Impact of cotrimoxazole on non-susceptibility to antibiotics in Streptococcus pneumoniae carriage isolates among HIV-infected mineworkers in South Africa.

OBJECTIVES: To investigate risk factors for pneumococcal carriage and non-susceptibility among HIV-infected mineworkers in South Africa. METHODS: In a cross-sectional study, HIV clinic attendees were questioned about risk factors for pneumococcal carriage and antimicrobial non-susceptibility. Oropharyngeal and nasopharyngeal swabs were taken for pneumococcal culture, serotyping and susceptibility testing. RESULTS: Among 856 participants (854 male, median age 41.5years, median CD4 290cells/mm(3)), 294 (34.3%) were receiving cotrimoxazole prophylaxis. Overall, 75/856 (8.8%) carried S. pneumoniae; among those taking vs. not taking cotrimoxazole, 8.2% vs. 9.1% were carriers. Risk factors for pneumococcal carriage were living with a child (adjusted OR 2.12, 95% CI 1.06-4.62) and recent hospitalisation (adjusted OR 1.80; 95% CI 0.98-3.30). Among participants not taking cotrimoxazole, the prevalence of carriage was higher in individuals with lower CD4 counts. Comparing participants taking cotrimoxazole vs. not, 60.9% vs. 22.4% (p=0.001) isolates were non-susceptible to cotrimoxazole and 30.4% vs. 8.2% were non-susceptible to penicillin (p=0.014). Thirty three/72 (45.8%) isolates were paediatric serotypes/groups. Nasopharyngeal compared with oropharyngeal swabs had higher sensitivity in detecting carriage (53/75, 70.7% vs. 31/75, 41.3%), and adding oropharyngeal sampling increased detection from 6.2% to 8.8%. CONCLUSIONS: Non-susceptibility to cotrimoxazole and penicillin was more common among isolates from participants taking cotrimoxazole prophylaxis. Surveillance for antimicrobial susceptibility is important where prophylaxis is used. Treatment for pneumococcal disease should take into account a higher risk of non-susceptibility to antibiotics amongst individuals taking cotrimoxazole prophylaxis.

Prevalence of serotypes and molecular epidemiology of Streptococcus pneumoniae strains isolated from children in Beijing, China: identification of two novel multiply-resistant clones.

Three-hundred and seventy-six strains of Streptococcus pneumoniae isolated from clinical specimens and nasopharyngeal swabs from children at daycare centers and hospitals in Beijing China, between January 1997 and March 1998, were serotyped. Twenty-seven different serotypes were identified. The most prevalent serotypes in the carriage isolates were 6A, 19F, 23F, and 15 and were found in 66.8% of cases. Serotype data indicate that 51.8% of carrier strains would be included in the 11-valent conjugate vaccine formulation, while inclusion of vaccine-related serotypes, increased the potential vaccine coverage to 79.4%. Serotypes 7, 6B, 23F, 19F, 15, and 3 accounted for 62% of clinical strains, with 70% vaccine-related serotypes. DNA fingerprinting of 47 penicillin resistant and 71 penicillin-susceptible/macrolide-resistant strains by BOX polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE), and penicillin binding protein (PBP)-fingerprinting identified two novel clones: one a serotype 23F multiresistant clone resistant to penicillin, tetracycline, erythromycin, clindamycin, and variably resistant to chloramphenicol and trimethoprim-sulphamethoxazole; and the second a multiresistant penicillin-susceptible, macrolide-resistant serotype 6A clone, highly resistant also to tetracycline, clindamycin, and trimethoprim-sulphamethoxazole. The macrolide resistance determinant in 89% of erythromycin-resistant strains tested (penicillin-susceptible and penicillin-resistant) was the erm gene, both the erm and mef genes were simultaneously found in 6%, and mef alone in 3.4%. The data demonstrates that macrolide resistant strains in China include clonal strains and strains with dual mef and erm resistance determinants.

Serotype 19f multiresistant pneumococcal clone harboring two erythromycin resistance determinants (erm(B) and mef(A)) in South Africa.

