Search Results (182)

Background: Mycobacterium ulcerans causes Buruli ulcer (BU), a necrotizing skin disease endemic in over 30 countries. Its toxin, mycolactone, drives tissue destruction, and the infection is transmitted via environmental reservoirs or vectors. Disease patterns vary globally, and an improved understanding of their pathogenesis may enhance current antimicrobial and surgical treatments. Methods: A comprehensive literature search from 1901 to 2025 was conducted across major databases to explore antimicrobial and reconstructive surgical strategies for Mycobacterium ulcerans. Search terms included BU, key antibiotics, and surgical interventions. Relevant English-language studies on treatment outcomes were reviewed to summarize evolving management trends and emerging therapeutic approaches. Results and Discussion: This review highlights the importance of early diagnosis and timely antimicrobial therapy in preventing disease progression and limb loss. It reviews WHO-recommended antibiotic regimens and discusses the theoretical risk of drug resistance, although clinical resistance remains rare and unreported in Australia. Surgical interventions in select cases are crucial, with timing being a significant factor in functional outcomes. The review also covers pediatric-specific challenges, including growth preservation and psychosocial support for young patients. Reconstructive options focus on limb salvage and staged reconstructions, with multidisciplinary care essential for optimal outcomes. The paper advocates for RCTs to refine treatment protocols, surgical guidelines, and explore emerging antibiotic therapies such as telacebec. Conclusions: BU remains a global health challenge, requiring early diagnosis, timely antimicrobial therapy, and surgery in selected cases. Future research will refine treatment and reduce long-term impacts. Full article

Multidrug-resistant (MDR) Mycoplasma genitalium (M. genitalium) presents a significant risk of treatment failure in many sexually transmitted infections (STIs) and can result in persistent and recurrent urethritis or cervicitis. This case report describes a recurrent M. genitalium urethritis resistant to sulfamethoxazole-trimethoprim (TMP-SMX), doxycycline, and moxifloxacin. The infection was ultimately cured after both the removal of a nidus of infection and through the use of Lefamulin. Lefamulin is a novel agent approved for use in community-acquired bacterial pneumonia and bacterial skin infections that may be useful in difficult sexually transmitted infections. Background/Objectives: Deciding whether or not to treat M. genitalium can be challenging as it can be a colonizer, or present with a symptomatic pathogen, and even if it is causing symptoms, it can be drug-resistant. Our objective here is to highlight important considerations on whether or not to treat and, if so, what options exist. Conclusions: In a world of increasing drug-resistant STIs, this case highlights the challenges of managing MDR M. genitalium and how foreign bodies can allow reoccurrence. Also highlighted in this case, Lefamulin appears to be a viable alternative line of treatment of MDR M. genitalium that defies other first-line antibiotics. Full article

Trichomonas vaginalis, a prevalent sexually transmitted protozoan parasite, is associated with adverse birth outcomes, increased risk of HIV and other sexually transmitted infections, infertility, and cervical cancer. Despite its widespread impact, trichomoniasis remains underdiagnosed and underreported globally. Trichomonas vaginalis virus (TVV), a double-stranded RNA (dsRNA) virus infecting T. vaginalis, could impact T. vaginalis pathogenicity. We provide an overview of TVV, including its genomic structure, transmission, impact on protein expression, role in 5-nitroimidazole drug susceptibility, and clinical significance. TVV is a ~5 kbp dsRNA virus enclosed within a viral capsid closely associated with the Golgi complex and plasma membrane of infected parasites. Hypothetical mechanisms of TVV transmission have been proposed. TVV affects protein expression in T. vaginalis, including cysteine proteases and surface antigens, thus impacting its virulence and ability to evade the immune system. Additionally, TVV may influence the sensitivity of T. vaginalis to treatment; clinical isolates of T. vaginalis not harboring TVV are more likely to be resistant to metronidazole. Clinically, TVV-positive T. vaginalis infections have been associated with a range in severity of genital signs and symptoms. Further research into interactions between T. vaginalis and TVV is essential in improving diagnosis, treatment, and the development of targeted interventions. Full article

