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
Mark F Cotton
Heather J Zar
Division of Medical Microbiology, National Health Laboratory Systems, University of Cape Town
Department of Pathology and National Health Laboratory Systems, Faculty of Health Sciences, Stellenbosch University
Departments of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University
School of Child and Adolescent Health, University of Cape Town
Background: There is little information on nasopharyngeal (NP) flora or bacteremia in HIVinfected 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 trimethoprimsulfamethoxazole (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 0.06 g/ml), 9 (50%)
had intermediate resistance (MIC 0.12 1 g/ml) and 2 (11.1%) had high level resistance (MIC 2
g/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
On multivariate logistic regression, risk factors for colonization with Enterobacteriaceae were age
one year (Odds ratio 4.4; 95% Confidence Interval 1.910.9; p = 0.0008) and CDC stage C
disease (Odds ratio 3.6; 95% Confidence Interval 1.58.6; 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.
Conclusion: 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
ESBLproducing 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
There are few data on nasopharyngeal (NP) flora from
HIV-infected children. Most studies have focused on
specific organisms such as Streptococcus pneumoniae,
Staphylococcus aureus and Haemophilus influenzae, with provision of
limited antibiotic resistance data, mainly to penicillin
. Although antibiotic resistance has been documented
in some of these studies, there is need for more
information. Thus far, there are no studies documenting the
presence of other potential pathogens.
Colonization of the NP by potential respiratory
pathogens S. pneumoniae, H. influenzae, S. aureus and Moraxella
catarrhalis is established early in childhood. Factors
involving colonization and elimination are not well
understood but probably involve adhesive and
immunologic factors . NP colonization with Enterobacteriaceae
occurs in malnourished children and also those from
impoverished environments [7,8]. That NP colonization
precedes invasive disease has been well established in the
rat model , meningococcal meningitis  and for S.
pneumoniae in children [11,2]. Pharyngeal colonization by
Salmonella species in resource-poor settings has also been
linked to invasive disease .
There are few data in HIV-infected children on organisms
causing bacteremia. Madhi et al documented an increased
risk of MRSA and trimethoprim-sulfamethoxazole
(TMPSMX) resistance in HIV-infected compared to uninfected
infants with bacteremic community-acquired pneumonia
in 2000 .
TMP-SMX prophylaxis, given to all HIV-exposed and
infected children from 6 weeks of age to prevent
Pneumocystis jirovecii pneumonia (PCP) has been associated with
NP carriage of multiresistant S. pneumoniae  and
increased colonization with S. aureus . Moreover, its
use for intercurrent infections such as otitis media, is
linked to increased resistance .
The aim of this study was to describe the baseline bacterial
flora and antimicrobial resistance patterns of potentially
pathogenic bacteria in HIV-infected children enrolled in a
prospective study investigating the long-term effects of
TMP-SMX and INH prophylaxis . Secondary aims
were to examine the effects of prior TMP-SMX on NP
organisms and TMP-SMX resistance and to explore
relationships between colonizing flora, nutritional status,
age, extent of HIV disease, and hospitalization status.
Lastly, blood culture isolates, which represent the most
extreme form of invasive disease, were reviewed.
The study population comprised HIV-infected children
aged 8 weeks or older, attending either Red Cross (RCCH)
or Tygerberg Children's Hospitals (TCH) in Cape Town
and recruited for a study of daily versus thrice weekly
TMP-SMX given with Isoniazid (INH) or placebo .
The study commenced in December 2002. Due to
resource constraints, no HIV-uninfected infants were
recruited as controls. The Ethics Committees of Cape
Town and Stellenbosch Universities approved the study.
Written, informed consent was obtained from a parent or
legal guardians prior to enrolment.
At enrolment, note was taken of previous and current
hospitalization, concomitant medication, including
TMPSMX and antiretroviral therapy. According to baseline
TMP-SMX prophylaxis status, subjects were grouped as
follows: 1) no prophylaxis, 2) currently receiving
TMPSMX 3) TMP-SMX not currently used but given in the past.
