Alarming rates of antimicrobial resistance and fungal sepsis in outborn neonates in North India

Abstract

BackgroundThere is a paucity of data on the epidemiology of sepsis in outborn neonates being referred to level-3 units in low- and middle-income countries (LMIC). The objective of the present study was to evaluate the prevalence of sepsis and outcomes of outborn neonates with sepsis, and to characterize the pathogen profile and antimicrobial resistance (AMR) patterns of common isolates in them.MethodsIn this prospective observational cohort study (2011–2015), a dedicated research team enrolled all neonates admitted to an outborn level-3 neonatal unit and followed them until discharge/death. Sepsis work-up including blood culture(s) was performed upon suspicion of sepsis. All the isolates were identified and tested for antimicrobial susceptibility. Gram-negative pathogens resistant to any three of the five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) were labeled multi-drug resistant.ResultsOf the total of 2588 neonates enrolled, culture positive sepsis and total sepsis–i.e. culture positive and/or culture negative sepsis–was diagnosed in 13.1% (95% CI 11.8% to 14.5%) and 54.7% (95% CI 52.8% to 56.6%), respectively. The case fatality rates were 23.4% and 11.0% in culture-positive and total sepsis, respectively. Sepsis accounted for two-thirds of total neonatal deaths (153/235, 63.0%). Bacterial isolates caused about three-fourths (296/401; 73.8%) of the infections. The two common pathogens–Klebsiella pneumoniae (n = 50, 12.5%) and Acinetobacter baumannii (n = 46, 11.5%)–showed high degree of multi-drug resistance (78.0% and 91.3%, respectively) and carbapenem resistance (84.0% and 91.3%, respectively). About a quarter of infections were caused by Candida spp. (n = 91; 22.7%); almost three-fourths (73.7%) of these infections occurred in neonates born at or after 32 weeks’ gestation and about two-thirds (62.1%) in those weighing 1500 g or more at birth.ConclusionsIn this large outborn cohort, we report high burden of sepsis, high prevalence of systemic fungal infections, and alarming rates of antimicrobial resistance among bacterial pathogens.

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia

“…pneumoniae is among the most common cause of bloodstream infections (BSI) in South (S) and Southeast (SE) Asia [4][5][6] where it is associated with a high mortality rate [4,7]. Available data suggest a heterogenous landscape in terms of drug resistance; for example, CP strains are rare in SE Asia (< 1-4% [5,8,9]) but common in S Asia (28-70% [10,11]) and the prevalence of extendedspectrum beta-lactamase (ESBL, confers resistance to the third-generation cephalosporins) producing organisms varies from 12 to 79% in these regions [4-6, 8, 10]. Studies investigating ESBL and CP variants in S/SE Asia implicate CTX-M-15 as the most common ESBL type [12,13], while NDM and OXA-48-like enzymes are the most commonly described carbapenemases [11,[14][15][16].…”

Population Pharmacokinetics of Gentamicin in Neonates with Hypoxemic‐Ischemic Encephalopathy Receiving Controlled Hypothermia

“…Similarly, antimicrobial resistance is known to vary by geographic location, and it was demonstrated that 77% of the overall organisms isolated from two separate NICUs were multidrug resistant (MDR) with 83.4% of the gram‐negative organisms being MDR . Resistance also varies by the infecting organism(s), for example, rates as high as 91% of Acinetobacter baumannii isolates are MDR and a significant cause of mortality . Therefore, the reliance on the historical peak gentamicin range of 5–10 mg/L is probably not appropriate, especially when selecting empirical therapy, because the organism and MIC are not known when antimicrobial therapy is initiated.…”

“…34 Resistance also varies by the infecting organism(s), for example, rates as high as 91% of Acinetobacter baumannii isolates are MDR and a significant cause of mortality. [35][36][37] Therefore, the reliance on the historical peak gentamicin range of 5-10 mg/L is probably not appropriate, especially when selecting empirical therapy, because the organism and MIC are not known when antimicrobial therapy is initiated. As such, targeting a C max in the range of 10-12 mg/L with a C min level lower than 2 mg/L until the organism and MIC are known is prudent, considering these concentrations were associated with safety and efficacy.…”

Carbapenem-Resistant Gram-Negative Bacterial Infections in Children

“…Patients from countries where CRO are endemic (e.g., India, Turkey, or Egypt) (11)(12)(13)(14)25) may introduce CRO into pediatric institutions in countries where they are not endemic, suggesting the need for specific interventions, such as screening for colonization and specific empirical antimicrobial treatment in patients from these countries newly admitted with infectious diseases (36,40,42).…”