A backyard cat with symptoms of otitis was transferred to a veterinary clinic in Central Greece. A sample was obtained and P. aeruginosa was isolated. The strain exhibited an extensively drug-resistant (XDR) profile, as it was non-susceptible to all tested agents except colistin. DNA extraction and whole-genome sequencing (WGS) were performed using a robotic extractor and Ion Torrent technology, respectively. The genome was assembled and screened for resistance and virulence determinants. The isolate belonged to the high-risk clone ST308 with a total of 67 antibiotic resistance genes (ARGs) and 221 virulence factor-related genes being identified. No plasmids were detected. The metallo-beta-lactamase (MBL) bla_NDM-1 gene and 46 efflux pumps were included in the strain’s resistome. Both ARGs conferring tolerance to disinfecting agents and biofilm-related genes were identified, associated with the ability of this clone to adapt and persist in healthcare facilities. This case highlights the risk of relevant bacterial clones spreading in the community and even being transmitted to companion animals, causing challenging opportunistic infections to susceptible individuals, while others may become carriers, further spreading the clones to their owners, other animals and the environment. Full article

In this study, we investigated the proportion of transmitted drug resistance (TDR) mutations and human immunodeficiency virus (HIV)-1 subtypes among 487 antiretroviral therapy (ART)-naïve individuals in South Korea from 2021 to 2024 to inform more effective treatment strategies. Consistent with previous reports, subtype B was most prevalent among HIV-1 subtypes at 50.7%; however, its proportion decreased annually (p = 0.047). Various subtypes of circulating recombinant forms (CRFs) were analyzed in this study, resulting in high genetic diversity. The subtype distributions of Korean and non-Korean patients differed, with subtype B (53.7%) and CRF01_AE (34.4%) being dominant in the former and latter, respectively. TDR across antiretroviral drug classes was approximately 3.5% in South Korea. Non-nucleoside reverse transcriptase inhibitors elicited the greatest drug resistance, which increased from 2021 to 2023, with a slight decrease in 2024. The integrase strand transfer inhibitor drugs, elvitegravir and raltegravir, most frequently exhibited high resistance scores. We provide a comprehensive overview of the HIV-1 genetic distribution and TDR patterns in South Korea from 2021 to 2024. Within the broader context of HIV-1 epidemiology in Asia and the Pacific, the findings contribute to a comprehensive understanding of the global distribution of HIV-1 resistance and genotypes, enabling the development of effective interventions. Full article

Trichomonas vaginalis causes one of the most prevalent sexually transmitted infections (STIs). Despite extensive biomolecular research on this protozoan, no efficient molecular tool currently exists for the intraspecific classification of T. vaginalis isolates. In recent years, an incipient tendency has been observed to classify this parasite into two genotypes that correlate in a high percentage with phenotypic characteristics (such as metronidazole resistance and viral endobionts). However, this grouping method has not yet been consolidated by the scientific community. In this sense, Mycoplasma hominis has also been identified as an endobiont of T. vaginalis, but no previous studies on its presence and possible correlation with the two T. vaginalis populations detected have been executed. In the present study, several new T. vaginalis isolates of Spanish origin have been characterized using two molecular markers (microsatellites and single-copy genes), the presence of T. vaginalis virus (TVV) and Mycoplasma, and the resistance to reference drugs. On the basis of our molecular results, the isolates were classified into two groups, as proposed by other researchers. In relation to the biological determinations, the two isolates harboring Mycoplasma were sensible to the reference drugs and were included in the same genotypic group. Although the presence of TVV was more notable in one group than in the other, both groups had TTV+ and TVV− isolates. These findings indicate that genetic grouping does not strongly correlate with susceptibility to reference drugs or endobiont presence, suggesting the need for further research into alternative classification models. Full article

Background: Argentina has reported moderate to high levels of transmitted drug resistance in people living with HIV/AIDS (PLWHA), mostly to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Doravirine (DOR) has a unique resistance profile and retains potent antiviral activity in the presence of the most prevalent NNRTI-associated resistant viruses. Scarce data exist regarding the frequency of DOR resistance-associated mutations (RAMs) in Latin America. We describe the prevalence of DOR RAMs in samples from adults PLWHA in Buenos Aires, Argentina, in the context of a survey of transmitted drug resistance (TDR). Material and Methods: A cross-sectional study was undertaken utilizing samples collected between 2017 and 2021 at two reference HIV clinics. Samples were analyzed for RAMs using the World Health Organization (WHO) mutation list. Mutations to DOR were assessed with the Stanford and Agence Nationale de Recherches sur le SIDA (ANRS) algorithms. Rilpivirine (RPV) RAMs were assessed using the Stanford algorithm. Susceptibility to NNRTIs was evaluated using the HIVdb Program with Stanford and ANRS criteria. Results: Samples from 1667 PLWHA were analyzed: 81.2% were male, with 52.6% identifying as men who have sex with men. According to the WHO list, the overall TDR was 12.1% (n = 203). The prevalence of RAMs was 10.1% (170/1667) for NNRTIs, 4% (67/1667) for nucleoside reverse-transcriptase inhibitors (NRTIs), and 1.7% (30/1667) for protease inhibitors (PIs). The most frequent NNRTI mutations were K103N (5.6%), G190A (0.89%), and K103S (0.77%). The prevalence of DOR RAMs was <2%, with the most common being Y188L (0.53%). Rilpivirine RAM prevalence was 6%. Susceptibility to DOR, RPV, efavirenz, and nevirapine as given by the Stanford algorithm was 97.4%, 92%, 91.4%, and 90.4%, respectively. The ANRS criteria yielded susceptibility rates of 98.3%, 93.3%, 92.3%, and 90.8%, respectively. Regarding NRTIs, thymidine analog mutations (including T215 revertants) were the most frequent RAMs. Among PIs, the most prevalent RAMs were M46L (0.47%) and V82A (0.35%). Conclusions: Our study shows the persistence of moderate to high levels of resistance to first-generation NNRTIs. Despite this, prevalence was low for DOR. Surveillance of TDR remains critical for recommendations of ART initiation. Full article