Race was not documented in subjects. All came from
socio-economically deprived settings and attended public
healthcare facilities. The median household income was
$126 per month, with on average 5 persons per
household, translating into $0.84/person/day and below the
monthly minimum subsistence of $133 defined by the
South African Government. Nearly half (44%) of children
lived in informal settlements .
Subjects were classified for severity of HIV disease and
CD4 cell depletion according to the Centres for Disease
Control and Prevention (CDC) classification system. 
Weight for age Z-score was calculated using Epi-Info 2004,
CDC, Atlanta, GA. Mortality data for the first 52 weeks on
the study was extracted from the trial database. Blood
culture data were obtained from the National Health
Laboratory databases at the two hospitals from a week prior until
52 weeks post enrolment.
NP swabs, (urethral/ENT straight wire swabs transported
in Amies charcoal media (Medical wire & equipment,
Wiltshire, U.K) were collected at baseline according to a
prescribed protocol. A single microbiologist processed all
specimens. Swabs were inoculated on appropriate media
to isolate staphylococci, streptococci (including S.
pneumoniae), H. influenzae, M. catarrhalis and other
Gram-negative organisms. After incubation, organisms were
identified according to routine laboratory procedures.
Susceptibility testing (Kirby-Bauer disc diffusion) was
performed on all isolates and interpreted according to
Clinical Laboratory Standards Institute (CLSI) . For M.
catarrhalis, -lactamase production was determined using
a nitrocephin method (Oxoid, Hampshire, England). The
prescribed quality control strains of the American Type
Culture Collection (ATCC) were used to verify all
susceptibility tests. Extended spectrum beta-lactamase (ESBL)
production was detected using the double disc diffusion
test, by placing a disc with amoxicillin/clavulanate
adjacent to discs with cefotaxime and ceftazidime (1 disc with
each), and looking for synergy between the clavulanic
acid and the cephalosporin . MRSA was detected
using oxacillin discs on salt agar .
Isolates of S. pneumoniae, H. influenzae and M. catarrhalis
were stored at -70C in a glycerol nutrient broth enriched
with 5% horse blood. Broth dilution MIC's were
performed in batches according to CLSI methodology. A
single microbiologist (JS) processed all NP swabs.
M. catarrhalis and H. influenzae were categorized as
Gramnegative respiratory organisms and all Enterobacteriaceae
were grouped together. Subjects with no growth,
contaminated cultures, coagulase negative staphylococci or only
commensals were also combined into a single group.
Descriptive statistics used to summarize ordinal and
continuous variables were the median and interquartile range
(IQR). The chi-square and Fisher's exact tests were used
for analysis of categorical data and the Kruskal-Wallis test
was used for non-parametric one-way analysis of variance.
A multiple logistic regression model was used to
determine risk factors for colonization by predominant
organisms. Odds ratios and 95% confidence intervals were
reported. The model included all factors from bivariate
analyses evaluated a significance level of 0.1. Analyses
with performed using JMP 5.1 (SAS, Cary, CA, USA).
NP cultures were submitted for 203 children. Baseline
demographics are shown in Table 1. Median age was 1.8
(IQ 0.7 4 years. The majority (89.7%) of children had
moderate or severe HIV disease and 78% had CD4 cell
depletion. The median weight for age-Z score (WAZ) was
-1.6. Almost 70% were receiving TMP-SMX at baseline.
The majority of subjects had been hospitalized previously,
with only 38 subjects (18.7%) never having been
hospitalized. Almost half (44.8%) were recruited during a
period of hospitalization. Nineteen (9.4%) children were
on antiretroviral therapy (ART). Thirty-five children
(17.2%) died within 12 months of enrolment.
Infants without prior TMP-SMX were significantly
younger than those on TMP-SMX at baseline (1.3 [IQ:
0.22.1] versus1.9 [IQ: 0.44.4] years) or than those
previously on TMP-SMX (3.2 [IQ: 1.86.3 years) (p =
0.0008). NP organisms and TMP-SMX status are shown in
Table 2. One hundred and eighty-one potential pathogens
were isolated from 167 subjects. Five had two organisms
within a group, such as H. influenzae and M. catarrhalis or
different species of Gram-negative Enterobacteriaceae.
