Key Antibiotics Research Articles

Prolonged sitafloxacin and doxycycline combination regimen for treating infections by highly resistant Mycoplasma genitalium.

Mycoplasma genitalium, which causes sexually transmitted diseases, is increasingly resistant to key antibiotics such as macrolides and quinolones, posing a challenge for treatment. To assess the effectiveness of prolonged sitafloxacin and doxycycline combination therapy as a new alternative treatment strategy for highly drug-resistant M. genitalium strains. A prospective cohort study was conducted at the National Center for Global Health and Medicine, Tokyo, Japan, from 1 January 2020 to 31 October 2022. Patients with M. genitalium urogenital or rectal infections and those who did not receive the initial sitafloxacin monotherapy were included. Patients were administered sitafloxacin and doxycycline for 21 days as salvage therapy. M. genitalium isolates were tested for parC, gyrA and 23S rRNA resistance-associated mutations. Twenty-seven patients received the combination therapy. All M. genitalium strains available for resistance analysis had parC (24/24) and macrolide resistance-associated (25/25) mutations, and 68% (17/25) had gyrA mutations. The overall cure rate was 77.8%. For strains with concurrent parC and gyrA mutations, the cure rate was 68.8% (P = 0.053) compared with that for monotherapy (37.5%). Prolonged combination therapy is highly effective against M. genitalium strains with concurrent parC and gyrA mutations. Future research should focus on establishing the optimal treatment duration and monitoring the risk of resistance.

The impact of antibiotic induction on virulence and antibiotic resistance in Klebsiella pneumoniae: a comparative study of CSKP and CRKP strains.

Klebsiella pneumoniae is an opportunistic pathogen causing nosocomial infections, classified into carbapenem-sensitive and carbapenem-resistant strains. Understanding the virulence factors and antibiotic resistance of these strains is essential for effective clinical management. This study compared the virulence genes and antibiotic resistance profiles of 50 CSKP and 50 CRKP strains, examining their expression under antibiotic pressure and the mechanisms contributing to their pathogenicity. Virulence genes (rmpA, rmpA2, iucA, iutA, Peg-344, ybts, iroB) were detected in both strains using polymerase chain reaction (PCR). Antibiotic susceptibility testing established minimum inhibitory concentrations (MICs) for key antibiotics. Gene expression analysis was performed with quantitative reverse transcription PCR (qRT-PCR) after 10 days of antibiotic exposure. CSKP strains exhibited significantly higher positivity rates for virulence genes compared to CRKP strains. CRKP strains predominantly expressed resistance genes KPC, SHV, and CTX-M3, whereas no resistance genes were found in CSKP. Antibiotic susceptibility tests showed increased MICs, particularly for ciprofloxacin and imipenem, following antibiotic induction. CSKP demonstrated elevated expression of rmpA and rmpA2, while CRKP showed increased expression of SHV, and KPC after antibiotic exposure. This study highlights the intricate relationship between virulence and resistance in Klebsiella pneumoniae. CSKP strains show strong virulence factor expression, while CRKP strains adapt to antibiotic pressure through altered gene expression patterns. These findings underscore the urgent need for continuous surveillance and innovative therapeutic strategies to combat multidrug-resistant Klebsiella pneumoniae infections.

Whole Genome Sequencing (WGS) Analysis of Antimicrobial Resistance (AMR) Milk and Dairy-Derived Pathogens from Anand, Gujarat, India