Antibiotic resistance is increasing at an alarming rate worldwide, in large part due to their misuse and improper disposal. Antibiotics administered to treat human and animal diseases, including feed supplements for the treatment or prevention of disease in farm animals, have contributed greatly to the emergence of a multitude of antibiotic-resistant pathogens. Shewanella is one of many bacteria that have developed antibiotic resistance, and in some species, multiple-antibiotic resistance (MAR). Shewanella is a rod-shaped, Gram-negative, oxidase-positive, and H₂S-producing bacterium that is naturally found in the marine environment. In humans, Shewanella spp. can cause skin and soft tissue infections, septicemia, cellulitis, osteomyelitis, and ear and wound infections. Some Shewanella have been shown to be resistant to a variety of antibiotics, including beta-lactams, aminoglycoside, quinolones, third- or fourth-generation cephalosporins, and carbapenems, due to the presence of genes such as the bla_OXA-class D beta-lactamase-encoding gene, bla_AmpC-class-C beta-lactamase-encoding gene, and the qnr gene. Bacteria can acquire and transmit these genes through different horizontal gene-transmission mechanisms such as transformation, transduction, and conjugation. The genes for antibiotic resistance are present on Shewanella chromosomes and plasmids. Apart from this, heavy metals such as arsenic, mercury, cadmium, and chromium can also increase antibiotic resistance in Shewanella due to co-selection processes such as co-resistance, cross resistance, and co-regulation mechanisms. Antibiotics and drugs enter Shewanella spp. through pores or gates in their cell wall and may be ejected from the bacteria by efflux pumps, which are the first line of bacterial defense against antibiotics. Multiple-drug resistant Shewanella can be particularly difficult to control. This review focuses on the phenotypic and genomic characteristics of Shewanella that are involved in the increase in antimicrobial resistance in this bacterium. Full article

The increasing resistance of Trichomonas vaginalis to the only approved chemical family of drugs for treatment, the 5-nitroimidazoles, has prompted the exploration of new therapeutic agents against this prevalent non-viral sexually transmitted infection. Natural products have emerged as a significant source of novel treatments for trichomoniasis. The aim of this study was to evaluate the anti-T. vaginalis activity of citral (3,7-dimethyl-2,6-octadienal), the main constituent of the essential oil of Cymbopogon species, commonly known as lemongrass. Our findings indicate that citral exhibits a minimum inhibitory concentration (MIC) of 100 μM, effectively inhibiting the growth of T. vaginalis trophozoites within 12 h of exposure, and a 50% inhibitory concentration (IC₅₀) of approximately 40 μM after 24 h. Furthermore, the evaluation of nitric oxide (NO) levels suggests that citral possesses antioxidant properties. Molecular docking studies reveal a weak interaction with three parasite proteins: thioredoxin reductase (TvTrxR), purine nucleoside phosphorylase (TvPNP), and methionine gamma lyase (TvMGL). The present study highlights the potential of citral as a candidate for the development of no-nitroimidazole drugs, offering new avenues for trichomoniasis treatment and underscoring the importance of further investigation into citral’s mechanism of action. Full article