The most common organisms were S. pneumoniae (48:
22%), Gram-negative respiratory organisms (H. influenzae
and M. catarrhalis) (47: 21.7%), S. aureus (44: 20.4%),
and Enterobacteriaceae (32: 14.1%). There were no
significant differences in organisms isolated by TMP-SMX
status, except for P. aeruginosa and Acinetobacter which were
more common in subjects not on TMP-SMX at baseline (p
= 0.01 and 0.048, respectively).
Median age (IQ range)
No previous experience
On drug at baseline
History of exposure
Median weight for age Z-score (IQ range)
Antiretroviral therapy at baseline
Time on therapy
Died within 12 months of enrolment
Patients N = 203
1.8 (0.7 4) years
Risk factors for colonization by predominant organisms
are shown in Table 3. For Enterobacteriaceae, age below a
year (OR 4.4 [1.910.9]) and CDC Stage C disease (OR
3.6 [1.58.6]) were significant factors on multivariate
analysis. For S. aureus, having moderate or severe CD4
depletion was associated with colonization (OR 3.4 (1.3
11.8]). There was a trend towards decreased carriage of
gram-negative respiratory organisms in subjects on
TMPSMX at baseline (OR 0.3 [0.090.9] p = 0.057) and also
with a relative lack of CD4 depletion (CDC
Immunological Class 2 or 3: OR 0.3 [0.10.9] p = 0.005). No risk
factors were identified for S. pneumoniae carriage.
Antibiotic resistance patterns are shown in table 4. One
hundred and forty-two (88%) of 160 isolates tested, were
resistant to TMP-SMX. A high percentage of organisms
were resistant to first line antibiotics used for severe
community acquired infections. Seventy-seven percent of S.
aureus were MRSA and 81% were resistant to gentamicin.
For S. pneumoniae, 20 of 48 (42.7%) were resistant to
penicillin by oxacillin screening and one (2.1%) was resistant
to cefotaxime. MIC's for penicillin were determined for 18
isolates, of which 7 (38.9%) were fully sensitive (MIC
0.06 g/ml), 9 (50%) had intermediate resistance (MIC
0.12 1 g/ml) and 2 (11.1%) had high level resistance
(MIC 2 g/ml). Sixteen of 32 (50%) Enterobacteriaceae
produced extended-spectrum beta-lactamase (ESBL), thus
resistant to third generation cephalosporins. Eighteen
(56%) were resistant to gentamicin and 5 (15.6%) to
On TMP-SMX at baseline
10 subjects had 2 organisms and 2 had 3 organisms isolated from a NP swab.
M. catarrhalis n 22; H. influenzae n 26
TMP-SMX exposure: More than 1 organism per subject
Organisms not included Coagulase negative staphylococcus 10; Streptococcus viridans 2; other commensals 11; no growth 10;
# p = 0.0104 (Fisher's Exact 2-tail test)
p = 0.048 (Fisher's Exact 2-tail test)
The influence of baseline status of TMP-SMX on resistance
is shown in Table 5. Baseline levels of resistance to
TMPSMX were high, regardless of status but there was a trend
for higher resistance to TMP-SMX in subjects receiving it at
baseline (p = 0.065). MRSA was significantly associated
with baseline TMP-SMX (87% of subjects; p = 0.002) even
though baseline resistance in those never having received
TMP-SMX was also high (70%).
In subjects without a history of previous or current
hospitalization, antibiotic resistance in the most common
organisms isolated was not reduced. Unexpectedly, for S.
pneumoniae, TMP-SMX resistance was significantly more
common in subjects without a history of hospitalization.