One hundred eighteen erythromycin-resistant Streptococcus pneumoniae (ERSP) strains (MICs of > or = 0.5 microg/ml) from five laboratories serving the private sector in South Africa were analyzed for the genes encoding resistance to macrolides. Sixty-seven ERSP strains (56.8%) contained the erm(B) gene, and 15 isolates (12.7%) contained the mef(A) gene. Thirty-six isolates (30.5%) harbored both the erm(B) and mef(A) genes and were highly resistant to erythromycin and clindamycin. DNA fingerprinting by BOX-PCR and pulsed-field gel electrophoresis identified 83% of these strains as belonging to a single multiresistant serotype 19F clone.

Antimicrobial resistance of nasopharyngeal isolates of Streptococcus pneumoniae and Haemophilus influenzae from children in the Central African Republic.

BACKGROUND: To assist the Central African Republic (CAR) develop national guidelines for treating children with pneumonia, a survey was conducted to determine antimicrobial resistance rates of nasopharyngeal isolates of Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI). Secondary purposes of the survey were to identify risk factors associated with carriage of a resistant isolate and to compare the survey methods of including only children with pneumonia vs. including all ill children. METHODS: A cross-sectional survey of 371 ill children was conducted at 2 outpatient clinics in Bangui, CAR. RESULTS: In all 272 SP isolates and 73 HI isolates were cultured. SP resistance rates to penicillin, trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline and chloramphenicol were 8.8, 6.3, 42.3 and 9.2%, respectively. All penicillin-resistant SP isolates were intermediately resistant. HI resistance rates to ampicillin, TMP-SMX and chloramphenicol were 1.4, 12.3 and 0%, respectively. The most common SP serotypes/groups were 19, 14, 6 and 1; 49% of HI isolates were type b. History of antimicrobial use in the previous 7 days was the only factor associated with carriage of a resistant isolate. Resistance rates were similar among ill children regardless of whether they had pneumonia. CONCLUSIONS: Resistance rates were low for antimicrobials recommended by the World Health Organization for children with pneumonia. We recommended TMP-SMX as the first line treatment for pneumonia in CAR because of its low cost, ease of dosing and activity against malaria.

Impact of human immunodeficiency virus type 1 on the disease spectrum of Streptococcus pneumoniae in South African children.

BACKGROUND: HIV-infected children are at increased risk of developing invasive Streptococcus pneumoniae disease. OBJECTIVE: To determine the impact of the HIV epidemic on the epidemiology of invasive pneumococcal disease in hospitalized African children. METHODS: Children <12 years of age with invasive pneumococcal disease were enrolled between March, 1997, and February, 1999. RESULTS: The seroprevalence of HIV was 64.9% (146 of 225). In children with pneumococcal isolates from serogroups 6, 9, 14, 19 or 23 (pediatric serogroups), pneumonia and pneumonia with concurrent meningitis was more common in HIV-infected children (P = 0.03 and P = 0.003, respectively), whereas septic shock occurred more often in HIV-uninfected children (P = 0.0003). The overall burden of severe invasive pneumococcal disease was 41.7 (95% confidence interval, 26.5 to 65.6) fold increased in HIV-infected compared with HIV-uninfected children. Reduced susceptibility to penicillin (45.91% vs. 27.9%, P = 0.009), trimethoprim-sulfamethoxazole (44.5% vs. 19.0%, P = 0.0002) and multiple drug resistance was more common in HIV-infected than in HIV-uninfected children (24.0% vs. 6.4%, P = 0.01), respectively. The increased burden of disease and reduced antibiotic susceptibility of pneumococcal isolates in HIV-infected children was because of a heightened susceptibility to disease caused by pediatric serogroups in these children than in HIV-uninfected children (P = 0.01). Although the case fatality rates did not differ between HIV-infected and -uninfected children, mortality in HIV-infected children with advanced AIDS (Stage C, 22 of 61; 36.1%) was greater than that in children with moderate AIDS (Stage B, 12 of 85; 14.1%, P = 0.002). CONCLUSIONS: In children with invasive pneumococcal disease caused by the pediatric serogroups, HIV-infected children have more antibiotic-resistant isolates and have a different clinical presentation than do HIV-uninfected children.

Trends in antimicrobial resistance and serotype distribution of blood and cerebrospinal fluid isolates of Streptococcus pneumoniae in South Africa, 1991-1998.

