BACKGROUND
In low-resource settings, limited laboratory capacity adds to the burden of central nervous system (CNS) infections in children and spurs overuse of antibiotics. The commercially available BioFire® FilmArray® Meningitis/Encephalitis Panel (FA-ME) with its capability to simultaneously detect 14 pathogens in cerebrospinal fluid (CSF), could potentially narrow such a diagnostic gap.
METHODS
In Mbarara, Uganda, we compared clinical utility (clinical turnaround time [cTAT], microbial yield, and influence on patient outcome and antibiotic exposure) of FA-ME with bacterial culture, in children 0–12 years with suspected CNS infection.
RESULTS
Of 212 enrolled children, CSF was sampled from 194. All samples underwent bacterial culture, of which 193 also underwent FA-ME analyses. FA-ME analyses prospectively influenced care for 169 of the 193 patients, and they constituted an ‘Index group’. The remaining 43/212 patients constituted a ‘Reference group’. Of all 194 CSF-sampled patients, 87% (168) had received antibiotics before lumbar puncture. Median cTAT for FA-ME was 4.2 h, vs. two days for culture. Bacterial yield was 12% (24/193) and 1.5% (3/194) for FA-ME and culture, respectively. FA-ME viral yield was 12% (23/193). Fatality rate was 14% in the Index group vs. 19% in the Reference group (P = 0.20). From clinician receival of FA-ME results, median antibiotic exposure was 6 days for bacteria-negative vs. 13 days for bacteria-positive patients (P = 0.03). Median hospitalization duration was 7 vs. 12 days for FA-ME negative and positive patients, respectively (P < 0.01).
CONCLUSIONS
In this setting, clinical FA-ME utility was found in a higher and faster microbial yield and shortened hospitalization and antibiotic exposure of patients without CSF pathology. More epidemiologically customized pathogen panels may increase FA-ME utility locally, although its use in similar settings would require major cost reductions.
BACKGROUND
Circulating markers of immune and endothelial activation risk stratify infection syndromes agnostic to disease aetiology. However, their utility in children presenting from the community remains unclear.
METHODS
This study recruited children aged 1-59 months presenting with community-acquired acute febrile illnesses to seven hospitals in Bangladesh, Cambodia, Indonesia, Laos, and Viet Nam. Clinical parameters and biomarker concentrations were measured at presentation. The outcome measure was death or receipt of vital organ support within two days of enrolment. Prognostic performance of endothelial (Ang-1, Ang-2, sFlt-1) and immune (CHI3L1, CRP, IP-10, IL-1ra, IL-6, IL-8, IL-10, PCT, sTNFR-1, sTREM-1, suPAR) activation markers, WHO Danger Signs, and two validated severity scores (LqSOFA, SIRS) was compared.
RESULTS
3,423 participants were recruited. 133 met the outcome (weighted prevalence: 0.34%; 95% CI 0.28-0.41). sTREM-1 exhibited highest prognostic accuracy (AUC 0.86; 95% CI 0.82-0.90), outperforming WHO Danger Signs (AUC 0.75; 95% CI 0.70-0.80; p < 0.001), LqSOFA (AUC 0.74; 95% CI 0.70-0.78; p < 0.001), and SIRS (AUC 0.63; 95% CI 0.58-0.68; p < 0.001). Discrimination of immune and endothelial activation markers was particularly strong for children who deteriorated later in the course of their illness. Compared to WHO Danger Signs, an sTREM-1-based triage strategy improved recognition of children at risk of progression to life-threatening infection (sensitivity: 0.80 vs. 0.72), while maintaining comparable specificity (0.81 vs. 0.79).
CONCLUSIONS
Measuring circulating markers of immune and endothelial activation may help earlier recognition of febrile children at risk of poor outcomes in resource-constrained community settings.
To determine whether adding urine culture to urinary tract infection diagnosis in pregnant women from refugee camps in Lebanon reduced unnecessary antibiotic use.