Bacteremias are shown in Table 7. Nineteen subjects
(9.4%) had 23 episodes of bacteremia. Four had two
episodes and three had two pathogens from a single blood
culture. The bacteremias occurred a median of 30.3 (IQ:
4.6 36.6) weeks post enrolment. Only one subject had
bacteremia prior to enrolment (3 days). Enterobacteriacae
were the most commonly isolated group. More than 50%
produced ESBL and were also resistant to gentamicin,
showing a similar profile to NP isolates. Reduced
susceptibility to penicillin occurred in 3 of 4 S. pneumoniae
Three of four subjects with the same organism isolated
from nasopharynx and blood had identical resistance
patterns. One had ESBL-producing and gentamicin-resistant
K. pneumoniae. Another had Enterobacter, sensitive to 3rd
generation cephalosporins and gentamicin and a third
had S. pneumoniae with intermediate resistance to
penicillin. The fourth subject had MRSA in the nasopharynx but
no sensitivity information for the blood culture isolate.
Resistant to TMP-SMX
Resistance to selected antibiotics
Pen 20 (41.7%)# CTX 1 (2.1%)
Clox cloxacillin, Gent gentamicin, Amik amikacin, Pen penicillin; CTX cefotaxime; Amp ampicillin, Amox/clav amoxicillin-clavulanate
# S. pneumoniae MIC performed in 18 isolates: 7 (38.9%) fully sensitive (MIC 0.06 g/ml) 9 (50%) with intermediate resistance (MIC 0.12 1 g/
ml) and 2 (11.1%) with high level resistance (MIC 2 mg/ml) to penicillin
M. catarrhalis: 11 isolates tested for MIC; 14 of 17 isolates tested for beta-lactamase production. No significant differences for resistance to
penicillin, cloxacillin, cefotaxime, gentamicin, amikacin and TMP-SMX by present or previous exposure to TMP-SMX
Odds ratio (95% CI)
Multivariate logistic regression
Our study confirms a high carriage of potential
pathogens, many of which are antibiotic resistant, from NP and
blood culture isolates in HIV-infected children. The
majority of organisms from both NP and blood were
resistant to TMP-SMX and other antibiotics commonly
used for community-acquired infection. A disturbing
finding was the high prevalence of MRSA and
ESBL-producing Enterobacteriaceae from both sites.
The demographic features of HIV-infected children are
similar to those described previously at the Tygerberg
Family clinic where the majority were under two years of
age, had moderate or severe immunosuppression and
symptomatic HIV disease . Mortality has been
described elsewhere and was not analyzed further as it
may have been affected by multiple factors beyond the
scope of this report . The significant difference in age
of subjects stratified by TMP-SMX exposure probably
reflects utilization of the public health service. Subjects
entered the study from January 2003, as the Vertical
Total isolates tested
Not on TMP-SMX at
baseline Resistance (%)
On TMP-SMX at baseline
SMX Resistance (%)
No current or previous hospitalization (% organisms)
Antibiotic resistance (% tested for selected antibiotic)
Fisher's Exact 2-tail test
mission Prevention program was gradually being
introduced in the Western Cape. Consequently, many of the
older infants and children were only identified through
knowledge of their parents' HIV status, or when
presenting with clinical disease suggestive of HIV. Those never
exposed to TMP-SMX were significantly younger than
those already on TMP-SMX. Those previously on the drug
but not receiving it at baseline were older, possibly
reflecting poor retention in the public health system.
Colonization by S. pneumoniae, H. influenzae and M.
catarrhalis is well documented in early childhood .
Approximately 50% of children carry S. pneumoniae at two
years of age, declining to 20% by 7 years. Below 7 years of
age 40% of immunocompetent children in developed
countries carry M. catarrhalis and 30% H. influenzae .
Socioeconomic factors such as housing, overcrowding,
poor hygiene, access to health care and daycare are major
determinants of colonization. For example, in Australia,
Aboriginal children are colonized with M. catarrhalis, H.
influenzae and S. pneumoniae by 20 days of age, whereas
non-Aboriginal children acquire these organisms after
200 days of age . Increased numbers of colonizing
faecal organisms such as Enterobacteriaceae and
Pseudomonas have been found in malnourished infants and
children from resource-poor settings in the pre-HIV era
[7,8]. A recent comparative community-based study of
Cloxacillin 4 (80%)
TMP-SMX 5 (100%)
Penicillin 7 (58.3%)
TMP-SMX 8 (66.7%)
Cefotaxime 3 (50%)
Gentamicin 6 (50%)
TMP-SMX 6 (83.3%)
children aged between 4 months and 5 years, showed
more frequent carriage of Gram-negative enteric
pathogens in Brazilian (50%) and Angolan (57%) than Dutch
children (4%) .