Parasitic infections remain a significant public health challenge in West Africa, contributing to high morbidity and mortality rates, economic burdens, and healthcare system strain. Malaria, soil-transmitted helminths, schistosomiasis, and other parasitic diseases persist due to environmental, socio-economic, and healthcare barriers. A systematic literature search was conducted using databases such as PubMed, Scopus, Web of Science, and Science Direct. Studies published between 2014 and 2024 were screened using predefined eligibility criteria. Cross-sectional and case–control studies reporting on prevalence, diagnostic techniques, and treatment of parasitic infections in West Africa were included. The Rayyan online platform was used for screening, and data extraction focused on study location, prevalence rates, diagnostic methods, and treatment regimens. This review identified the high prevalence rates of malaria, schistosomiasis, and soil-transmitted helminths across various West African countries. Co-infections were frequently reported, particularly among children and pregnant women. Diagnostic methods ranged from traditional microscopy to advanced molecular techniques, though accessibility remained a challenge in resource-limited settings. Treatment strategies, including artemisinin-based combination therapies for malaria and mass drug administration for helminths, showed varying efficacy due to reinfection risks and emerging drug resistance. Factors influencing transmission included environmental conditions, sanitation practices, socio-economic status, and healthcare access. Parasitic infections in West Africa continue to pose significant health and economic challenges. Integrated control programs, enhanced surveillance systems, improved access to diagnostics and treatment, and targeted public health interventions are essential for reducing disease burden. Further research is needed to evaluate the long-term impact of existing interventions and explore innovative solutions for parasite control and elimination. Full article

Malaria has been and remains a significant challenge in Africa and other endemic settings. Roughly, 95% of global morbidity and mortality due to malaria occurs within African populations and affects millions of individuals, especially those living in sub-Saharan countries, predominantly due to disease complications. Cultural factors such as unawareness of and disinterest in using recommended preventive tools and combating the primary host (i.e., the female Anopheles mosquito) play a significant role. This host transmits the malaria-causing Plasmodium parasite by biting an infected individual and spreading it to humans. The current overview focuses on the molecular markers associated with antimalarial drug resistance in Plasmodium falciparum (P. falciparum) in Rwanda, considered an exemplar of sub-Saharan countries where malaria is prevalent and effective policies on the development of malaria treatment, approved recently by WHO in 2025, have been adopted. The prevalence of mutations in key resistance genes, including pfcrt, pfmdr1, and pfdhfr/pfdhps, are linked to resistance against common antimalarial drugs such as chloroquine and sulfadoxine-pyrimethamine (SP). In addition, the Plasmodium falciparum kelch13 (pfk13) gene is linked to resistance against artemisinin, as its mutations can cause delayed parasite clearance and treatment failure. Despite changes in therapeutic use policies owing to high prevalence of variant alleles, which reduce the drug’s efficacy resistance to SP, the gene persists in Rwanda. Malaria parasites are becoming more resistant to chloroquine, leading to diminished effectiveness and slower recovery or treatment failure. Surveillance data reported from several studies provide crucial insights into the evolving trends of resistance markers and are vital for guiding treatment protocols and informing therapeutic use policy decisions. It is important that we continue to maintain and develop the effectiveness of malaria prevention strategies and treatments, due to the multiple types of resistance found in the population. Full article

Neisseria gonorrhoeae (NG) is a globally significant sexually transmitted infection (STI) with increasing antimicrobial resistance (AMR), posing a serious threat to public health. Between 2016 and 2022, the Israeli National NG Reference Center (INNGRC) comprehensively analyzed NG isolates in Israel to determine AMR patterns and sequence types (STs). Antimicrobial susceptibility testing (AST) was performed on 1205 NG isolates using E-test gradient strips, and NG-MAST analysis was conducted on 279 isolates via Sanger sequencing and whole genome sequencing (WGS). Surveillance revealed high resistance rates to ciprofloxacin (54.4%), azithromycin (41.3%), tetracycline, and benzylpenicillin, while all isolates remained susceptible to ceftriaxone and spectinomycin. Multi-drug resistance (MDR) was observed in 8.6% of isolates, and 3% were classified as extensively drug-resistant (XDR). NG-MAST analysis identified 72 distinct STs, with ST292, ST4269, and ST5441 being the most prevalent. ST19665 and ST11461 predominated in 2022, while ST292, ST5441, and ST16169 were more abundant in 2018. The findings highlight the increasing prevalence of AMR in NG in Israel and underscore the importance of continuous surveillance and molecular characterization by reference laboratories like the INNGRC to inform treatment strategies and public health interventions, ultimately reducing the burden of this critical STI. Full article

