Time to positivity of blood cultures in a level IV NICU varies based on organism category and population subgroups: is a 36-hour rule out safe?

BACKGROUND: Time to positivity (TTP) of blood cultures and organism characteristics may be different in a Level IV NICU population. METHODS: Retrospective study of 309 Level IV NICU positive blood cultures between January 2012 to December 2018 describing TTP and organism characteristics. RESULTS: Median TTP [IQR] was 21.1 [14.3, 25.2] hours, with 91.2% positive at 36 h, and 96.1% positive at 48 h. Gram negative definite pathogens had the shortest TTP (13.0 [11.4, 15.4] hours) compared to gram positive definite pathogens (16.3 [13.0, 22.4] hours). TTP for treated gram positive commensal organisms (22.3 [20.1, 30.4] hours) and those considered contaminants (23.6 [21.4, 26.0] hours), was significantly longer than both gram positive and negative definite pathogens. CONCLUSION: When antimicrobials are initiated due to concern for bacteremia and blood cultures have not identified a causative pathogen at 36 h, antimicrobials may be safely discontinued in the majority of Level IV NICU patients.

Pan-GWAS of Streptococcus agalactiae Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation.

Streptococcus agalactiae (group B streptococcus; GBS) is a colonizer of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterized by clonal complexes (CCs) with different invasive potentials. CC17, for example, is a hypervirulent lineage commonly associated with neonatal sepsis and meningitis, while CC1 is less invasive in neonates and more commonly causes invasive disease in adults with comorbidities. The genetic basis of GBS virulence and the extent to which different CCs have adapted to different host environments remain uncertain. We have therefore applied a pan-genome-wide association study (GWAS) approach to 1,988 GBS strains isolated from different hosts and countries. Our analysis identified 279 CC-specific genes associated with virulence, disease, metabolism, and regulation of cellular mechanisms that may explain the differential virulence potential of particular CCs. In CC17 and CC23, for example, we have identified genes encoding pilus, quorum-sensing proteins, and proteins for the uptake of ions and micronutrients which are absent in less invasive lineages. Moreover, in CC17, carriage and disease strains were distinguished by the allelic variants of 21 of these CC-specific genes. Together our data highlight the lineage-specific basis of GBS niche adaptation and virulence.IMPORTANCE GBS is a leading cause of mortality in newborn babies in high- and low-income countries worldwide. Different strains of GBS are characterized by different degrees of virulence, where some are harmlessly carried by humans or animals and others are much more likely to cause disease.The genome sequences of almost 2,000 GBS samples isolated from both animals and humans in high- and low- income countries were analyzed using a pan-genome-wide association study approach. This allowed us to identify 279 genes which are associated with different lineages of GBS, characterized by a different virulence and preferred host. Additionally, we propose that the GBS now carried in humans may have first evolved in animals before expanding clonally once adapted to the human host.These findings are essential to help understand what is causing GBS disease and how the bacteria have evolved and are transmitted.

Challenges in reducing group B Streptococcus disease in African settings.

Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis in high-income settings and is associated with high rates of neonatal mortality and morbidity. There is now increasing evidence to suggest that there is a high GBS disease burden in resource-limited countries, and it is therefore critically important to identify suitable and practical preventive strategies. In Europe and North America, intrapartum antibiotic prophylaxis (IAP) has led to a dramatic reduction of early-onset GBS disease. However, the methods for identifying pregnant women who should receive IAP and how to reduce late-onset GBS disease are not without controversy and are challenging for most sub-Saharan African countries. GBS vaccines are approaching phase III trials but are still under development. This review aims to explore the current evidence related to strategies for reducing invasive GBS disease in an African setting, the development of a GBS vaccine and whether preventative measures against GBS disease can be practically implemented.

Early use of corticosteroids in infants with a clinical diagnosis of Pneumocystis jiroveci pneumonia in Malawi: a double-blind, randomised clinical trial.

BACKGROUND: Pneumocystis jiroveci pneumonia (PJP) is the most common opportunistic infection in infants with vertically acquired HIV infection and the most common cause of death in HIV-infected infants. OBJECTIVES: To determine whether early administration of adjuvant corticosteroids in addition to standard treatment reduces mortality in infants with vertically acquired HIV and clinically diagnosed PJP when co-infection with cytomegalovirus and other pathogens cannot be excluded. METHODS: A double-blind placebo-controlled trial of adjuvant prednisolone treatment in HIV-exposed infants aged 2-6 months admitted to Queen Elizabeth Central Hospital, Blantyre who were diagnosed clinically with PJP was performed. All recruited infants were HIV-exposed, and the HIV status of the infant was confirmed by DNA-PCR. HIV-exposed and infected infants as well as HIV-exposed but non-infected infants were included in the study. The protocol provided for the addition of prednisolone to the treatment at 48 h if there was clinical deterioration or an independent indication for corticosteroid therapy in any patient not receiving it. Oral trimethoprim-sulfamethoxazole (TMP/SMX) therapy and full supportive treatment were provided according to established guidelines. Primary outcomes for all patients included survival to hospital discharge and 6-month post-discharge survival. RESULTS: It was planned to enroll 200 patients but the trial was stopped early because of recruitment difficulties and a statistically significant result on interim analysis. Seventy-eight infants were enrolled between April 2012 and August 2014; 36 infants (46%) were randomised to receive corticosteroids plus standard treatment with TMP/SMX, and 42 infants (54%) received the standard treatment plus placebo. In an intention-to treat-analysis, the risk ratio of in-hospital mortality in the steroid group compared with the standard treatment plus placebo group was 0.53 [95% CI 0.29-0.97, p = 0.038]. The risk ratio of mortality at 6 months was 0.63 (95% CI 0.41-0.95, p = 0.029). Two children who received steroids developed bloody stools while in hospital. CONCLUSION: In infants with a clinical diagnosis of PJP, early use of steroids in addition to conventional TMP/SMX therapy significantly reduced mortality in hospital and 6 months after discharge.

Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB.

Faster elimination of drug tolerant 'persister' bacteria may shorten treatment of tuberculosis (TB) but no method exists to quantify persisters in clinical samples. We used automated image analysis to assess whether studying growth characteristics of individual Mycobacterium tuberculosis colonies from sputum on solid media during early TB treatment facilitates 'persister' phenotyping. As Time to Detection (TTD) in liquid culture inversely correlates with total bacterial load we also evaluated the relationship between individual colony growth parameters and TTD. Sputum from TB patients in Malawi was prepared for solid and liquid culture after 0, 2 and 4 weeks of treatment. Serial photography of agar plates was used to measure time to appearance (lag time) and radial growth rate for each colony. Mixed-effects modelling was used to analyse changing growth characteristics from serial samples. 20 patients had colony measurements recorded at ≥1 time-point. Overall lag time increased by 6.5 days between baseline and two weeks (p = 0.0001). Total colony count/ml showed typical biphasic elimination, but long lag time colonies (>20days) had slower, monophasic decline. TTD was associated with minimum lag time (time to appearance of first colony1). Slower elimination of long lag time colonies suggests that these may represent a persister subpopulation of bacilli.