METHODS
We conducted a prospective, cross-sectional study between April and June 2022 involving pregnant women attending a Médecins Sans Frontières sexual reproductive health clinic in south Beirut. Women with two positive urine dipstick tests (i.e. a suspected urinary tract infection) provided urine samples for culture. Bacterial identification and antimicrobial sensitivity testing were conducted following European Committee on Antimicrobial Susceptibility Testing guidelines. We compared the characteristics of women with positive and negative urine culture findings and we calculated the proportion of antibiotics overprescribed or inappropriately used. We also estimated the cost of adding urine culture to the diagnostic algorithm.
FINDINGS
The study included 449 pregnant women with suspected urinary tract infections: 18.0% (81/449) had positive urine culture findings. If antibiotics were administered following urine dipstick results alone, 368 women would have received antibiotics unnecessarily: an overprescription rate of 82% (368/449). If administration was based on urine culture findings plus urinary tract infection symptoms, 144 of 368 women with negative urine culture findings would have received antibiotics unnecessarily: an overprescription rate of 39.1% (144/368). The additional cost of urine culture was 0.48 euros per woman.
CONCLUSION
A high proportion of pregnant women with suspected urinary tract infections from refugee camps unnecessarily received antibiotics. Including urine culture in diagnosis, which is affordable in Lebanon, would greatly reduce antibiotic overprescription. Similar approaches could be adopted in other regions where microbiology laboratories are accessible.
Whole genome sequencing (WGS) of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger.
METHODS
Stools of 383 healthy participants were collected among which 92.4% were ESBL-Enterobacterales carriers. A subset of 90 ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads.
RESULTS
Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The blaCTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, blaCTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of blaCTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.
CONCLUSIONS
Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of blaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.
Patients with advanced HIV disease (AHD), defined as WHO clinical stage 3 or 4 and/or CD4<200, have a high risk of death. One common cause of death is invasive bacterial infection (IBI, i.e., septicemia or meningitis). The global increase of antibiotic resistance threatens current treatments against bacterial infections. This study aims to describe the burden of IBI among patients with AHD to guide empirical treatment protocols.
METHODS
This is a prospective, descriptive study implemented at Kabinda General Hospital in Kinshasa, Democratic Republic of Congo (DRC). All patients with AHD and a blood or cerebrospinal fluid (CSF) culture collected because of: 1) fever/hypothermia and/or signs of shock, on admission or during hospitalization, and/or 2) previous exposure to care (<30 days), were eligible to participate. Clinical and bacteriological data were collected. An IBI was defined as a positive blood or CSF culture, and then categorized as: 1) community-acquired or healthcare-associated, if occurring =48 hours since hospitalization, and contingent on previous exposure to care (<30 days), or 2) hospital-acquired, if occurring >48 hours after hospitalization.
RESULTS
From August 2021 to July 2022, we included 997 patients, corresponding to 1198 hospitalizations with =1 blood and/or CSF culture. The proportions of community-acquired, healthcare-associated, and hospital-acquired IBI among hospitalizations were 5.9% (71/1198), 9.2% (110/1198), and 3.5% (42/1198), respectively. The main bacterial agents responsible for community-acquired and healthcare-associated IBI were non-Typhi Salmonella followed by Gram-positive Cocci, while K. pneumoniae was most common in hospital-acquired IBI. The levels of antibiotic susceptibility among Enterobacterales were similar between community-acquired and healthcare-associated IBI, with low susceptibility to ceftriaxone and ciprofloxacin, but high susceptibility to carbapenems and azithromycin.
CONCLUSION
We confirmed alarming levels of antibiotic resistance among patients with ADH in the DRC. Discussions are ongoing to translate results into practice, in particular to target broad spectrum empirical antibiotics.
KEY MESSAGE
Invasive bacterial infections among hospitalized patients with advanced HIV in Kinshasa showed high levels of antibiotic resistance regardless of their recent, previous exposure to care.
This abstract is not to be quoted for publication.