x and 1a sequences in Streptococcus pneumoniae isolates causing invasive diseases among children in Northeast China.

Streptococcus pneumoniae is one of the common pathogens causing severe invasive infections in children. This study aimed to investigate the serotype distribution and variations of penicillin-binding proteins (PBPs) 2b, 2x and 1a in S. pneumoniae isolates causing invasive diseases in Northeast China. A total of 256 strains were isolated from children with invasive pneumococcal disease (IPD) from January 2000 to October 2014. All strains were serotyped and determined for antibiotic resistance. The amplicons of penicillin-binding domains in pbp1a, pbp2b and pbp2x genes were sequenced for variation identification. The most prevalent serotypes of isolates in IPD children were 19A, 14, 19F, 23F and 6B. 19A and 19F were the most frequent serotypes of penicillin-resistant S. pneumoniae (PRSP), which present with high resistance to amoxicillin, cefotaxime, ceftriaxone and meropenem. The numbers of amino acid substitutions of penicillin-non-susceptible S. pneumoniae (PNSP) isolates were higher than those of penicillin-sensitive S. pneumoniae isolates in all the PBP genes (p < 0.01). The patterns of amino acid mutation in PBP2b, PBP2x and PBP1a were unique and different from those of other countries. All of the serotype 19A and 19F PRSP isolates carried 25 amino acid mutations, including Ala618 → Gly between positions 560 and 675 in PBP2b and Thr338 → Ala substitutions in PBP2x. The amino acid alterations in PBP2b, PBP2x and PBP1a from S. pneumoniae were closely associated with resistance to β-lactam antibiotics. This study provides new data for further monitoring of genetic changes related to the emergence and spread of resistance to β-lactam antibiotics in China.

Serotype distribution and antimicrobial resistance of invasive Streptococcus pneumoniae isolates from children in Zahedan, Iran

Streptococcus pneumoniae is the leading cause of death among children worldwide. This study was conducted to evaluate the antibiotic resistance patterns and seroepidemiology of invasive S. pneumoniae isolates in children of Zahedan. Invasive isolates of S. pneumoniaewere obtained from normal sterile sites (blood, cerebrospinal fluid, pleural fluid, joint aspirate, peritoneal fluid and pericardial fluid) of pediatric patients (aged ≤14 years) from 3 large hospitals in Zahedan, Iran. The serotyping was carried out by latex agglutination test and the minimum inhibitory concentrations (MIC) of penicillin, as well as other commonly used antibiotics were determined by broth dilution method. During February 2008 to November 2010, a total of 1265 children with suspected invasive bacterial disease were recruited, of whom 75 (5.9%) were identified to have S. pneumoniae as the causative agent of invasive disease. The leading serotypes were 23F, 6B, 3, 19F and 14 (70.7% of all isolates). Intermediate- and high-level resistance, were observed in 37.3 and 45.4% of isolates respectively. Resistance was also demonstrated against erythromycin (90.7%), cotrimoxazole (80.0%), tetracycline (66.6%), cefuroxime (62.7%), imipenem (17.3%) and amoxicillin/clavulanate (9.2%). All the isolates were susceptible to vancomycin and levofloxacin. Multiple drug resistance was observed mostly in types 19F, 23F, 6B and 14. The application of heptavalent pneumococcal conjugate vaccine (PCV7) covered 68.0% of all IPD cases, 42.7% of the penicillin-nonsusceptible S. pneumoniae (PNSSP), and 48.0% of the multiple drug resistant (MDR) isolates. The highest PNSSP prevalence and highest PCV7 coverage were in children aged <2 years. Antibiotic resistance was common among invasive isolates of S. pneumoniae in Zahedan. The present study suggests that the introduction of anti-pneumococcal conjugate vaccines into immunization programme would likely lead to a significant reduction of IPD- associated morbidity among children in Zahedan. Key words: Antimicrobial resistance, invasive pneumococcal disease, serotype, Streptococcus pneumoniae.