OBJECTIVE: Since 1979, the South African Institute for Medical Research (SAIMR) has served as the national reference center for pneumococcal serotyping and monitoring of antibiotic resistance trends. This study documents trends in antimicrobial resistance in pneumococci isolated from blood or cerebrospinal fluid (CSF) between 1991 and 1998 in South Africa. METHODS: Pneumococcal isolates (n = 7406) from either blood or CSF were sent to the SAIMR reference laboratory for serotyping. The isolates were evaluated for resistance to penicillin, chloramphenicol, tetracycline, erythromycin, clindamycin, and rifampicin. RESULTS: Resistance to one or more antibiotics increased significantly from 19% in 1991 to 1994 to 25% in 1995 to 1998 in all ages, and in children from 32% to 38% (P < 10[-6]). Although penicillin resistance did not increase in children (28.1% vs. 28.9%), penicillin resistance in all ages increased from 9.6% to 18.0%. Significant increases in resistance to chloramphenicol, tetracycline, erythromycin, and rifampicin also were seen in both groups. Multiple resistance increased significantly, from 2.2% to 3.8%. The proportion of isolates with intermediate or high-level penicillin resistance remained constant during the surveillance period. Erythromycin resistance, predominantly expressed as simultaneous resistance to erythromycin and clindamycin, increased from 1.6% to 2.6%. The percentage of erythromycin-resistant isolates that were resistance to erythromycin alone increased from 10.6% to 28.7%, suggesting the emergence of mefE-mediated resistance. In children 2 years of age and younger, although serogroup 6 remained the most common, there were significant increases in serogroups 19, 18, and 13. The percentage of the total invasive pneumococcal disease in this population that is caused by serogroups found in the nonavalent pneumococcal conjugate vaccine (serogroups 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F) increased from 72% to 91%. CONCLUSIONS: Antibiotic resistance in the pneumococcus is increasing in South Africa, although the proportion of strains with high-level penicillin resistance has not increased. New conjugate vaccines may not only decrease the burden of all pneumococcal disease but, in addition, lower the incidence of antibiotic-resistant disease in South Africa.

Prevalence of nasopharyngeal antibiotic-resistant pneumococcal carriage in children attending private paediatric practices in Johannesburg.

OBJECTIVES: To determine the nasopharyngeal carriage rate, serogroups/types, and antibiotic resistance of Streptococcus pneumoniae in children attending paediatric practices in the private sector in Johannesburg and to relate patterns of resistance to antimicrobial exposure and other demographic characteristics in individual children. DESIGN: A total of 303 children aged from 1 month to 5 years were recruited from eight private paediatric practices in northern Johannesburg. Nasopharyngeal samples were taken and parent interviews were conducted. RESULTS: Pneumococci were isolated from 121 children (40%). The most common serotypes were 6B, 19F, 6A, 23F, 14, and 19A. Carriage was significantly associated with prior hospital admission (odds ratio 1.89) and day care attendance (odds ratio 2.31) and was negatively associated with antibiotic use within the previous 30 days. Antibiotic resistance was found in 84 isolates (69.4%); 45 (37.2%) were multiply resistant. One-third of the pneumococci showed intermediate level resistance to penicillin and 12.4% were highly resistant. There was a high level erythromycin resistance in 38% of the isolates. A total of 94/214 children (42%) had recently used antibiotics and were four times more likely to carry antibiotic-resistant pneumococci (P < 0.05). CONCLUSION: Pneumococcal resistance was significant in this group of children with easy access to paediatric services and antibiotic use. The implication of such high resistance for the treatment of pneumococcal diseases is that high-dose amoxicillin is the preferred empirical oral therapy for treatment of otitis media. Ceftriaxone or cefotaxime should be used in combination with vancomycin for the treatment of meningitis until a cephalosporin-resistant pneumococcal cause is excluded. Intravenous penicillin or ampicillin will successfully treat pneumococcal pneumonia in this population. Antimicrobial resistance among pneumococci colonising children in the private sector has increased dramatically in recent years.

Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine.

