title: High incidence of antimicrobial resistant organisms including extended spectrum beta-lactamase producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus in nasopharyngeal and blood isolates of HIV-infected children from Cape Town, South Africa.
abstract: BACKGROUND
  There is little information on nasopharyngeal (NP) flora or bacteremia in HIV-infected children. Our aim was to describe the organisms and antimicrobial resistance patterns in children enrolled in a prospective study comparing daily and three times weekly trimethoprim-sulfamethoxazole (TMP-SMX) and isoniazid (INH) or placebo prophylaxis.
  
  
  METHODS
  NP swabs were taken at baseline from HIV-infected children enrolled in the study. Standard microbiological techniques were used. Children were grouped according to previous or current exposure to TMP-SMX and whether enrolled to the study during a period of hospitalization. Blood culture results were also recorded within 12 months of baseline.
  
  
  RESULTS
  Two hundred and three children, median age 1.8 (Interquartile [IQ]: 0.7-4) years had NP swabs submitted for culture. One hundred and eighty-four (90.7%) had either stage B or C HIV disease. One hundred and forty-one (69.8%) were receiving TMP-SMX and 19 (9.4%) were on antiretroviral therapy. The majority, 168 (82%) had a history of hospitalization and 91 (44.8%) were enrolled during a period of hospitalization. Thirty-two subjects (16.2%) died within 12 months of study entry. One hundred and eighty-one potential pathogens were found in 167 children. The most commonly isolated organisms were Streptococcus pneumoniae (48: 22.2%), Gram-negative respiratory organisms (Haemophilus influenzae and Moraxella catarrhalis) (47: 21.8%), Staphylococcus aureus (44: 20.4%), Enterobacteriaceae 32 (14.8%) and Pseudomonas 5 (2.3%). Resistance to TMP-SMX occurred in > 80% of pathogens except for M. catarrhalis (2: 18.2% of tested organisms). TMP-SMX resistance tended to be higher in those receiving it at baseline (p = 0.065). Carriage of Methicillin resistant S. aureus (MRSA) was significantly associated with being on TMP-SMX at baseline (p = 0.002). Minimal inhibitory concentrations (MIC) to penicillin were determined for 18 S. pneumoniae isolates: 7 (38.9%) were fully sensitive (MIC <or= 0.06 microg/ml), 9 (50%) had intermediate resistance (MIC 0.12 - 1 microg/ml) and 2 (11.1%) had high level resistance (MIC >or=2 microg/ml). Fifty percent of Enterobacteriaceae produced extended spectrum beta-lactamases (ESBL) (resistant to third generation cephalosporins) and 56% were resistant to gentamicin. Seventy-seven percent of S. aureus were MRSA. Carriage of resistant organisms was not associated with hospitalization.On multivariate logistic regression, risk factors for colonization with Enterobacteriaceae were age <or= one year (Odds ratio 4.4; 95% Confidence Interval 1.9-10.9; p = 0.0008) and CDC stage C disease (Odds ratio 3.6; 95% Confidence Interval 1.5-8.6; p = 0.005)Nineteen (9.4%) subjects had 23 episodes of bacteremia. Enterobacteriaceae were most commonly isolated (13 of 25 isolates), of which 6 (46%) produced ESBL and were resistant to gentamicin.
  
  
  CONCLUSIONS
  HIV-infected children are colonized with potential pathogens, most of which are resistant to commonly used antibiotics. TMP-SMX resistance is extremely common. Antibiotic resistance is widespread in colonizing organisms and those causing invasive disease. Antibiotic recommendations should take cognizance of resistance patterns. Antibiotics appropriate for ESBL-producing Enterobacteriaceae and MRSA should be used for severely ill HIV-infected children in our region. Further study of antibiotic resistance patterns in HIV-infected children from other areas is needed.
authors.affiliation: Department of Paediatrics, Faculty of Health Sciences, Stellenbosch University, Cape Town South Africa. mcot@sun.ac.za
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wasserman
authors.forename: Juanita
authors.initials: J
authors.lastname: Smit
authors.forename: Andrew
authors.initials: A
authors.lastname: Whitelaw
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Zar
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage; D016470:Bacteremia / Q000453:epidemiology / Q000382:microbiology*; D002353:Carrier State / Q000453:epidemiology / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000453:epidemiology / Q000382:microbiology*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D015994:Incidence; D007223:Infant; D007538:Isoniazid / Q000008:administration & dosage; D016015:Logistic Models; D008297:Male; D016106:Methicillin Resistance; D009305:Nasopharynx / Q000382:microbiology*; D011446:Prospective Studies; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D001618:beta-Lactamases; D007538:Isoniazid