Antimicrobial susceptibility of bacterial pathogens associated with community-acquired respiratory tract infections in Asia: report from the Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS) study, 2009–2010

A multicentre resistance surveillance study [Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS)] investigating the susceptibilities of 2963 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, meticillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus spp. from Asia against 12 antimicrobial agents was undertaken from 2009 to 2010. Based on the breakpoints for oral penicillin V recommended by the Clinical and Laboratory Standards Institute, the prevalence of penicillin-non-susceptible S. pneumoniae (PNSSP) ranged from 46% to 100%. Azithromycin and clarithromycin exhibited variable resistance rates of 0–88% against S. pneumoniae, 0–57% against MSSA and 0–76.5% against Streptococcus spp. isolates. The prevalence of extended-spectrum β-lactamase-producing K. pneumoniae varied from 5.1% to 58.5%. β-Lactamase production rates amongst H. influenzae isolates ranged from 15% to 46.6% and amongst M. catarrhalis isolates from 90% to 100%. Amongst M. catarrhalis isolates, macrolide resistance and cefaclor resistance rates of 5.8% and 1.2%, respectively, were found, mainly in Mainland China. Levofloxacin resistance rates of 0–3.9% with a MIC90 (minimum inhibitory concentration causing inhibition of 90% of isolates) of 1–2mg/L and moxifloxacin resistance rates of 0–1.7% with a MIC90 of 0.125–0.5mg/L were found amongst PNSSP isolates. Moxifloxacin was very active against Streptococcus spp., H. influenzae and M. catarrhalis isolates, with MIC90 values of 0.125–0.25, 0.032–0.5 and 0.064–0.125mg/L, respectively. These results from the CARTIPS study have confirmed some significant regional differences in the antimicrobial susceptibilities of S. pneumoniae, MSSA, K. pneumoniae, H. influenzae and Streptococcus spp. and emphasise the importance of antimicrobial surveillance programmes for guiding empirical therapy and for focusing interventional control of antimicrobial resistance in distinct geographic areas.

Antimicrobial resistance surveillance study among Streptococcus pneumoniae clinically isolated from 14 teaching hospitals in 2005-2008 in China

Objective To investigate antimicrobial resistance among Streptococcus pneumoniae clinically isolated from 14 teaching hospitals located at different areas in China in 2005-2008 and to give logical guidance for clinical empirical therapy.Methods A total of 1 317 non-repetitive S.pneumoniae isolates in 14 teaching hospitals from 2005-2008 were collected and sent to the central lab for reidentification and susceptibility testing, including 271 isolates collected in 2005, 391 isolates collected in 2006, 363 isolates collected in 2007 and 292 isolates collected in 2008. Most of the isolates were from community-acquired respiratory tract infections, which were isolated from outpatient or emergency department patients with respiratory tract infections or those patients with respiratory tract infections within ≤48 hours hospitalization.The districts where the organisms were isolated include North China, Northeast China, South China, Central and Northwest China and East China.The patients included adults, teenagers and children.The minimum inhibitory concentrations (MICs) or inhibitory zone diameter of 17 antimicrobial agents were determined by Etest method, agar dilution method or disk diffusion method.WHONET5.5 software was used to analyze susceptibility rate, intermediate rate, resistance rate, MIC50 and MIC90.Results Linezolid (100%) and fluoroquinolones (95.2%-99.7%) showed excellent activities against S.pneumoniae.Among β-lactams, amoxicillin-clavulanic acid remained high activities (73.8%-92.1%),followed by penicillin, ceftriaxone and cefepime with year-over-year decrease in activities.The activities of three second-generation cephalosporins were low (36.3%-38.4% in 2008).The activities of erythromycin, azithromycin, clindamycin, trimethoprim/sulfamethoxazole and tetracycline against S.pneumoniae were poor and decreased year over year.The incidence of penicillin non-susceptible S.pneumoniae (PNSP) was increasing especially for PISP (from 4.4% in 2005 to 20.2% in 2008).The incidence of PNSP in North China was low (6.0%), while this value were high in central China and East China (30.1% and 38.7%, separately).The incidence of PNSP in adults (15.7%) was obviously lower than that in children(≤5 years:33.0%) and teenagers (6-17 years:38.2%).Conclusions linezolid and fluoroquinolones showed excellent in vitro activity against S.pneumoniae, followed by penicillin and cephalosporins with year-over-year decrease of activity. Clinicians should pay more attention when using those antimicrobial agents with poor activity against S.pneumoniae, which include macrolides, clindamycin, trimethoprim/sulfamethoxazole and tetracycline. Key words: Streptococcus pneumoniae; Drug resistance,bacterial; Hospitals,teaching

