We conducted a large, cross-sectional microbiologic study of patients with presumed infections seen at a large medical centre in Malawi. We observed that the common bacterial causes of bacteraemia differ between children and adults, and that S. aureus is extremely common in blood, abscesses, joints, and bone. We also observed widespread antimicrobial resistance to commonly used antibiotics.
Our findings highlight the variation in bacteremia etiology, both geographically and temporally, within sub-Saharan Africa [8, 12, 13]. In our setting, gram positive bacteria, especially S. aureus and S. pneumoniae, were the most common cause of bacteraemia and infections of other anatomic sites. An earlier study in neonates in Malawi observed a predominance of Salmonella and other gram negative bacilli in patients with bacteremia . We also isolated S. aureus more commonly than was observed elsewhere [7, 14]. However, in The Gambia, S. aureus and S. pneumoniae caused almost three quarters of bacteraemia cases in an urban hospital . In addition, this is a population which did not receive the pneumococcal conjugate vaccine.
Our observation that S. aureus was the most commonly isolated organism must be interpreted cautiously. Robust organisms, such as S. aureus and Salmonella, are more likely to be isolated than fastidious ones . Thus, the prevalence of the robust organisms could possibly be biased upwards. However, we frequently isolated S. pneumoniae, a less robust organism, which suggests that our aerobic culture techniques were adequate.
Although we had relatively few CSF cultures, the results were highly informative. C. neoformans was a common cause of meningitis, second only to S. pneumoniae. The high prevalence of Cryptococcus was most likely due to a high prevalence of HIV infection in the patient population at KCH, where up to three-quarters of medical inpatients are HIV infected. We can not comment on the frequency of tuberculous meningitis since culture for that organism was not attempted in this study population. We also observed very few cases of Haemophilus influenzae meningitis or bacteraemia, possibly due to the introduction of routine childhood H. influenzae b vaccination in 2002. Neisseria meningitidis also was not recovered reflecting this as a rare cause of meningitis in this population.
We found widespread bacterial resistance to almost all of our commonly used antibiotics. Our findings contrast starkly with the limited resistance observed in Malawi between 1996 and 2001, although resistance to first line antibiotics for bacteremia was observed over a decade ago [6, 12]. Of particular concern is high incidence of bacteraemia caused by non-Typhi Salmonella, which has increased with development of multi-drug resistance . In our setting, Salmonella is a common gram negative bacterium infecting blood and joints and it was susceptible to gentamicin and ceftriaxone in vitro. The problem of fluoroquinolone resistance in Salmonella enterica serotypes other than Typhi is not well studied in Africa.
In a separate Malawi study, no fluoroquinolone resistance was reported among Salmonella isolates . In a study from Senegal, approximately 5% of isolates showed low level fluoroquinolone resistance . We found none of the 25 Salmonella isolates tested to be nalixidic acid resistant although interestingly close to half (11/25) were nalidixic acid intermediate (Table 3). A previous study suggests Salmonella strains with intermediate susceptibility by disk diffusion may have MICs in a range consistent with low level ciprofloxacin resistance . Unfortunately ciprofloxacin MICs were not available to determine if these nalidixic acid intermediate isolates did, in fact, have low level ciprofloxacin resistance. This issue deserves close scrutiny in the coming years.
Our findings of widespread antimicrobial resistance have a strong bearing on the current treatment choices. Malawi, like most resource poor countries, does not provide routine microbiologic culture and sensitivity testing . Instead, the Malawi National Treatment Guidelines provides for initiation of antimicrobial therapy empirically, based on clinical observation and history, which is often broad spectrum [16, 20–23]. However, the development of antimicrobial resistance in this context can have major clinical consequences. In Tanzania, antimicrobial resistance was a significant risk for death in children with bacteremia . Antimicrobial resistance can also lead to treatment failures, prolonged drug treatment courses and protracted hospital admissions .
Considering the potential consequences of increased antimicrobial resistance, our findings support a review of the current antibiotic choices in Malawi. Of the antibiotics we examined, only three are not widely used and show good susceptibility. Ceftriaxone and ciprofloxacin retain activity against gram negative bacteria, including Salmonella spp. Gram positive organisms, including S. aureus and S. pneumoniae, remain susceptible to clindamycin, and may also be susceptible to third-generation cephalosporins. Revision of the national treatment guidelines with inclusion of clindamycin, and ciprofloxacin or ceftriaxone, coupled with promotion of their prudent use, should improve patient outcomes and potentially save costs of providing clinical services.
This study represents an account of community-acquired infections in that it included only specimens collected at admission, and did not include subsequent specimens and specimens from patients who had already been on antimicrobial therapy prior to presentation. Unfortunately, we were unable to include patients who presented to the hospital outside of the daytime hours, due to the constraints of study personnel. In addition, the maternity ward was located outside the main hospital campus, limiting the enrolment of patients there. Thus, our study population was not a complete assessment of all infections presenting to KCH during the study period. Also clinical outcomes were not collected to triangulate our laboratory findings. More advanced microbiologic testing such as minimum inhibitory concentration (MIC) and extended spectrum beta-lactamases (ESBLs), which would have helped refine some of our basic findings, were not performed. Nonetheless, we were able to enrol a large number of patients with a diverse spectrum of clinical syndromes and also perform basic identification and antimicrobial susceptibility testing. Consequently, our results provide a large microbiologic assessment of bacterial infections in Malawi.
The widespread antimicrobial resistance in our study is concerning. Choices for empirical therapy in Malawi should be revised accordingly. Newer antibiotics, though more costly, must be used more widely, but judiciously, to limit the further spread of antimicrobial resistance. The establishment of a dependable, accurate and timely microbiological service and surveillance system along with optimal use of this service by the clinicians should considerably improve the care of patients. Finally, prudent use of antimicrobials should be promoted.