Studies on NP S. pneumoniae in HIV-infected adults and
children from developed countries showed similar
carriage rates to uninfected subjects [27,3,28]. In Kenya,
Rusen et al found no increased NP S. pneumoniae
colonization in asymptomatic HIV-infected infants (20%)
compared to seronegative controls (22%) .
In our study, colonization by Enterobacteriaceae was
associated with age below a year and advanced HIV disease. S.
aureus was linked to CD4 depletion and Gram-negative
respiratory organisms to absence of CD4 depletion. High
carriage rates of S. aureus and possible relationship with
invasive disease, has been noted in HIV-infected adults
[29,30]. In a study from the Western Cape, comparing
community acquired pneumonia in HIV-infected and
uninfected infants, Zar et al found a higher rate of S. aureus
in nasopharyngeal aspirates and invasive disease, linking
this finding to TMP-SMX prophylaxis in HIV-positive
children . Similarly, in a recent survey of children
hospitalized with severe pneumonia in Kwazulu-Natal, South
Africa, HIV-infected children were significantly more
Number Resistant to TMP-SMX Resistance to selected antibiotics
*No data for one isolate
Two isolates had no data for for cefotaxime, gentamicin and TMP-SMX; Three had no data for amikacin
Clox cloxacillin; Gent gentamicin; Amik amikacin; Pen penicillin; Amp ampicillin; CTX cefotaxime; PTZ piperacillin/tazobactam; Mero
likely to be colonized with S. aureus (31%) than
HIVuninfected children (13.8%) .
TMP-SMX resistance occurs commonly in children. For
example in a recent survey of H. influenzae colonization in
daycare attendees in Brazil, 46% were resistant to
TMPSMX and 10% had multidrug resistance . Although
not reported, HIV prevalence was likely to be extremely
low. Abdel-Haq showed that both young age and
TMPSMX prophylaxis were risk factors for NP colonization
with multiply resistant S. pneumoniae in
immunocompromised and immunocompetent children from Detroit,
Antibiotic resistance was extremely common in our study.
Between 80 90% of most pathogens (except for M
catarrhalis) were resistant to TMP-SMX. Almost 80% of S.
aureus were methicillin-resistant and 50% of
Enterobacteriaceae had ESBL production. The majority of children
had advanced disease and frequent contact with both
inand outpatient hospital facilities. High prevalence of
antibiotic resistance has already been described in
malnourished children with pneumonia and also in children with
hospital-associated bacterial infection [32,33]. We did not
record TMP-SMX usage or frequency of healthcare
utilization in other family members, but speculate that both
were likely to be high, as other family members are also
likely to be HIV-infected. The children enrolled in the
study come from poor socio-economic conditions where
overcrowding and spread of antibiotic resistant pathogens
in homes are likely. As we did not link previous
hospitalization with antibiotic resistance in NP organisms, we
speculate that antibiotic resistance is well established in
homes of study subjects and possibly in the communities,
as well. As evidence of this, TMP-SMX resistance was
significantly higher in S. pneumoniae in subjects without a
history of hospitalization. Also, even though we found
significantly more MRSA in children on TMP-SMX at
baseline, 70% of those not on TMP-SMX also had MRSA,
supporting the contention that the organism is well
established in the homes of the infants. A major
limitation of our study is that we did not document NP
colonization in HIV-uninfected children from the same
communities or within the household of our subjects. We
plan to address these issues.
Colonization with antibiotic resistant organisms has been
noted in surveys of African children and adults. In 1997,
Woolfson described S. pneumoniae in 72% of 260
Zambian school children < 6 years of age. Antibacterial
resistance occurred in 34.1% of isolates; intermediate
resistance to penicillin occurred in 14.3% and to
TMPSMX in 12.7% . In the Kenyan study from 1997,
Rusen et al documented that 60% of S. pneumoniae
isolates had intermediate resistance to penicillin . Both
studies preceded the widespread use of TMP-SMX for
chemoprophylaxis in HIV-infected infants . MRSA has
been found more commonly in HIV-infected than
uninfected children in Kwazulu-Natal, South Africa .