The safety, immunogenicity, and impact on carriage of a nonvalent pneumococcal vaccine given at ages 6, 10, and 14 weeks were examined in a double-blind, randomized, placebo-controlled trial in 500 infants in Soweto, South Africa. No serious local or systemic side effects were recorded. Significant antibody responses to all pneumococcal serotypes were observed 4 weeks after the third dose. Haemophilus influenzae type b polyribosylribitol phosphate (geometric mean titer, 11.62 microg/mL) and diphtheria (1.39 IU/mL) antibodies were significantly higher in children receiving pneumococcal conjugate, compared with placebo recipients (4.58 microgram/mL and 0.98 IU/mL, respectively). Nasopharyngeal carriage of vaccine serotypes decreased in vaccinees at age 9 months (18% vs. 36%), whereas carriage of nonvaccine serotypes increased (36% vs. 25%). Carriage of penicillin-resistant pneumococci (21% vs. 41%) and cotrimoxazole-resistant pneumococci (23% vs. 35%) were significantly reduced 9 months after vaccination, compared with controls.

Use of Dorset egg medium for maintenance and transport of Neisseria meningitidis and Haemophilus influenzae type b.

Studies of bacterial meningitis are hampered by the inability to maintain the viability of etiological agents during transport to reference laboratories. The long-term survival rate of 20 isolates of Neisseria meningitidis and Haemophilus influenzae type b (Hib) on Dorset egg medium, supplemented Columbia agar base medium, chocolate agar, and Amies medium was compared with that on 70% GC agar (chocolate) transport medium. N. meningitidis isolates were also inoculated onto 5% horse blood agar, and Hib was inoculated onto Haemophilus test medium. All of the N. meningitidis isolates remained viable on Dorset egg medium for 21 days; viability on the other media was poor after only 7 days. Recovery rates of Hib isolates were similar on Dorset egg and Haemophilus test media (100% after 21 days) and significantly better than on the other media. Dorset egg medium is inexpensive and easy to make and may be invaluable for studies of bacterial meningitis in developing countries.

Nasopharyngeal carriage and antimicrobial resistance in isolates of Streptococcus pneumoniae and Haemophilus influenzae type b in children under 5 years of age in Botswana.

OBJECTIVES: A prospective survey was conducted to determine the prevalence of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae type b in children under 5 years of age in Botswana and to determine the antibiotic resistance patterns of these organisms to commonly used antimicrobial agents. METHODS: Children 2 months to 5 years of age (n = 249) were recruited from outpatient clinics in Gaborone and Francistown, and 29 were sampled from the pediatric wards at Princess Marina (Gaborone) and Nyangabgwe (Francistown) Hospitals. Nasopharyngeal specimens were collected and the carriage and antibiotic resistance of S. pneumoniae and H. influenzae type b were determined. Analyses of risk factors associated with carriage and resistance were performed. RESULTS: Streptococcus pneumoniae was isolated from 69% of the outpatient children in Gaborone and 85% of the children in Francistown; the carriage rate in hospitalized children was 36% and 33% in Gaborone and Francistown, respectively. Approximately half of the isolates at both sites were resistant to at least one antibiotic, the most common being cotrimoxazole and penicillin. Resistance to three or more antibiotics (multiple resistance) was found in less than 10% of the isolates. Most penicillin resistance at both sites was at the intermediate level; however, almost 20% of the isolates demonstrated high-level resistance to cotrimoxazole. The most prevalent serogroups or serotypes of antibiotic-resistant isolates were 14, 19F, 19A, 6A, 6B, and 4. No risk factors for antibiotic resistance were identified. Haemophilus influenzae type b was isolated from 8% of the children in Gaborone and from 3% of the children in Francistown. Almost a third of the isolates were resistant to ampicillin. CONCLUSIONS: The high levels of antibiotic resistance in pneumococci isolated from children in Botswana suggest that the clinical management of meningitis and otitis media with a b-lactam antibiotic may fail in a significant proportion of cases and that empiric first-line use of cefotaxime or ceftriaxone for meningitis and higher dose amoxicillin (90 mg/kg/day) for otitis media is recommended. The levels of penicillin resistance in this study would not impact on the management of pneumonia with amoxicillin.

Long-term survival of Streptococcus pneumoniae at room temperature on Dorset egg medium.

