Utilization of Blood Culture in South Asia for the Diagnosis and Treatment of Febrile Illness

Abstract

Background: Blood culture is the current standard for diagnosing bacteremic illnesses, yet it is not clear how physicians in many low- and middle-income countries utilize blood culture for diagnostic purposes and to inform treatment decisions.

Methods: We screened suspected enteric fever cases from 6 hospitals in Bangladesh, Nepal, and Pakistan, and enrolled patients if blood culture was prescribed by the treating physician. We used generalized additive regression models to analyze the probability of receiving blood culture by age, and linear regression models to analyze changes by month to the proportion of febrile cases prescribed a blood culture compared with the burden of febrile illness, stratified by hospital. We used logistic regression to analyze predictors for receiving antibiotics empirically. We descriptively reviewed changes in antibiotic therapy by susceptibility patterns and coverage, stratified by country.

Results: We screened 30 809 outpatients resulting in 1819 enteric fever cases; 1935 additional cases were enrolled from other hospital locations. Younger outpatients were less likely to receive a blood culture. The association between the number of febrile outpatients and the proportion prescribed blood culture varied by hospital. Antibiotics prescribed empirically were associated with severity and provisional diagnoses, but 31% (1147/3754) of enteric fever cases were not covered by initial therapy; this was highest in Pakistan (50%) as many isolates were resistant to cephalosporins, which were commonly prescribed empirically.

Conclusions: Understanding hospital-level communication between laboratories and physicians may improve patient care and timeliness of appropriate antibiotics, which is important considering the rise of antimicrobial resistance.

Keywords: South Asia; antimicrobial resistance; blood culture; fever; typhoid.

Figure 1.

Flow of data for analysis, Surveillance for Enteric Fever in Asia Project (SEAP)—Bangladesh, Nepal and Pakistan, April 2017–March 2019. Note: Full adherence = Attending physicians prescribed a blood culture for outpatients meeting the inclusion criteria (3 or more days of fever and residence within the hospital catchment area); Partial adherence = Attending physicians only prescribed a blood culture based on clinical suspicion among those meeting the inclusion criteria.

Figure 2.

Probability of receiving a prescription for blood culture, by age in years and site, (SEAP)—Partial adherence* hospitals in Bangladesh and Pakistan, April 2017–March 2019. *Hospitals where physicians prescribed a blood culture based only on clinical suspicion and did not fully adhere to the SEAP recruitment protocol of prescribing a blood culture to all patients with fever for 3 more days and residence within the hospital catchment area.

Figure 3.

Proportion of febrile outpatients prescribed a blood culture predicted by total number of febrile outpatients in the same month and 1–5 months ago, (SEAP)—Partial adherence* hospitals in Bangladesh and Pakistan, April 2017–March 2019. *Hospitals where physicians only prescribed a blood culture based on clinical suspicion and did not fully adhere to the SEAP recruitment protocol of advising a blood culture to all patients with fever for 3 or more days and residence within the hospital catchment area.

Figure 4.

Antibiotics classes prescribed before and after results available from blood culture, by blood culture status and hospital (SEAP)—Full adherence^‡ hospitals in Bangladesh and Nepal, April 2017–March 2019. ‡ Hospitals where physicians prescribed a blood culture to all patients with fever for 3 or more days and residence within the hospital catchment area, based on the SEAP recruitment protocol. †If no change in treatment, empiric prescription displayed. *Multiple antibiotics prescribed at given time point.

Figure 5.

Changes to treatment after results of blood culture and antimicrobial sensitivity testing among participants with Salmonella Typhi and Paratyphi A isolated, by country, (SEAP)—Bangladesh, Nepal and Pakistan, April 2017–March 2019. Note: This alluvial diagram depicts all enteric fever cases stratified by country and how treatment was modified based on blood culture results. The colors originate at the first stage, where patients were categorized based on their isolate’s susceptibility pattern to antibiotics prescribed empirically, if any. Based on the antibiotic, whether multiple antibiotics were prescribed empirically, and isolate susceptibility, the second stage stratifies patient as covered or not covered by initial therapy. The third stage depicts whether patients were prescribed additional antibiotics based on their initial therapy coverage, resulting in the fourth stage—whether a patient’s final treatment status with the hospital resulted in coverage.