Serotype distribution and resistance to beta-lactams of Streptococcus pneumoniae isolated from children in Beijing, Shanghai and Guangzhou, 2000 - 2002

The present study was designed to investigate the situation of serotype distribution and beta-lactam antibiotics resistance of Streptococcus pneumoniae (S. pneumoniae) isolated from Chinese children, and to further understand the significance of vaccine for preventing infection caused by the bactria and controlling the resistance to antibiotics. Nasopharageal swab specimens were collected from randomly selected less than 5-year-old out-patients with upper respiratory infection in Beijing, Shanghai and Guangzhou, 2000 - 2002. Capsular typing was performed by the Quellung reaction tested using a simplified chessboard system for typing of S. pneumoniae. The coverage rate of the 7-valent pneumococcal conjugate vaccine (4, 6B, 9V, 14, 18C, 19F and 23F) was calculated. Antibiotic susceptibility was determined by E-test MIC method for beta-lactam antibiotics (penicillin, amoxicillin/clavulanic acid, cefaclor, cefuroxime and ceftriaxone). Totally 625 pneumococcal strains were typed. Serogroup 19, including 121 strains, was the most frequent serogroup observed (19.4%). Other frequently observed serotypes/serogroups in decreasing order of frequency were serotype/serogroups 23 (15.4%), 6 (13.3%), 14 (6.6%) and 15 (4.3%). Of all these isolates, about 57.6% (360/625) were in the 7-valent conjugate vaccine. Only 1, 6 and 12 strains were serotypes/serogroups 4, 9 and 18, respectively. The coverage rate for the 7-valent vaccine of penicillin nonsusceptible S. pneumoniae (PNSP) was higher than penicillin susceptible S. pneumoniae (PSSP) (73.2% and 46.1%). Serogroups 19 and 23, without other serotypes/serogroups, were significantly associated with PNSP (serogroup 19 accounted for 29.1% of PNSP and 12.2% of PSSP; serogroup 23 accounted for 23.8% of PNSP to 9.2% of PSSP). Overall, 140 strains (22.4%) could not be typed by using the chessboard system, and 117 strains (18.7%) were identified as other 28 kinds of serotype/serogroup. The strains showed different resistance change for beta-lactam antibiotics according to different serotype/serogroup during the three years. Serotype/Serogroup 19, 23, 6, 14 and 15 were the common types among the pneumococcal strains isolated from Chinese children. Serogroups 19 and 23 were significantly associated with PNSP. The 7-valent pneumococcal conjugate vaccine could cover most of the islotes.

Phenotypic and molecular analysis of penicillin-nonsusceptible Streptococcus pneumoniae isolates in Poland.

beta-Lactams are the drugs of choice for the treatment of infections caused by the important bacterial pathogen Streptococcus pneumoniae. The recent growth of resistance of this organism to penicillin observed worldwide is of the highest concern. In this study, using 887 surveillance pneumococcal isolates recovered in Poland from 1998 to 2002, we observed the increase in penicillin nonsusceptibility from 8.7% to 20.3%. All of the 109 penicillin-nonsusceptible S. pneumoniae (PNSP) isolates identified, together with 22 archival PNSP isolates from 1995 to 1997, were subsequently analyzed by susceptibility testing, serotyping, profiling of pbp genes, pulsed-field gel electrophoresis, and multilocus sequence typing (MLST). Four predominant serotypes, serotypes 6B, 9V, 14, and 23F, characterized 85.5% of the isolates. MLST revealed the presence of 34 sequence types, 15 of which were novel types. Representatives of seven multiresistant international clones (Spain(23F)-1, Spain(6B)-2, Spain(9V)-3, Taiwan(23F)-15, Poland(23F)-16, Poland(6B)-20, and Sweden(15A)-25) or their closely related variants comprised the majority of the study isolates. The spread of Spain(9V)-3 and its related clone of serotype 14/ST143 has remarkably contributed to the recent increase in penicillin resistance in pneumococci in the country.