Forty-five isolates of Streptococcus pneumoniae were inoculated on Dorset egg and supplemented Columbia agar base media, incubated overnight at 37 degrees C, and then kept at room temperature (RT; 21 degrees C) or 4 degrees C. Long-term viability was best at RT for both media, with all isolates remaining viable on Dorset egg medium for 44 days; viability was 90 and 57% on Columbia agar base medium after 7 and 30 days. We recommend the use of Dorset egg medium for the maintenance of pneumococci at RT.

Antibiotic resistance of nasopharyngeal isolates of Streptococcus pneumoniae from children in Lesotho.

Villages associated with the Lesotho Highlands Development Agency were randomized with a bias in favour of larger villages, and children < 5 years of age from cluster-randomized households in these villages were chosen for the assessment of antibiotic resistance in pneumococci. Children of the same age group attending clinics in the capital, Maseru, were selected for comparison. Nasopharyngeal cultures of Streptococcus pneumoniae from both groups of children were examined for antibiotic resistance and a questionnaire was used to assess risk factors for the acquisition of resistant strains. Carriage of penicillin- and tetracycline-resistant pneumococci was significantly higher among 196 Maseru children compared with 324 rural children (P < 0.05 and P = 0.01, respectively). Maseru children tended to visit clinics at an earlier age compared with their rural counterparts. The rural children were less exposed to antibiotics (P < 0.01), were less frequently hospitalized (P < 0.001), and rarely attended day care centres (P < 0.001). The very low incidence of antibiotic resistance in rural Lesotho and the higher incidence in Maseru are in stark contrast with the much higher frequencies found in the Republic of South Africa, many European countries, and the USA.

Streptococcus pneumoniae blood culture isolates from patients with and without human immunodeficiency virus infection: alterations in penicillin susceptibilities and in serogroups or serotypes.

We performed a 3-year retrospective study of Streptococcus pneumoniae blood culture isolates recovered at Baragwanath Hospital, Soweto, South Africa, from 1993 to 1995. The study group comprised 457 patients, including 98 children, of known human immunodeficiency virus (HIV) serostatus. Of these patients, 70 (30 [8.4%] of 359 adults and 40 [40.8%] of the 98 children) were infected with penicillin-resistant S. pneumoniae strains (minimal inhibitory concentration, > or = 0.12 microg/mL); 56 of these strains were intermediately resistant to penicillin. HIV-positive patients had significantly more penicillin-resistant isolates than did HIV-negative patients (43 [29.7%] of 145 HIV-positive patients vs. 27 [8.6%] of 312 HIV-negative patients; P < .001); this difference was found for both adults (19% vs. 4.3%; P < .001) and children (53.3% vs. 30.2%; P < .0343). Multiple resistance occurred more frequently in HIV-positive children (P = .02). HIV-positive adults had a statistically significant increase in the percentage of serogroups and serotype usually found in children and commonly associated with antimicrobial resistance, i.e., serotype 14 and serogroups 6, 19, and 23 (48% vs. 28.6%; P < .001). The increased prevalence of serogroups or serotypes usually found in children was also found among penicillin-susceptible strains. These data suggest that HIV-infected adults may again become susceptible to the serogroups or serotypes found in children.

Nasopharyngeal carriage of community-acquired, antibiotic-resistant Streptococcus pneumoniae in a Zambian paediatric population.

The emergence of antibiotic-resistant Streptococcus pneumoniae is an international health problem. Apart from South Africa few data on pneumococcal resistance are available for sub-Saharan Africa. This study examines the nasopharyngeal carriage and prevalence of antibiotic resistance in pneumococci isolated from 260 Zambian children aged < 6 years. Pneumococci were isolated from 71.9% of the children; the odds of carrying organisms were twice as high among children < 2 years of age compared with older children. Antibacterial resistance was found in 34.1% of the isolates; resistance to tetracycline, penicillin, sulfamethoxazole + trimethoprim, and chloramphenicol occurred in 23.0%, 14.3%, 12.7%, and 3.9% of the isolates, respectively. Only 4% of the isolates were resistant to three drugs. High-level resistance was found in all isolates resistant to tetracycline; but only intermediate level penicillin resistance was found. A total of 11.1% of the isolates demonstrated intermediate resistance to sulfamethoxazole + trimethoprim. Children aged < 6 months were less likely to carry antibiotic-resistant organisms. Antibiotic resistance in S. pneumoniae appears to be an emerging public health problem in Zambia, and the national policy for the empirical treatment of pneumococcal meningitis and acute respiratory tract infections may need to be re-evaluated. The establishment of ongoing surveillance to monitor trends in pneumococcal resistance should be considered.

