ABSTRACT
Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.
Subject(s)
Acinetobacter baumannii , Anti-Bacterial Agents , Gram-Negative Bacteria , Gram-Negative Bacterial Infections , Klebsiella pneumoniae , Microbial Sensitivity Tests , Neonatal Sepsis , Humans , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Neonatal Sepsis/microbiology , Neonatal Sepsis/drug therapy , Infant, Newborn , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/genetics , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/microbiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/isolation & purification , Acinetobacter baumannii/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Klebsiella pneumoniae/genetics , Amikacin/pharmacology , Amikacin/therapeutic use , Fosfomycin/pharmacology , Fosfomycin/therapeutic use , beta-Lactamases/genetics , beta-Lactamases/metabolism , Escherichia coli/drug effects , Escherichia coli/genetics , Escherichia coli/isolation & purification , Developing Countries , Drug Resistance, Multiple, Bacterial/genetics , Drug Therapy, Combination , Serratia marcescens/drug effects , Serratia marcescens/genetics , Serratia marcescens/isolation & purification , Enterobacter cloacae/drug effects , Enterobacter cloacae/genetics , Enterobacter cloacae/isolation & purification , Bacterial Proteins/genetics , Bacterial Proteins/metabolismABSTRACT
One third of patients were colonized by Candida auris during a point-prevalence survey in a neonatal unit during an outbreak in South Africa. The sensitivity of a direct PCR for rapid colonization detection was 44% compared with culture. The infection incidence rate decreased by 85% after the survey and implementation of isolation/cohorting.
Subject(s)
Candida auris , Disease Outbreaks , Infant, Newborn , Humans , Prevalence , South Africa/epidemiology , Polymerase Chain ReactionABSTRACT
BACKGROUND: Rapid diagnosis of drug-resistant Mycobacterium tuberculosis is a challenge in low-income countries. Phenotypic drug susceptibility testing using Sensititre® MycoTB assay and the resazurin microtitre plate assay (REMA) are relatively new innovative methods to determine drug susceptibility. OBJECTIVES: This study aimed to determine the performance of the Sensititre and REMA for M. tuberculosis drug susceptibility testing in a high-volume tuberculosis reference laboratory. METHODS: A laboratory-based study was performed at the Inkosi Albert Luthuli Central Hospital Tuberculosis Laboratory from January 2014 to June 2015. The Sensititre® MycoTB plate and REMA were compared to the gold standard agar proportion method (APM) using 134 stored isolates. RESULTS: Agreement between the Sensititre® MycoTB plate and APM was observed with 98% sensitivity, 82% specificity, 94% positive and 93% negative predictive values of the Sensititre® MycoTB assay for the detection of rifampicin resistance and 97%, 96%, 99% and 88% for isoniazid resistance. Good categorical agreement between the REMA and the APM was observed among isolates with 89% sensitivity, 68% specificity, 89% positive and 68% negative predictive value for the detection of rifampicin resistance and 95%, 96%, 99% and 81% for isoniazid resistance. Results for the second-line drugs showed elevated minimum inhibitory concentrations for multidrug-resistant and extensively drug-resistant tuberculosis isolates. CONCLUSION: The REMA and Sensititre® MycoTB plate are attractive alternatives to the gold standard APM for the phenotypic detection of M. tuberculosis drug resistance.
ABSTRACT
South Africa is experiencing a widespread drug-resistant tuberculosis epidemic, although data are limited regarding the current situation. This study finds that the extensively drug-resistant tuberculosis (XDR-TB) incidence in KwaZulu-Natal increased to 3.5 cases/100,000 (776 cases) in 2011-2012. XDR-TB cases are widely distributed geographically, with the majority of districts experiencing a rise in incidence.