This study aimed to evaluate the antimicrobial resistance (AMR) patterns and genomic characteristics of Enterococcus faecalis, Enterococcus faecium, and Staphylococcus aureus strains isolated from dairy products, including buttermilk, curd, ice cream, and sweets, in the Anand region of Gujarat, India. A total of 205 isolates were analyzed, with the highest contamination levels found in buttermilk and curd. The bacterial isolates were identified using biochemical tests and advanced Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) mass spectrometry. Antimicrobial susceptibility testing (AST) was performed using the Kirby-Bauer disk diffusion method, following CLSI guidelines, focusing on common antibiotics used for treating dairy-related bacterial infections. Resistance profiles were analyzed using WHONET software.s The findings revealed significant multidrug resistance (MDR), particularly among E. faecium and E. faecalis, with over 95% resistance to key antibiotics, including linezolid, ciprofloxacin, cefpodoxime, and carbapenems. Many strains were classified as MDR, XDR, and PDR. Staphylococcus aureus also exhibited substantial resistance to penicillin and enrofloxacin. whole-genome sequencing (WGS) and phylogenetic analysis to identify AMR determinants and conduct nucleotide sequence alignment. The study identified several antibiotic resistance genes, including LiaF, which regulates the expression of LiaR and LiaS genes. WGS revealed that genes such as GdpD, MprF, and PgsA encode intrinsic resistance determinants, contributing to antibiotic resistance. Additional AMR mechanisms were identified, including ABC transporter efflux pumps and the regulation of resistance genes by LiaR and LiaS. Phylogenetic analysis indicates a close relationship between Enterococcus faecium 640 1352.18624 and Enterococcus durans FB129-CNAB-4 883162.3.

A Decade of Antimicrobial Resistance in Human and Animal Campylobacter spp. Isolates.

Objectives: Campylobacter spp. remain a leading cause of bacterial gastroenteritis worldwide, with resistance to antibiotics posing significant challenges to treatment and public health. This study examines profiles in antimicrobial resistance (AMR) for Campylobacter isolates from human and animal sources over the past decade. Methods: We conducted a comprehensive review of resistance data from studies spanning ten years, analyzing profiles in resistance to key antibiotics, ciprofloxacin (CIP), tetracycline (TET), erythromycin (ERY), chloramphenicol (CHL), and gentamicin (GEN). Data were collated from various regions to assess global and regional patterns of resistance. Results: The analysis reveals a concerning trend of increasing resistance patterns, particularly to CIP and TET, across multiple regions. While resistance to CHL and GEN remains relatively low, the high prevalence of CIP resistance has significantly compromised treatment options for campylobacteriosis. Discrepancies in resistance patterns were observed between human and animal isolates, with variations across different continents and countries. Notably, resistance to ERY and CHL showed regional variability, reflecting potential differences in antimicrobial usage and management practices. Conclusions: The findings underscore the ongoing challenge of AMR in Campylobacter, highlighting the need for continued surveillance and research. The rising resistance prevalence, coupled with discrepancies in resistance patterns between human and animal isolates, emphasize the importance of a One Health approach to address AMR. Enhanced monitoring, novel treatment strategies, and global cooperation are crucial for mitigating the impact of resistance and ensuring the effective management of Campylobacter-related infections.

Exploring the Role of the Environment as a Reservoir of Antimicrobial-Resistant Campylobacter: Insights from Wild Birds and Surface Waters.

Antimicrobial resistance (AMR) is a growing global health challenge, compromising bacterial infection treatments and necessitating robust surveillance and mitigation strategies. The overuse of antimicrobials in humans and farm animals has made them hotspots for AMR. However, the spread of AMR genes in wildlife and the environment represents an additional challenge, turning these areas into new AMR hotspots. Among the AMR bacteria considered to be of high concern for public health, Campylobacter has been the leading cause of foodborne infections in the European Union since 2005. This study examines the prevalence of AMR genes and virulence factors in Campylobacter isolates from wild birds and surface waters in Luxembourg. The findings reveal a significant prevalence of resistant Campylobacter strains, with 12% of C. jejuni from wild birds and 37% of C. coli from surface waters carrying resistance genes, mainly against key antibiotics like quinolones and tetracycline. This study underscores the crucial role of the environment in the spread of AMR bacteria and genes, highlighting the urgent need for enhanced surveillance and control measures to curb AMR in wildlife and environmental reservoirs and reduce transmission risks to humans. This research supports One Health approaches to tackling antimicrobial resistance and protecting human, animal, and environmental health.

Evaluation of EUCAST rapid antimicrobial susceptibility test directly from positive blood culture for Pseudomonas aeruginosa.

In this study, we evaluated the performance of the EUCAST RAST method on a collection of 154 clinical strains of P. aeruginosa, including strains resistant to ceftazidime and carbapenems. While the test is convenient for routine laboratories, we observed significant rates of VME (ranging from 0.0 to 15.0%) and ME (ranging from 1.3 to 16.3%) after 6h, particularly for key antibiotics such as ceftazidime, piperacillin/tazobactam, and meropenem. Extending the incubation time to 8h may improve results (CA ranging from 87.2 to 99%), but caution is required in interpretation due to persistence of VME (ranging from 0.0 to 15.6%) and ME (ranging from 0.0 to 11.7%).

