The growing threat of antibiotic resistance is a significant global health challenge that has intensified in recent years. The burden of antibiotic resistance on public health is augmented due to its multifaceted nature, as well as the slow-paced and limited development of new antibiotics. The threat posed by resistance is now existential in phage therapy, which had long been touted as a promising replacement for antibiotics. Consequently, it is imperative to explore the potential of combination therapies involving antibiotics and phages as a feasible alternative for treating infections with multidrug-resistant bacteria. Although either bacteriophage or antibiotics can potentially treat bacterial infections, they are each fraught with resistance. Combination therapies, however, yielded positive outcomes in most cases; nonetheless, a few combinations did not show any benefit. Combination therapies comprising the synergistic activity of phages and antibiotics and combinations of phages with other treatments such as probiotics hold promise in the treatment of drug-resistant bacterial infections.

Background: Antimicrobial resistance (AMR) poses a global health threat, with lower-middle-income countries bearing a disproportionate burden. Surveillance of AMR under a One Health framework is needed to elucidate the associations among clinical, animal, and environmental AMR. This review aimed to describe the state of AMR in Ghana, focusing on One Health. Method: This review utilized the PRISMA guidelines and major databases to systematically search and analyze AMR in Ghana published from 1 January 2014 to 1 May 2023. Results: Out of the 48 articles that met the inclusion criteria, 28 studies were conducted on humans, 14 studies involved animals, and 6 studies focused on the environment. A total of 48 different pathogens were identified across the human, animal, and environmental sectors, with the most common being Escherichia coli (67%, n = 32), Klebsiella spp. (52%, n = 25), Pseudomonas spp. (40%, n = 19), and Salmonella spp. (38%, n = 18). Generally, a high prevalence of antibiotic resistance was observed among various bacterial species across the sectors. These bacteria exhibited resistance to commonly used antibiotics, with resistance to ampicillin and tetracycline exceeding 80%, and multidrug resistance (MDR) ranging from 17.6% in Shigella spp. to 100% in Acinetobacter spp. Conclusion: This review reaffirms the significant challenge of AMR in Ghana, with a high prevalence observed in the human, animal, and environmental sectors. Key pathogens (e.g., Staphylococcus aureus and Escherichia coli) found across the sectors emphasize the urgent need for a One Health approach to tackle AMR in Ghana.

Fungal pathogens cause a wide range of infections in humans, from superficial to disfiguring, allergic syndromes, and life-threatening invasive infections, affecting over a billion individuals globally. With an estimated 1.5 million deaths annually attributable to them, fungal pathogens are a major cause of mortality in humans, especially people with underlying immunosuppression. The continuous increase in the population of individuals at risk of fungal infections in sub-Saharan Africa, such as HIV patients, tuberculosis patients, intensive care patients, patients with haematological malignancies, transplant (haematopoietic stem cell and organ) recipients and the growing global threat of multidrug-resistant fungal strains, raise the need for an appreciation of the region’s perspective on antifungal usage and resistance. In addition, the unavailability of recently introduced novel antifungal drugs in sub-Saharan Africa further calls for regular evaluation of resistance to antifungal agents in these settings. This is critical for ensuring appropriate and optimal use of the limited available arsenal to minimise antifungal resistance. This review, therefore, elaborates on the multifaceted nature of fungal resistance to the available antifungal drugs on the market and further provides insights into the prevalence of fungal infections and the use of antifungal agents in sub-Saharan Africa.

Bacterial infections are a major public health threat, with a substantial global burden of ∼5 million deaths in 2019, of which ∼1.27 million were attributed to antibiotic resistance. The formation of bacterial biofilms has significantly enhanced bacterial resistance to antibiotics. Worse still, it increases overall bacterial pathogenesis, contributing to inflammation and potentially to carcinogenesis in humans. Biofilm is implicated in approximately 65% of all bacterial infections and 78.2% chronic wound infections. Alarmingly, about 100–1000-fold increase in antibiotic concentration is required to eradicate bacteria within biofilms, further compromising the health of already ill-patients. Therefore, it is imperative to explore potential antibiofilm agents, especially ones with novel mechanisms of action, to clinically manage inpatient biofilms. Bacteriophage (phage) use is a promising evolutionary approach but is also challenged with potential resistance. Bacteria have developed several antiphage defense mechanisms, some of which exhibit synergistic antiphage activity. In this review, we provide several lines of evidence supporting the efficacy of phages against antibiotic-resistant clinical biofilm-forming bacteria. Observations reveal that phage enzymes disrupt biofilm structural components (e.g., EPS, pectate, and hyaluronic acid) and pave the way for phage infection of naked bacterial cells. We further provide insights into the recent advancements in phage use against biofilm-associated antibiotic-resistant bacteria in patients. Current knowledge shows that phages are rapidly evolving and counteracting antiphage bacterial mechanisms. Here, future perspectives to enhance phages efficacy against biofilm resistance are provided to establish their clinical antibiofilm application. Enhancing the clinical application of phages against biofilms requires addressing bacterial host biofilm resistance and optimizing strategies accordingly. Beyond phage cocktail and phage genetic engineering, conjugating phages with antimicrobial agents (eg., antimicrobial peptides) offers a compelling strategy to enhance phage antibiofilm efficacy.

