Predictors of time to recovery in infants with probable serious bacterial infection

Prashant Singh, Nitya Wadhwa, Rakesh Lodha, Halvor Sommerfelt, Satinder Aneja, Uma Chandra Mouli Natchu, Jagdish Chandra, Bimbadhar Rath, Vinod Kumar Sharma, Mohini Kumari, Savita Saini, Sushil Kumar Kabra, Shinjini Bhatnagar, Tor A Strand, Prashant Singh, Nitya Wadhwa, Rakesh Lodha, Halvor Sommerfelt, Satinder Aneja, Uma Chandra Mouli Natchu, Jagdish Chandra, Bimbadhar Rath, Vinod Kumar Sharma, Mohini Kumari, Savita Saini, Sushil Kumar Kabra, Shinjini Bhatnagar, Tor A Strand

Abstract

Introduction: Serious bacterial infections continue to be an important cause of death and illness among infants in developing countries. Time to recovery could be considered a surrogate marker of severity of the infection. We therefore aimed to identify clinical and laboratory predictors of time to recovery in infants with probable serious bacterial infection (PSBI).

Methods: We used the dataset of 700 infants (7-120 days) enrolled in a randomised controlled trial in India in which 10mg of oral zinc or placebo was given to infants with PSBI. PSBI was defined as signs/symptoms of possible serious bacterial infection along with baseline C-reactive protein(CRP) level >12mg/L. Time to recovery was defined as time from enrolment to the end of a 2-day period with no symptoms/signs of PSBI and daily weight gain of at least 10g over 2 succesive days on exclusive oral feeding. Cox proportional hazard regression was used to measure the associations between relevant variables and time to recovery.

Results: Infants who were formula fed prior to illness episode had 33% longer time to recovery (HR-0.67, 95%CI-0.52, 0.87) than those who were not. Being underweight (HR-0.84, 95%CI-0.70, 0.99), lethargic (HR-0.77, 95%CI-0.62, 0.96) and irritable (HR-0.81, 95%CI-0.66, 0.99) were independent predictors of time to recovery. Baseline CRP was significantly associated with time to recovery (P<0.001), higher CRP was associated with longer time to recovery and this association was nearly linear.

Conclusion: Simple clinical and laboratory parameters such as formula feeding prior to the illness, being underweight, lethargic, irritable and having elevated CRP levels could be used for early identification of infants with PSBI at risk for protracted illness and could guide prompt referral to higher centers in resource limited settings. This also provides prognostic information to clinicians and family as longer recovery time has economic and social implications on the family in our setting.

Trial registration: ClinicalTrials.gov NCT00347386.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Correlation between baseline CRP level…
Fig 1. Correlation between baseline CRP level and time to recovery (in hours).
Several studies in the past have used cutoffs in the range of CRP concentrations of 40 mg/L to differentiate between bacterial and non-bacterial or viral infections. [11,12]. We therefore also performed an additional analysis where we dichotomized serum CRP concentration with a cut-off of 40 mg/L. In this analysis we found that predictors for time to recovery from PSBI remained the same and infants with CRP ≥ 40 mg/L were found to have on an average 33% longer time to recovery than those with values below that.

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