Antimicrobial resistance patterns and serotype distribution of invasive Streptococcus pneumoniae isolates from children in Taiwan from 1999 to 2004

Streptococcus pneumoniae causes substantial morbidity and mortality worldwide. Because only limited data are available for the antibiotic resistance patterns and seroepidemiology of invasive S. pneumoniae isolates in Taiwanese children, this national surveillance of invasive pneumococcal infections in children was conducted during a 5-year period. Invasive isolates of S. pneumoniae were obtained from sterile sites (yielding blood and cerebrospinal, pleural, and intra-articular fluids) in children (aged ≤14 years) at a total of 40 regional hospitals and medical centers distributed throughout Taiwan. The collection period was between July 1999 and June 2004, with a total of 286 isolates (including 30 cerebrospinal fluids) collected. All the samples were sent to the Center for Disease Control in Taipei for serotyping and susceptibility testing. Of the 286 S. pneumoniae isolates studied, the 5 most common serotypes were 14 (28.3%), 23F (21.0%), 6B (17.1%), 19F (13.6%), and 3 (4.9%). Intermediate- and high-level penicillin resistance was determined for 50.7% and 25.5% of the isolates, respectively. Isolate resistance was demonstrated to erythromycin (93%), tetracycline (82.2%), trimethoprim/sulfamethoxazole (79.4%), cefotaxime (11.2%), and levofloxacin (0.3%). Multiple drug resistance was found for each serotype, but mostly in types 14, 23F, 6B, and 19F. Overall, 85.0% of the serotypes, 90.8% of the penicillin-nonsusceptible S. pneumoniae (PNSSP), and 90.1% of the multiple drug-resistant (MDR) isolates were covered by the heptavalent pneumococcal conjugated vaccine (PCV7). In this study, we found a diverse pulse-field gel electrophoresis pattern among MDR isolates: a high prevalence of drug resistance and a continued increasing trend in penicillin resistance among nationwide pneumococcal isolates from children in Taiwan. The highest prevalence of invasive pneumococcal disease was in children aged 2 to 5 years, and the highest PNSSP prevalence and highest PCV7 coverage were in children aged <2 years. In terms of reducing the risk of invasive pneumococcal illness in Taiwan, the use of PCV7 is likely to have a beneficial effect similar to that obtained in countries that have used it.

Résistance aux antibiotiques de Streptococcus pneumoniae à la Réunion en 2004

Objective and method. – Available data from the Southern Reunion Island Medical Group was processed to assess the evolution of Streptococcus pneumoniae resistance to antibiotics since 1994 when the first penicillin-non-susceptible S. pneumoniae (PNSSP) was identified. In addition, 249 strains, isolated between 1998 and 2004, were tested against telithromycin and moxifloxacin. Results. – Between 1994 and 2004, the percentage of PNSSP increased from 0 to 59.2%. Among PNSSP, 13.9% were resistant strains in 2004 with MICs < 4 μg/ml. Before 2001 the rate of resistance to penicillin was superior to 50%. In 2004, 15.8 and 8.7% of the isolated strains were of decreased susceptibility to amoxicillin and cefotaxime respectively while none were resistant to either treatment. Other antibiotics followed the pattern of resistance to penicillin. Between 1998 and 2004, resistance to erythromycin decreased from 42.5 to 35.1%, from 35.1 to 22.8% for cyclins, from 18.8 to 8.8 for chloramphenicol, and from 38.3 to 12.3% for cotrimoxazole. All tested strains were susceptible to both telithromycin and moxifloxacin. Conclusion. – Amoxicillin remains efficient for all strains isolated in the Reunion Island in 2004. The presence of strains with decreased susceptibility to third generation cephalosporins implies combination with vancomycin for empirical treatment of pneumococcal meningitis. Moxifloxacin can be used when using a fluoroquinolone is justified. Telithromycin is efficient even on strains resistant to erythromycin and consequently this molecule can be prescribed in the case of a required macrolide treatment.