Background: Lower respiratory tract infections (LRTIs) pose a significant threat to global health, causing more than 2 million deaths worldwide. This menace is intensified by the alarming increase in drug resistance, which limits the availability of effective antibiotics for bacterial respiratory infections. Consequently, there is an urgent demand for alternative therapeutic options. Phage therapy (PT) has re-emerged as a promising therapeutic approach and as an adjunct to antibiotic treatment. Objective: This systematic review synthesises the application of PT for LRTIs in humans, providing unified and updated data on the evaluation of the safety and efficacy of PT for LRTIs. Design: Systematic review. Data sources and methods: Following the PRISMA guidelines, a comprehensive search strategy was carried out (spanning January 2000 – February 2024) in four databases: PubMed, Scopus, ScienceDirect and Web of Science to retrieve published records of PT for LRTIs in humans only. The reference list of each included study was evaluated for possible inclusion of other relevant articles. Results: Among the 18 records that fulfilled the inclusion criteria, 70 patients were administered PT. Microbiologically, 71.42% ( n = 50/70) of the patients improved; with either the eradication of the pathogen or a decrease in bacterial load, whilst 15.71% ( n = 11/70) did not record any improvement. About 5.71% (n = 4/70) recorded a partial/incomplete improvement, whilst 7.14% ( n = 5/70) of the patients microbiological outcomes were unspecified. Clinically, up to 74.29% ( n = 52/70) of the patients improved, whilst 10.00% ( n = 7/70) of the patients showed no improvement. Another 2.86% ( n = 2/70) recorded partial/incomplete improvement, whilst 12.86% ( n = 9/70) were uncategorized. Phage titres that yielded positive outcomes ranged from 10 ⁵ to 10 ¹² PFU/mL. Studies that achieved a substantial phage titre at the site of infection frequently observed notable improvements. Regarding the safety of PT, 77.78% ( N = 14/18) of the studies did not record any adverse effects after PT was administered, whilst 16.66% ( n = 3/18) of the studies reported adverse effects. Conclusion: Based on recently published data originating mainly from observational studies, PT has shown considerable efficacy and safety in the treatment of LRTIs. However, there is a lack of uniform methodologies and protocols across different PT cases in the management of LRTIs. Consequently, there is a need for additional clinical studies to establish standardised pharmacokinetic elements and an overall protocol for PT. By doing so, we can fully unlock the potential of PT in effectively managing clinical bacterial infections, including LRTIs.

Meningitis is a significant health concern that is associated with high fatality rates, particularly in resource-limited settings such as Ghana, whose northern regions lie within the African Meningitis Belt. Despite the plethora of primary research data on meningitis in Ghana, a systematic review that provides comprehensive information to guide prevention, control, and management efforts is yet to be undertaken. This systematic review, therefore, aimed at bridging this gap by describing the epidemiology of meningitis in Ghana, including its prevalence, aetiology, and antimicrobial resistance. A comprehensive review of electronic databases, including PubMed and Scopus, was conducted between 2nd and 4th December, 2023, following the established PRISMA guidelines. The search encompassed articles published from 1975 to 2023. With no age limitations on study participants, data extraction was performed on peer-reviewed journal articles reporting primary findings. Studies that exclusively reported on meningitis in animal models, in vitro or in vivo were excluded. Studies with a sample size of less than ten were excluded from the analysis. A meta-analysis was carried out to determine the pooled estimate of meningitis prevalence in the country. There were 71,205 suspected meningitis cases analysed during the study period, with 3865 confirmed, and a pooled (overall) prevalence of 18.13%. Specifically, the cases that occurred during non-outbreak and outbreak periods had a pooled prevalence of 16.22% and 23.91%, respectively. The case fatality rates ranged from 20% to 47% between 1998 and 2015 and from 0.82% to 28.6% between 2016 and 2021. The three northern regions – Upper East (30.8%–54.35%), Northern (16.3%–46.4%), and Upper West (17.96%–38.8%) – had relatively high meningitis prevalence, while the Greater Accra and Ashanti Regions had prevalence ranging between 0.8% and 3.29%. Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae were the predominant isolates, accounting for 0.48%–77.7%, 2.5%–69.5%, and 0.90%–3.40% of the cases, respectively. All bacterial isolates from meningitis cases were susceptible to ceftriaxone. The most common Neisseria meningitidis serogroups were W135, A, Y, and X, while Serotype 1 dominated among the Streptococcus pneumoniae serotypes. There is a disparity in the distribution of meningitis in Ghana, with the highest prevalence occurring in the northern parts of the country. There seems to have been a reduction in the case fatality rate over the years, probably due to interventions such as vaccinations. Ceftriaxone continues to be a suitable treatment option for meningitis. There should be continuous surveillance of meningitis aetiological agents — especially serotyping of the common pathogens — to help guide national vaccination policies and programmes.