PIP: Pneumococcal pneumonia accounts for up to 25% of deaths in children under 5 years of age in sub-Saharan Africa. This study investigated the nasopharyngeal carriage rate of Streptococcus pneumoniae in a Zambian pediatric population and the prevalence of antibiotic resistance. Enrolled were 260 children under 6 years of age (mean age, 20 months) treated at the University Teaching Hospital in Lusaka, Zambia, in 1994. S. pneumoniae was isolated from the nasopharynx of 187 children (71.9%). The odds of carrying pneumococci were twice as high among children under 2 years of age (76.2%) than older children (59.7%). Overall, 83 (65.9%) of the 126 isolates available for antibiotic resistance profiles were sensitive to the drugs. Resistance to tetracycline, penicillin, sulfamethoxazole plus trimethoprim, and chloramphenicol was found in 23.0%, 14.3%, 12.7%, and 3.9%, respectively, of the isolates. The highest level of resistance was recorded in all isolates resistant to tetracycline. All but one of the multidrug-resistant isolates were serotype 14. Children under 6 months old were least likely to carry antibiotic-resistant organisms. In an anonymous questionnaire completed by 160 mothers, 38% reported they obtained antibiotics without a prescription and 49.4% acknowledged feeling dissatisfied when not given antibiotics to treat their sick child. Ongoing surveillance is recommended in Zambia to ensure that recommended treatment regimens keep pace with trends in antibiotic resistance.

Increasing prevalence of penicillin-resistant pneumococcal infections in children in southern Israel: implications for future immunization policies.

Although penicillin-resistant pneumococci (PR-PnC) are recognized as an increasing problem worldwide, data on the prevalence of these strains among pediatric patients are incomplete. The present study was conducted in southern Israel (1) to investigate the frequency of PR-PnC in invasive and middle ear infections in pediatric patients and (2) to assess the impact of resistance on the potential role of the candidate conjugate vaccines in preventing childhood PR-PnC infections. A total of 120 blood or cerebrospinal fluid isolates from 1987 to 1993 and 78 ear isolates from 1992 to 1993 were serogrouped and tested for susceptibility to antibacterial agents. The prevalence of PR-PnC among invasive isolates increased from 16% in the years 1987 to 1991 to 36% in 1992 to 1993 (P = 0.019). This increase was noted mainly for intermediately resistant strains (minimal inhibitory concentration, 0.12 to 1.0 micrograms/ml) whereas the prevalence of highly resistant strains was 3 and 2% for the 2 periods, respectively. The prevalence of PR-PnC among ear isolates in 1992 to 1993 was 42%. Resistance to other antimicrobial agents (one or more of the following: tetracycline, erythromycin, clindamycin and chloramphenicol) was found in 16 (8%) isolates, and multiple resistance (resistance to > or = 3 antibacterial agents) was found in 9 (5%) isolates. Sixty-five (99%) of the 66 resistant isolates belong to Serogroups 6, 14, 19 and 23. The prevalence of these 4 serogroups rose from 37% in 1987 to 1991 to 66% in 1992 to 1993 (P = 0.043). This rise was mainly because of Serogroup 23, the prevalence of which rose from 3% in 1987 to 1991 to 23% in 1992 to 1993 (P < 0.001). Eighty-five percent of all isolates belonging to Serogroup 23 were resistant to penicillin. Because Serogroups 6, 14, 19 and 23 are among the commonest pediatric pneumococcal strains, the newly developed conjugate pneumococcal vaccines contain these 4 serogroups. The selection of antibiotic-resistant strains has thus led to a change in the spectrum of serotypes causing invasive disease and to a situation of potential increase in vaccine coverage for the proposed pneumococcal conjugate vaccines.