Spatiotemporal dynamics, bioaccumulation, and critical influencing factors of antibiotics in tilapia aquaculture: A study on source identification and environmental fate within typical farming systems

This study investigated the spatiotemporal dynamics, bioaccumulation, and critical influencing factors of antibiotics in tilapia aquaculture, focusing on source identification and environmental fate within typical farming systems. The results revealed a progressive increase in antibiotic concentrations in pond water and sediments over the cultivation period, with suspended solids and chemical oxygen demand identified as significant environmental factors influencing the distribution and dissemination of antibiotics. The aquaculture water source was the primary contributor of antibiotics in the farming system. Furthermore, the bioaccumulation factor (BAF) calculations indicated varying degrees of antibiotic enrichment in tilapia tissues, with sulfadimethoxine exhibiting the highest BAFs. Correlation analyses, redundancy analysis, and multivariate linear regression analysis provided insights into the relationship between environmental factors and antibiotics, identifying key antibiotics and influencing factors. The study highlighted the importance of managing and treating water sources to reduce the inflow of antibiotics into aquaculture systems and emphasized the need for non-antibiotic aquaculture practices to minimize the impact on the environment and public health. In conclusion, this research contributes valuable information for the development of effective management strategies and policies aimed at curbing antibiotic pollution in aquaculture environments, ensuring the sustainability of the aquaculture industry, and protecting ecosystem and consumer health.

Salmonella spp. in Domestic Ruminants, Evaluation of Antimicrobial Resistance Based on the One Health Approach-A Systematic Review and Meta-Analysis.

Salmonella spp. pose a global threat as a leading cause of foodborne illnesses, particularly prevalent in the European Union (EU), where it remains the second cause of foodborne outbreaks. The emergence of antimicrobial resistance (AMR) in Salmonella spp. has become a critical concern, complicating treatment strategies and escalating the risk of severe infections. The study focuses on large and small ruminants, identifying a prevalence of Salmonella spp. in slaughterhouses and revealing varied AMR rates across antimicrobial families throughout a meta-analysis. Also, comparison with AMR in human medicine was carried out by a systematic review. The results of the present meta-analysis displayed a prevalence of Salmonella spp. in large and small ruminants at slaughterhouses of 8.01% (8.31%, cattle; 7.04%, goats; 6.12%, sheep). According to the AMR of Salmonella spp., 20, 14, and 13 out of 62 antimicrobials studied were classified as low (<5%), high (>5% but <10%), and very high (>10%), respectively. Salmonella spp. did not display AMR against aztreonam, mezlocillin, ertapenem, meropenem, cefoxitin, ceftazidime, levofloxacin, tilmicosin, linezolid, fosfomycin, furazolidone, quinupristin, trimethoprim and spectinomycin. In contrast, a prevalence of 100% of AMR has been described against ofloxacin, lincomycin, and cloxacillin. In the context of the main antibiotics used in the treatment of human salmonellosis, azithromycin was shown to have the highest resistance among Salmonella spp. isolates from humans. Regarding cephalosporins, which are also used for the treatment of salmonellosis in humans, the prevalence of Salmonella spp. resistance to this class of antibiotics was similar in both human and animal samples. Concerning quinolones, despite a heightened resistance profile in Salmonella spp. isolates from ruminant samples, there appears to be no discernible compromise to the efficacy of salmonellosis treatment in humans since lower prevalences of AMR in Salmonella spp. isolated from human specimens were observed. Although the resistance of Salmonella spp. indicates some degree of concern, most antibiotics are not used in veterinary medicine. Thus, the contribution of cattle, sheep and goats to the rise of antibiotic resistance of Salmonella spp. and its potential impact on public health appears to be relatively insignificant, due to their low prevalence in carcasses and organs. Nevertheless, the observed low prevalence of Salmonella spp. in ruminants at slaughterhouse and the correspondingly low AMR rates of Salmonella spp. to key antibiotics employed in human medicine do not indicate that ruminant livestock poses a substantial public health risk concerning the transmission of AMR. Thus, the results observed in both the meta-analysis and systematic review suggests that AMR is not solely attributed to veterinary antibiotic use but is also influenced by factors such as animal health management (i.e., biosecurity measures, prophylactic schemes) and human medicine.