Resistant Organisms and Otitis Media

To the Editors: Treatment of AOM in the current era of high prevalence of antibiotic-resistant Streptococcus pneumoniae is a great concern and an issue of controversy. A major step towards reducing nonjudicious antibiotic treatment of this infection has been the recognition that antibiotic treatment can be postponed and even omitted in many cases. Yet antibiotic prescriptions for this indication are currently still very frequent, and nonjudicious treatment of this disease continues to contribute to the increase in resistance rate among pathogens. One frequently measured outcome is nasopharyngeal carriage of resistant pathogens after different antibiotic treatments, because such a carriage constitutes a potential source of spread of resistant pathogens in the community. In the study by Toltzis et al,1 4 antimicrobial regimens frequently used in the treatment of acute otitis media (AOM) (amoxicillin, ceftriaxone, cefprozil and azithromycin) were compared, and the outcomes of nasopharyngeal colonization by penicillin-nonsusceptible S. pneumoniae (PNSSP) and in particular penicillin-resistant S. pneumoniae (PRSP) were measured. Although the relative proportion of PRSP of all S. pneumoniae isolated was higher in the amoxicillin group, no significant difference was observed in the prevalence rate of PRSP among the children treated with all 4 regimens during the follow-up period (up to 30 days), when the 4 treatment groups were compared. Neither was there any difference in PRSP carriage rates between the treatment groups. In fact, the only antibiotic that reduced PNSSP carriage was amoxicillin. Because about 33% of PNSSP and 66% of PRSP in the United States are also macrolide-resistant,2,3 missing information in the report by Toltzis et al that is crucial is the carriage rate of macrolide-resistant and multidrug-resistant S. pneumoniae during the period after treatment. In fact, because one of the treatment arms was azithromycin, it is surprising that macrolide resistance (and multidrug resistance) rates were not reported or at least that the reason why they were not reported was not provided. In communities in which macrolide resistance of S. pneumoniae is low, this may not be significant, but in populations with higher prevalence rates (as has been reported in the United States and many countries in Europe), this information is essential. Toltzis et al4 calculated both the simple odds ratio (ORs) and the conditional odds ratio (ORc). Because there was no change in the absolute number of PRSP isolates in each group and thus of the prevalence rate of PRSP, and even the change in PNSSP rates were not significant, the pairwise comparisons of ORs indeed did not detect any differences between the groups (P > 0.29). A recent review5 emphasized how misleading the use of ORc alone can be in interpreting data on carriage and spread of antibiotic-resistant organisms. Toltzis et al used the ORc to claim that acquisition of PRSP was higher in the amoxicillin-treated group, whereas the data show that in the amoxicillin-treated group absolute numbers of PNSP decreased. However, both PNSP and PSSP decreased, but PRSP as a subgroup did not change; the proportion of PRSP increased. The acquisition rate of PNSP or any other subgroup was not measured. In fact, without the use of molecular measures, or at least serotyping, one cannot really calculate acquisition or eradication rates of S. pneumoniae given that both spontaneous and antibiotic-induced eradication and acquisition of new strains are common. Therefore the conclusions drawn by the authors (that amoxicillin administration, compared with the other 3 regimens, resulted in a larger shift toward PRSP colonization and might promote the dissemination of the nonsusceptible phenotype) do not correspond to their results. To date, the published data still support the use of high dose amoxicillin given at high doses (90–100 mg/kg/d, with or without clavulanate)6,7 as the primary treatment of AOM. This regimen is still regarded as optimal when considering both the efficacy of the antimicrobial regimen and the population dynamics associated with carriage and spread of antibiotic-resistant S. pneumoniae. Ron Dagan, MD Soroka University Medical Center The Faculty of Health Science Ben-Gurion University of the Negev Beer-Sheva, Israel Gili Regev-Yochay, MD Ethan Rubinstein, MD Sheba Medical Center Tel-Hashomer, Israel