The incidence of bacteremia (9.4%) is higher that from a
survey in the pre-HIV era. In a study of hospitalized
children at Tygerberg Hospital in 1989, 2% had bacteremia,
the most frequent isolates being S. pneumoniae and S.
aureus. In community-acquired infections, pathogens
were also sensitive to first line antibiotics . In a study
of infants with severe lower respiratory tract infection in
Soweto, S. pneumoniae and S. aureus from bacteremic
infants showed significantly higher levels of penicillin (54
versus 23%) and methicillin resistance (60% versus 0%)
respectively in HIV-infected than uninfected infants .
Community-associated infection due to MRSA is an
emerging problem in children from developed countries
[37,38]. In contrast, community-associated infection due
to ESBL-producing organisms is well documented in
adults, but not yet in children .
The colonizing NP flora and high level of antibiotic
resistance for Enterobacteriaceae and S. aureus suggest that
empiric antibiotic treatment should be adapted to cover
MRSA and ESBL-producing Enterobacteriaceae. Also,
amikacin is a more appropriate aminoglycoside than
gentamicin for severely ill HIV-infected children in our
region. A limitation of our study, however, is that we did
not distinguish between community and hospital
acquired bacteremia or nasopharyngeal colonization. To
our knowledge, this is the first documentation of
ESBLproducing Enterobacteriaceae causing bacteremia or
colonizing the nasopharynx in HIV-infected children.
The majority of HIV-infected children were colonized
with pathogenic organisms, with high levels of antibiotic
resistance. These included respiratory isolates such as S.
pneumoniae, H. influenzae and M. catarrhalis, and
gramnegative organisms such as Enterobacteriaceae and
Pseudomonas. The spectrum of antibiotic resistance in blood
culture isolates is similar to that found in the
nasopharynx. These findings have implications for empiric
antibiotic therapy in sick HIV-infected children. We recommend
antibiotics appropriate for ESBL-producing
Enterobacteriaceae and MRSA in severely ill HIV-infected children in
our setting. However, there is also concern that
widespread use of broader spectrum agents may lead to
resistance to these agents as well. There is an urgent need to
further document the spectrum and antibiotic resistance
profiles of HIV-infected children in under-resourced
The authors declare that they have no competing interests.
MC was the co-principal investigator of the original study
and contributed to the design of the present study. He
wrote the manuscript and conducted the analyses. EW
supervised the microbiology, assisted with original
analyses and gave intellectual input to the manuscript. JS
performed all the microbiological assays, and wrote the
initial draft of the manuscript. AW assisted with
bacteraemia data and gave intellectual input to the manuscript.
HZ co-designed the original study and the present study.
She gave intellectual input to the manuscript and
analyses. JS was awarded a M. Med degree at Stellenbosch
University for work in this study.
The Rockefeller Foundation funded the study. We thank Dr Carl Lombard,
MRC for reviewing the statistical methods. Prof. Lynne Liebowitz, Faculty
of Health Sciences, Stellenbosch University contributed to study design.
We thank Prof Shabir Madhi, Respiratory and Meningeal Pathogens
Research Unit, University of Witwatersrand and Dr. Colleen Bamford,
Department of Medical Microbiology, Tygerberg Academic Hospital for
reviewing the manuscript. Wessel Kleynhans and Judith Beukes of the
NHLS laboratories, Tygerberg Academic Hospital provided clinical
Study team: P Apolles, N Dlaku, E Dobbels, T Fakir, C Ford, D Gray, M
George, L Holt, T Jennings, A Joachim, J Karpakis, B Leibbrandt, A Loggie,
G Lottering, M Louw, I Mong, P Mtiya, D Nchuna, F Ngcokovana, V
Nkondlala, K Orpen, H Rabie, HS Schaaf, H Smit, S Strauss, R Streicher, E
Swanepoel, E Walters, MA Wolff.