Phenotypic and Molecular Characterization of Vancomycin and Linezolid Resistance in Clinical Isolates of Staphylococcus aureus

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections and poses a significant global challenge due to its high pathogenicity and rapid spread among patients. Vancomycin and linezolid are key antibiotics for treating staphylococcal MRSA infections. Objectives: This study aimed to investigate resistance to vancomycin and linezolid in clinical isolates of S. aureus. Methods: In this study, 270 S. aureus isolates were collected from patients admitted to hospitals in Tehran and Qazvin. Strain identification was performed using biochemical methods and femA gene amplification. Resistance to methicillin and vancomycin was determined using disk diffusion, minimum inhibitory concentration (MIC) determination, and E-test methods. Methicillin resistance was also assessed by detecting the presence of the mecA and mecC genes. Resistance to vancomycin and linezolid was evaluated by examining the presence of vanA, B, C, and cfr genes using PCR and sequencing. Results: Out of 270 S. aureus isolates, 152 (56.3%) were identified as MRSA, with 144 (94.7%) of these MRSA isolates containing the mecA gene. Two (0.7%) VRSA isolates were observed, and the vanA gene was detected in both. Additionally, four VISA (1.4%) isolates were identified, but the vanA gene was not detected in any of the VISA strains. None of the isolates contained the mecC, vanB, or vanC genes. Among the 10 (3.7%) linezolid-resistant isolates, none contained the cfr gene. Conclusions: The results of this study demonstrated a high prevalence of MRSA isolates, which can lead to treatment failure with beta-lactam antibiotics. The emergence and spread of VRSA and VISA isolates pose a serious concern for the healthcare system, particularly in the treatment of MRSA infections. Therefore, the findings emphasize the need for appropriate monitoring and control measures to prevent the emergence and transmission of MRSA and VRSA strains. Vancomycin and linezolid remain suitable drugs for treating these infections.

Structural analysis of neomycin B and kanamycin A binding Aminoglycosides Modifying Enzymes (AME) and bacterial ribosomal RNA.

Aminoglycosides are crucial antibiotics facing challenges from bacterial resistance. This study addresses the importance of aminoglycoside modifying enzymes in the context of escalating resistance. Drawing upon over two decades of structural data in the Protein Data Bank, we focused on two key antibiotics, neomycin B and kanamycin A, to explore how the aminoglycoside structure is exploited by this family of enzymes. A systematic comparison across diverse enzymes and the RNA A-site target identified common characteristics in the recognition mode, while assessing the adaptability of neomycin B and kanamycin A in various environments.

Pediatric Urinary Tract Infections at a Tertiary Care Center: Microbial Diversity and Antibiotic Resistance Patterns

Abstract Introduction: Urinary tract infection (UTI) remains a prevalent bacterial infection among the pediatric age group, ranking as the third-most common bacterial infection in children in developing countries, following gastrointestinal and respiratory tract infections. It continues to pose a significant health challenge. Materials and Methods: The urine samples underwent gross examination, wet mount, and Gram stain. Semiquantitative cultures were conducted on conventional media (MacConkey agar, blood agar, and CLED agar) and UTI chromogenic media. Uropathogen identification employed standard microbiological techniques. Antibiotic susceptibility was determined using the Kirby–Bauer disk diffusion method, with interpretation based on CLSI guidelines. Plates were incubated overnight, and clear zone diameters around antibiotic discs were measured for sensitivity or resistance determination. Results: The study comprised 64.75% male children and 35.25% female children. Analyzing the age distribution, the majority of participants fell within the age range of 1–5 years (35%), followed by those &lt;1 year (33.75%), and the age group of 5–12 years, accounting for 31.25% of the total 400 participants. The findings from our investigation revealed a UTI prevalence of 17.25%, with Escherichia coli and Klebsiella emerging as the predominant uropathogens. Notably, these pathogens exhibited a significant susceptibility to carbapenems, nitrofurantoin, and amikacin. Conclusion: Our study identified a male predominance and various age distributions among UTI patients. Antibiotic susceptibility patterns revealed E. coli and Klebsiella pneumoniae’s high sensitivity to key antibiotics, whereas Enterococcus spp. exhibited significant high-level aminoglycoside resistance. This study underscores the importance of tailored antibiotic strategies based on local resistance profiles to combat UTIs effectively.