High Prevalence of Antibiotic Resistance in Isolates from the Middle Meatus of Children and Adults with Acute Rhinosinusitis

The pathogens in acute rhinosinusitis are similar worldwide. An increase in antibiotic resistance has been shown in a large number of studies in recent years. The prevalence of resistance varies greatly in different countries. This study was performed to determine the endemic prevalence of antibiotic resistance in pathogens of acute rhinosinusitis in Taiwan. Middle meatus discharge was taken for aerobic culture in 133 outpatients with the diagnosis of acute rhinosinusitis. One hundred two isolates of pathogens were found, including three major bacteria: Haemophilus influenzae (37.3%), Streptococcus pneumoniae (28.4%), and Moraxella catarrhalis (11.8%). Polymicrobial infections and positive cultures occurred more frequently in pediatric patients, as did recovery of M. catarrhalis infection. An extremely high percentage of resistance to first-line antibiotics was noted, viz., penicillin-nonsusceptible S. pneumoniae (PNSSP) (72.4%), ampicillin-resistant H. influenzae (60.5%), and M. catarrhalis (58.3%). The high prevalence of drug resistance is a great threat to public health. Antibiotic use should be more prudent, especially in pediatric patients, who were found to be more susceptible to bacterial rhinosinusitis and multiple pathogenic infection.

Antibiotic-resistant Streptococcus pneumoniae in the heptavalent pneumococcal conjugate vaccine era: predictors of carriage in a multicommunity sample.

Despite immunization with heptavalent pneumococcal conjugate vaccine (PCV7), the rising prevalence of antibiotic resistance makes Streptococcus pneumoniae a continuing threat to child health. Data on carriage of resistant organisms by healthy children in communities in which immunization with PCV7 has been implemented will help to define and decrease these risks further. Children who were <7 years old, resided in a study community, and presented for routine well care or a "sick" visit between March 13 and May 11, 2001, at 31 primary care practices in 16 geographically distinct Massachusetts communities were studied. Consenting parents provided demographic information and data on potential risk factors for carriage of S pneumoniae and of penicillin-nonsusceptible S pneumoniae (PNSP). S pneumoniae isolates from nasopharyngeal specimens were tested for resistance to commonly used antibiotics including penicillin, ceftriaxone, erythromycin, and trimethoprim/sulfamethoxazole. Isolates were serotyped and grouped into PCV7-included serotypes, potentially cross-reactive serotypes (ie, an organism of a serogroup included in the vaccine), or non-PCV7 serotypes. Diagnosis on the day of collection, history of recent antibiotic use, and history of PCV7 immunization were obtained by chart review. Separate bivariate and multivariate analyses were performed to identify correlates of colonization with S pneumoniae and colonization with PNSP, accounting for clustering within communities. S pneumoniae was isolated from the nasopharynx of 190 (26%) of the 742 children studied. Of the 166 tested, 33% were nonsusceptible to penicillin, with 14% showing intermediate susceptibility (minimum inhibitory concentration [MIC] 0.12-1.0) and 19% fully resistant (MIC > or =2). Nonsusceptibility to other antibiotics was common, including ceftriaxone (14%), erythromycin (22%), and trimethoprim/sulfa (31%); 20% of S pneumoniae isolates were not susceptible to > or =3 antibiotics. Thirty-six percent of isolates were of serotypes covered by PCV7; 30% were of PCV7 serogroups and potentially cross-reactive, but not 1 of the 7 included serotypes; and 34% were unrelated to PCV7 serogroups. Nonsusceptibility to penicillin was more common in PCV7-included strains (45%) and potentially cross-reactive strains (51%) than in non-PCV7 serotypes (8%). Risk factors for PNSP colonization included child care attendance (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 2.3-6.5), current respiratory tract infection (OR: 4.7; 95% CI: 2.5-8.6), and recent antibiotic use (OR: 1.7; 95% CI: 1.0-2.8). PCV7 immunization was associated with decreased carriage of PCV7-included serotypes but not with an overall decrease in S pneumoniae colonization or with a decline in PNSP colonization. In this multicommunity sample, pneumococcal antibiotic resistance was common and was most frequently found in PCV7-included and PCV7 serogroup strains. The long-term impact of PCV7 immunization will be partially determined by the protection that it affords against invasive infection with potentially cross-reactive serotypes, as well as the virulence and future resistance patterns of unrelated serotypes.

