Surveillance of Bloodstream Infections in Malawi

In this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to QECH, Blantyre, Malawi between 1998 and 2016.
The Malawi-Liverpool-Wellcome Trust Clinical Research Programme has provided routine, quality controlled, diagnostic blood culture service for febrile adult and paediatric medical patients admitted to QECH since 1998. A recommended 7–10 mL of blood were taken for culture under aseptic conditions from all adult patients admitted to the hospital with fever (axillary temperature >37·5°C) or clinical suspicion of sepsis, severe sepsis, or septic shock.²⁹ (link) Sepsis, severe sepsis, or septic shock were suspected in patients with tachycardia (≥90 beats per minute), hypotension (systolic blood pressure <90 mm Hg), tachypnoea (respiratory rate >20 per minute), or delirium. 3–10 mL of blood was taken from children with non-focal febrile illness who tested negative for malaria, who were severely ill with suspected sepsis, or who failed initial malaria treatment and remained febrile.¹⁸ (link) In this busy hospital, afebrile patients were unlikely to have blood sampled for culture unless critically ill with suspected sepsis. If patients were critically ill and sample for culture was taken, the patients were not excluded from analysis.
Since 2000, blood was inoculated into a single aerobic bottle using the automated BacT/ALERT system (bioMérieux, France)⁶ (link) before which, manual culture was used.³⁰ (link) Enterobacteriaceae and oxidase-positive Gram-negative bacilli were identified by API (BioMérieux, France), staphylococci by tube coagulase, β-haemolytic streptococci by Lancefield antigen testing, and salmonella by serotyping according to the White-Kauffmann-Le Minor scheme by the polyvalent O & H, O4, O9, Hd, Hg, Hi, Hm, and Vi antisera (Pro-Lab Diagnostics, UK). The identification of a sample of isolates as Salmonella enterica serotype Typhimurium was subsequently substantiated by whole genome sequencing and multi-locus sequence typing. Haemophilus influenzae was typed using type B antisera. Bacteria that form part of the normal skin or oral flora, including diphtheroids, bacilli, micrococci, coagulase-negative staphylococci, and α-haemolytic streptococci (other than S pneumoniae), were considered to be contaminants.³¹
Antimicrobial susceptibility tests were done by the disc diffusion method following the British Society of Antimicrobial Chemotherapy (BSAC) methods and breakpoints. Testing was in most cases limited to one plate containing six discs, and the choice of agent varied depending on the range of antimicrobials available to clinicians. Standard operating procedures are included in the appendix. Bacteria were defined as being resistant to Malawian first-line drugs (hereafter, RFL) if they were resistant to the three first-line antimicrobials commonly used in Malawi: amoxicillin, co-trimoxazole, and chloramphenicol for Gram-negative isolates; or penicillin, co-trimoxazole, and chloramphenicol for Gram-positive isolates. Isolates were considered multidrug resistant if they were resistant to three or more classes of antimicrobials to which reference strains are susceptible.³² (link) Gram-negative isolates have been screened for ESBL-producing status using a cefpodoxime disc since 2007. Before then, ESBL was inferred on the basis of resistance to ceftriaxone. Meticillin resistance in S aureus was inferred by cefoxitin resistance, which replaced oxacillin resistance testing in 2010.