The microbiological quality, shelf-life, and multidrug-resistant Salmonella contamination rates assessment in chicken giblets purchased from live poultry shops

The objective of the current study was to assess the shelf-life durations and hygienic standards of chicken giblets purchased from Egyptian live poultry outlets compared to the Egyptian Standardization Organization criteria. Salmonella prevalence and antibiotic-resistance profiles were also described. On the first day, forty-five giblet samples were randomly collected and evaluated for aerobic plate count (APC), coliform, Escherichia coli, Staphylococcus and Staphylococcus aureus, and multidrug-resistant Salmonella contamination rates using culturing methods, matrix-assisted laser desorption ionization-time of flight mass spectrometry, and the VITEK® −2 system. Four- and five-day shelf-life durations were assessed. All chicken giblets had acceptable APC levels below the 6 log cfu/g on the collection day, but 27 % were contaminated with Salmonella Enteritidis, rendering them unfit. More than 2-log CFU/gm of Escherichia coli and Staphylococcus aureus contamination was identified in 64 % and 58 % of the giblets, respectively. All targeted indices surpassed maximum authorized requirements after four and five days of chilling at 4 °C, coupled with the detection of obvious greenish discoloration and off odor. All twelve Salmonella Enteritidis were vulnerable to carbapenems, cefepime, and piperacillin/tazobactam, but 83 % were multidrug-resistant (MDR), with four demonstrating extended-spectrum beta-lactam resistance. This could be the first Egyptian report identifying such a high prevalence rate of Salmonella and MDR to key antibiotics in chicken giblets. The current study encourages Egyptian authorities to reevaluate laws governing live poultry outlets to reduce the risk of disease exposure, including the National Egyptian Food Safety Authority's direct supervision over these outlets to establish a stringent safety program.

Generalizability of machine learning in predicting antimicrobial resistance in E. coli: a multi-country case study in Africa.

Antimicrobial resistance (AMR) remains a significant global health threat particularly impacting low- and middle-income countries (LMICs). These regions often grapple with limited healthcare resources and access to advanced diagnostic tools. Consequently, there is a pressing need for innovative approaches that can enhance AMR surveillance and management. Machine learning (ML) though underutilized in these settings, presents a promising avenue. This study leverages ML models trained on whole-genome sequencing data from England, where such data is more readily available, to predict AMR in E. coli, targeting key antibiotics such as ciprofloxacin, ampicillin, and cefotaxime. A crucial part of our work involved the validation of these models using an independent dataset from Africa, specifically from Uganda, Nigeria, and Tanzania, to ascertain their applicability and effectiveness in LMICs. Model performance varied across antibiotics. The Support Vector Machine excelled in predicting ciprofloxacin resistance (87% accuracy, F1 Score: 0.57), Light Gradient Boosting Machine for cefotaxime (92% accuracy, F1 Score: 0.42), and Gradient Boosting for ampicillin (58% accuracy, F1 Score: 0.66). In validation with data from Africa, Logistic Regression showed high accuracy for ampicillin (94%, F1 Score: 0.97), while Random Forest and Light Gradient Boosting Machine were effective for ciprofloxacin (50% accuracy, F1 Score: 0.56) and cefotaxime (45% accuracy, F1 Score:0.54), respectively. Key mutations associated with AMR were identified for these antibiotics. As the threat of AMR continues to rise, the successful application of these models, particularly on genomic datasets from LMICs, signals a promising avenue for improving AMR prediction to support large AMR surveillance programs. This work thus not only expands our current understanding of the genetic underpinnings of AMR but also provides a robust methodological framework that can guide future research and applications in the fight against AMR.

Challenges for global antibiotic regimen planning and establishing antimicrobial resistance targets: implications for the WHO Essential Medicines List and AWaRe antibiotic book dosing.