Invasive pneumococcal infections: a clinical and microbiological analysis of 53 patients in Taiwan

To track penicillin susceptibility among Streptococcus pneumoniae causing invasive diseases and to evaluate risk factors for antibiotic resistance. A retrospective study was performed in a medical center of all patients with invasive pneumococcal infections based on positive microbiological findings, confirmed by appropriate clinical and laboratory findings. MICs of penicillin and ceftriaxone were determined and interpreted by NCCLS methodology. Fifty-three episodes of invasive S. pneumoniae infections (ISPI) among 22 children and 31 adults were identified. The disease patterns of ISPI were similar between children and adults, and the most common modes were pneumonia (70%) and primary bacteremia (23%). The rate of penicillin-nonsusceptible S. pneumoniae (PNSP) isolated from pediatric patients was higher than that in adult patients (95.5% vs. 54.8%, P < 0.001). This finding was correlated to prior antibiotic use that was more common in children (36.4%) than in adults (18.9%). The rate of penicillin-resistance among S. pneumoniae isolates (PRSP) was extremely high in this area: 45.5% from pediatric patients and 41.9% from adult patients. More adults (90.3%) with ISPI had major underlying diseases than children (4.5%). This may explain why adult patients tended to run an unfavorable outcome (mortality rate, 51.6% and 4.5% in adults and children, respectively), although most of the cases with empyema were children. None of the patients enrolled in this study received pneumococcal vaccination. We suggest that vaccines be administered for young children and the elderly with major underlying diseases to prevent ISPI.

Microbiology of acute otitis media recently treated with aminopenicillins.

Sparse recent data are available in the United States regarding the pathogens of acute otitis media (AOM) most likely to be recovered from children recently treated with the two most frequently prescribed antibiotics, amoxicillin or amoxicillin/clavulanate (AMC). Of the 704 rural Kentucky children with culture-positive AOM who underwent a single tympanocentesis or culture of otorrhea between 1992 and 1998, 96 pathogens were recovered from 90 children during therapy or within 7 days posttherapy with an aminopenicillin. Identification and susceptibility testing of AOM pathogens were performed by routine National Committee for Clinical Laboratory Standards methods. Pathogens recovered from children with AOM recently treated (0 to 7 days) with amoxicillin (n = 38) and AMC (n = 58), respectively, were as follows: Haemophilus influenzae (beta-lactamase-negative), 16 and 29%; H. influenzae (beta-lactamase-positive), 11 and 22%; penicillin-susceptible Streptococcus pneumoniae, 26 and 12%; intermediately penicillin-nonsusceptible S. pneumoniae (PNSP), 20 and 10%; resistant PNSP 13 and 17%; Moraxella catarrhalis (beta-lactamase-positive), 13 and 7%; and Streptococcus pyogenes, 3 and 2%. H. influenzae was also isolated from 8 (75%) of 12 children treated with high dose AMC ( approximately 80 mg/kg/day amoxicillin component). Significantly fewer children recently treated with amoxicillin were otitis-prone than those given AMC (24% vs. 74%, P < 0.0001). The predominant pathogen recovered from children with AOM recently treated with amoxicillin was S. pneumoniae (59%) rather than beta-lactamase-producing organisms (24%). H. influenzae was the predominant (51%) pathogen, rather than PNSP (27%), recovered from children recently treated with AMC.