Bacteriophages (phages) were discovered in the early part of the 20th century, and their ability to eliminate bacterial infections as bacterial viruses gathered interest almost immediately. Bacteriophage therapy was halted in the Western world due to inconclusive results in early experiments and the concurrent discovery of antibiotics. The spread of antibiotic-resistant bacteria has elicited renewed interest in bacteriophages as a natural alternative to conventional antibiotic therapy. Interest in the application of bacteriophages has also expanded to include the environment, such as wastewater treatment, agriculture and aquaculture. Although the complete phage is important in bacteriophage therapy, the focus is shifting to purified phage enzymes. These enzymes are an attractive option for pharmaceutical companies with their patent potential. They can be bio-engineered for enhanced adjuvant properties, such as a broadened spectrum of activity or binding capability. Enzymes also eliminate the concern that the prophage might integrate resistance genes into the bacterial genome. From a clinical perspective, the first randomised clinical controlled phage therapy trial was conducted with more pioneering phase I/II clinical studies on the horizon. In this opinion paper, the authors outline bacteriophages as naturally occurring bactericidal entities, their therapeutic potential against antibiotic-resistant bacteria and compare them to antibiotics. Their potential multipurpose application in the medical field is also addressed, including the use of bacteriophages for vaccination, and utilisation of the antimicrobial enzymes that they produce.
22 January 2022 in International Journal of Infectious Diseases
Outbreaks of community-acquired Pseudomonas aeruginosa are typically small and localized. We investigated an increase in community-acquired infections with P. aeruginosa in Cape Town, South Africa. Cases were defined as P. aeruginosa isolated from any clinical sample, and "wild-type" as those susceptible to all antibiotics tested. The residential addresses of community-acquired wild-type cases were mapped. Whole-genome sequencing and multilocus sequence typing were used to determine clonality and identify virulence genes. A clinical study in a subset of patients with bloodstream infection compared demographic and clinical characteristics between sequence types (STs). The outbreak lasted 10 months from December 2016 to September 2017 with 3,321 documented cases. At the peak, cases reached 2.3-fold baseline rates. Cases were distributed widely across the city. Multilocus ST 303 was predominant during the outbreak. A total of 51 virulence genes were differentially present in ST303 compared with other STs, including genes involved in biofilm formation, iron uptake, and gut penetration. The investigation confirmed a citywide outbreak of P. aeruginosa. We identified a predominant outbreak-associated clone, ST303, which harbored genes that could contribute to virulence and survival in adverse environmental conditions such as those associated with drought.
• Novel techniques are encouraged to identify nontuberculosis mycobacteria (NTM). • An algorithm incorporating direct molecular identification of NTM is suggested. • Rapid NTM identification can assist in decision-making and prompt treatment initiation.
Botulism, a rare life-threatening toxemia, is probably underdiagnosed in all of its forms in Africa. This study reports the first laboratory-supported case of infant botulism on the African continent. A 10-week-old, previously well infant presented with progressive global weakness, feeding difficulty, and aspiration pneumonia. During a lengthy hospitalization, a rare bivalent Clostridium botulinum strain, producing subtype B3 and F8 toxins and with a new multilocus sequence type, was isolated from stool. The infant was successfully treated with a heptavalent botulinum antitoxin infusion and pyridostigmine. Despite the relative rarity of infant botulism, this case illustrates the importance of maintaining a high level of clinical suspicion when assessing hypotonic infants. The value of modern diagnostic modalities in identifying and characterizing this under-recognized condition is also demonstrated.
Nontuberculous mycobacteria (NTM) infections present a global health challenge. This study describes unidentified mycobacteria species from extrapulmonary sites, using advanced identification and sequencing techniques. Extrapulmonary mycobacteria growth indicator tube primary cultures collected retrospectively between 2019 and 2023, featuring unidentified mycobacteria species detected by GenoType Mycobacterium line probe assays, underwent multilocus targeted next-generation sequencing using Oxford Nanopore Technology, polymerase chain reaction amplicon Sanger sequencing, and Deeplex Myc-TB analysis. Previously collected clinical and laboratory data were reported. A total of 28 cultures, collected from extrapulmonary sites, each from different patients, were included. Mycobacterial mixtures were identified in 19 of 28 (68%) cultures, with four of 28 (14%) showing unidentified species based on sequencing of rpoB and hsp65 targets. Mycobacterium monacense was present in 13 of 28 (46%) of the cultures. Culturable Mycobacterium tuberculosis complex (MTBC) was identified in five extrapulmonary specimens that previously tested negative for MTBC using Xpert MTB/RIF Ultra. The comparative analysis between Sanger and targeted next-generation sequencing using Oxford Nanopore Technology sequencing (for hsp65) demonstrated 27 of 28 (96%) agreement on the predominant strain. Deeplex Myc-TB could not identify NTM-MTBC co-infections in minor subpopulations. This study highlights the role of advanced sequencing in identifying NTM mixtures and mycobacterial co-infections. It calls for ongoing efforts to integrate next-generation sequencing into mycobacteria testing algorithms.