SUMMARYThe World Health Organisation's 2022 AWaRe Book provides guidance for the use of 39 antibiotics to treat 35 infections in primary healthcare and hospital facilities. We review the evidence underpinning suggested dosing regimens. Few (n = 18) population pharmacokinetic studies exist for key oral AWaRe antibiotics, largely conducted in homogenous and unrepresentative populations hindering robust estimates of drug exposures. Databases of minimum inhibitory concentration distributions are limited, especially for community pathogen-antibiotic combinations. Minimum inhibitory concentration data sources are not routinely reported and lack regional diversity and community representation. Of studies defining a pharmacodynamic target for ß-lactams (n = 80), 42 (52.5%) differed from traditionally accepted 30%-50% time above minimum inhibitory concentration targets. Heterogeneity in model systems and pharmacodynamic endpoints is common, and models generally use intravenous ß-lactams. One-size-fits-all pharmacodynamic targets are used for regimen planning despite complexity in drug-pathogen-disease combinations. We present solutions to enable the development of global evidence-based antibiotic dosing guidance that provides adequate treatment in the context of the increasing prevalence of antimicrobial resistance and, moreover, minimizes the emergence of resistance.

Estimation of country-specific tuberculosis resistance antibiograms using pathogen genomics and machine learning

BackgroundGlobal tuberculosis (TB) drug resistance (DR) surveillance focuses on rifampicin. We examined the potential of public and surveillance Mycobacterium tuberculosis (Mtb) whole-genome sequencing (WGS) data, to generate expanded country-level resistance...

Empiric therapy for community acquired urinary tract infection in an era of increasing antimicrobial resistance

Community-acquired urinary tract infections (CA-UTIs) are widespread bacterial infections often necessitating empirical antibiotic therapy. However, the escalating antimicrobial resistance (AMR) poses a grave threat to treatment efficacy. This study aims to assess the prevalence of AMR in uropathogens causing CA-UTIs and its implications for empirical therapy. The study analyzed data from a tertiary care hospital, to determine AMR rates in common uropathogens, including and . Resistance levels to key antibiotics, such as Ampicillin, Ciprofloxacin, and Norfloxacin, were evaluated. Significant resistance rates were observed in uropathogens, with and showing marked resistance. Notably, resistance to commonly prescribed antibiotics like Ampicillin, Ciprofloxacin, and Norfloxacin was widespread, highlighting the severity of the AMR crisis. The increasing AMR in CA-UTIs calls for a comprehensive approach. Strategies including local resistance pattern monitoring, antimicrobial stewardship programs and the recommendation of drugs like nitrofurantoin (with lower drug resistance potential) are crucial to maintain the effectiveness of empirical therapy. This study underscores the urgent need for collaborative efforts to address AMR, ensuring effective CA-UTI management and safeguarding public health.

Wastewater surveillance for antibiotics and resistance genes in a river catchment: Spatiotemporal variations and the main drivers

Wastewater-based epidemiology (WBE) is used for mining information about public health such as antibiotics resistance. This study investigated the distribution profiles of six types of antibiotic resistance genes (ARGs) in wastewater and rivers in Wuhu City, China. The levels of ARGs found in the Qingyijiang River were significantly higher than other rivers, and were comparable to effluent levels. Among the ARGs, sulfonamides ARGs and intI1 were the predominant in both wastewaters and rivers. Additionally, the concentrations of ARGs were higher on weekends as opposed to weekdays. Their distribution patterns remained consistent inter-week and inter-season using linear regression analysis (p < 0.001). Interestingly, the occurrence levels of ARGs in wastewaters during spring were significantly higher than in autumn, although insignificant in rivers. The apparent removal rate of ARGs in domestic wastewater sources ranged from 61.52–99.29%, except for qepA (-1.91% to 81.09%), whereas the removal rates in mixed domestic and industrial wastewaters showed a marked decrease (-92.94% to 76.67%). A correlation network analysis revealed that azithromycin and erythromycin were key antibiotics, while blaNDM-1, tetM, tetB, and ermB were identified as key ARGs. Sulfonamide and fluoroquinolone antibiotics, and tetracycline and macrolide ARGs were the primary contributors. Linear mixed models demonstrated that socio-economic variables positively impacted the occurrence levels of ARGs, whereas wastewater flow and river runoff were the negative drivers for their concentrations in wastewaters and surface waters, respectively. Overall, this WBE study contributes to the understanding of spatiotemporal profiles and main drivers of the occurrence of ARGs in wastewater and receiving water.