HIV subtype A6 with the L74I polymorphism, which increases the risk of cabotegravir/rilpivirine treatment failure, causes more and more infections in Poland. In this multicenter, observational, cross-sectional study (2023–2024), we analyzed viral subtypes and drug-resistance mutations to drugs used for long-acting injectable antiretroviral treatment and pre-exposure prophylaxis. Among 357 people with HIV, 247 (69%) were Polish nationals, and 102 (29%) were from former Soviet Union countries. Of the 357 people included, 159 (45%) had subtype B, and 177 (50%) had subtype A6 infections, with 165 (87%) of the latter characterized by the L74I polymorphism. Subtype A6 was more frequent in women (66% vs. 46% in men, p < 0.05) and among people from former Soviet countries (77% vs. 39% in Polish nationals, p < 0.05). About 40% of people had either drug-resistance mutations for cabotegravir/rilpivirine or HIV A6 subtype with the L74I polymorphism; 4.5% had both of these conditions. Compared to subtype B infections, subtype A6 infections were characterized by more frequent major transmitted drug-resistance mutations for non-nucleoside reverse transcriptase inhibitors (8.5% vs. 1.9%, p = 0.007) and rilpivirine (5.1% vs. 0.6%, p = 0.016). Due to the frequent occurrence of the L74I polymorphism and drug-resistance mutations in HIV A6 subtype infection, about 40% of people with HIV in Poland may be at risk of long-acting injectable treatment failure. Full article

Streptococcus pyogenes is an important zoonotic Gram-positive bacterium that appears in chains, without spores or flagella, and belongs to the beta-hemolytic streptococci. It can be transmitted through droplets or contact, with the preferred antibiotics being penicillin, erythromycin, or cephalosporins. However, the misuse of these drugs has led to antibiotic resistance, posing a significant threat to both human and animal health. Studying resistance genes encoding proteins is crucial for mitigating the emergence of resistant strains and improving treatment outcomes. Interestingly, a dinucleotide known as diadenosine tetraphosphate (Ap4A) exists in Streptococcus pyogenes; its accumulation in response to various stress signals can inhibit bacterial pathogenicity and enhance antibiotic susceptibility. Our research focuses on the Sp-yqeK protein, which we have identified as a hydrolase that symmetrically cleaves Ap4A. The Sp-yqeK protein effectively cleaves Ap4A, producing adenosine diphosphate (ADP) molecules. Results indicate that this enzyme exhibits optimal activity at pH 7.0 and a temperature of 45 °C. Furthermore, we determined the crystal structure of the Sp-yqeK, Mg²⁺, and ADP complex at a resolution of 2.0 Å, providing insights into the interactions crucial for catalytic efficiency between Sp-yqeK and ADP. This complex reveals unique folding characteristics of the HD domain superfamily proteins, accommodating both ADP and Mg²⁺. These components are securely embedded into the polar cavity of the yqeK protein through conserved residues (His²⁹, Lys⁶², His⁹¹, His¹¹⁷, Asp¹³⁵, Leu¹⁷², Phe¹⁸⁰, and Thr¹⁸³), highlighting the residues responsible for Ap4A hydrolysis and Mg²⁺ binding. Our research offers a deeper understanding of the hydrolysis mechanism of Ap4A and the specificity of Sp-yqeK, providing structural insights that may support future studies on antibiotic resistance in Streptococcus pyogenes and other Gram-positive bacteria. Full article

Antimicrobial resistance (AMR) in Campylobacter species, particularly C. jejuni and C. coli, poses a significant public health threat. These bacteria, which are commonly found in livestock, poultry, companion animals, and wildlife, are the leading causes of foodborne illnesses, often transmitted through contaminated poultry. Extensive exposure to antibiotics in human and veterinary medicine creates selection pressure, driving resistance through mechanisms such as point mutations, horizontal gene transfer, and efflux pumps. Resistance to fluoroquinolones, macrolides, and tetracyclines complicates treatment and increases the risk of severe infections. Drug-resistant Campylobacter is transmitted to humans via contaminated food, water, and direct contact with animals, highlighting its zoonotic potential. Addressing this challenge requires effective interventions. Pre-harvest strategies like biosecurity and immune-based methods reduce bacterial loads on farms, while post-harvest measures, including carcass decontamination and freezing, limit contamination. Emerging approaches, such as bacteriocins and natural antimicrobials, offer chemical-free alternatives. Integrated, multidisciplinary interventions across the food chain are essential to mitigate AMR transmission and enhance food safety. Sustainable agricultural practices, antimicrobial stewardship, and innovative solutions are critical to curbing Campylobacter resistance and protecting global public health. Our review examines the dynamics of antimicrobial resistance in Campylobacter and presents current strategies to mitigate Campylobacter-related AMR, offering valuable insights for antimicrobial control in the poultry industry. Full article