Primary antibiotic resistance of Helicobacter pylori in the Asia-Pacific region between 1990 and 2022: an updated systematic review and meta-analysis

We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic resistance continues to rise is unknown. Therefore, we aimed to assess the latest prevalence of H pylori antibiotic resistance in this region. We did an updated systematic review and meta-analysis of observational studies and randomised controlled trials published in PubMed, Embase, and Cochrane Library between Jan 1, 1990, and July 12, 2023. Studies investigating primary H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline in individuals naive to eradication therapy in the Asia-Pacific region (as defined by the UN geoscheme) were eligible for inclusion. There were no language restrictions. Studies that focused on specific subpopulations (eg, children) were excluded. Using a standardised extraction form, two authors independently reviewed and extracted summary data from all eligible articles. The updated prevalence of antibiotic resistance was generated by meta-analysis under a random-effects model and subgroup analyses were done by countries and periods of study. Between-study variability was assessed by use of I2. The study is registered in PROSPERO, CRD42022339956. A total of 351 studies, including 175 new studies and 176 studies from our previous analysis, were included in this meta-analysis. The overall prevalence of primary antibiotic resistance of H pylori between 1990 and 2022 was 22% (95% CI 20-23; I2=96%) for clarithromycin, 52% (49-55; I2=99%) for metronidazole, 26% (24-29; I2=96%) for levofloxacin, 4% (3-5; I2=95%) for tetracycline, and 4% (3-5; I2=95%) for amoxicillin. Prevalence varied considerably between countries and across study periods. From 1990 to 2022, the prevalence of primary resistance increased for clarithromycin, metronidazole, and levofloxacin but remained stable for amoxicillin and tetracycline. The latest primary resistance prevalences were 30% (95% CI 28-33; I2=93%) for clarithromycin, 61% (55-66; I2=99%) for metronidazole, 35% (31-39; I2=95%) for levofloxacin, 4% (2-6; I2=96%) for tetracycline, and 6% (4-8; I2=96%) for amoxicillin in the Asia-Pacific region. Treatment guidelines should be adapted in response to the rising primary resistance of key antibiotics for H pylori eradication. A global policy to control and monitor the antibiotic resistance of H pylori is urgently needed. Ministry of Health and Welfare of Taiwan, National Science and Technology Council of Taiwan, and National Taiwan University. For the Chinese translation of the abstract see Supplementary Materials section.

Systematic review of room temperature stability of key beta-lactam antibiotics for extended infusions in inpatient settings

BackgroundExtended infusion (EI) of beta-lactam antibiotics may offer clinical benefits aligned with improved probability of target attainment for critical pharmacokinetic/pharmacodynamic parameters that correlate with efficacy. There is much research interest...

Functional Whole Genome Screen of Nutrient-Starved Mycobacterium tuberculosis Identifies Genes Involved in Rifampin Tolerance.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), poses a global health challenge and is responsible for over a million deaths each year. Current treatment is lengthy and complex, and new, abbreviated regimens are urgently needed. Mtb adapts to nutrient starvation, a condition experienced during host infection, by shifting its metabolism and becoming tolerant to the killing activity of bactericidal antibiotics. An improved understanding of the mechanisms mediating antibiotic tolerance in Mtb can serve as the basis for developing more effective therapies. We performed a forward genetic screen to identify candidate Mtb genes involved in tolerance to the two key first-line antibiotics, rifampin and isoniazid, under nutrient-rich and nutrient-starved conditions. In nutrient-rich conditions, we found 220 mutants with differential antibiotic susceptibility (218 in the rifampin screen and 2 in the isoniazid screen). Following Mtb adaptation to nutrient starvation, 82 mutants showed differential antibiotic susceptibility (80 in the rifampin screen and 2 in the isoniazid screen). Using targeted mutagenesis, we validated the rifampin-hypersusceptible phenotype under nutrient starvation in Mtb mutants lacking the following genes: ercc3, moeA1, rv0049, and rv2179c. These findings shed light on potential therapeutic targets, which could help shorten the duration and complexity of antitubercular regimens.