Corrigendum: Global trends of antimicrobial resistance rates in Neisseria gonorrhoeae: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fphar.2024.1284665.].

Global trends of antimicrobial resistance rates in Neisseria gonorrhoeae: a systematic review and meta-analysis.

Background: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae (NG) is a significant public health concern. Objective: The objective of our study was to assess global AMR rates and test them both temporally and geographically. Methods: We conducted a systematic search of relevant reports from international databases up to 2021. The R statistical package was used for all statistical analyses. Results: A total of 225 articles were analyzed, and 432,880 NG isolates were examined. The weighted pooled resistance (WPR) rate of different antibiotics was as follows: ciprofloxacin, 51.6%; tetracycline, 45.4%; trimethoprim/sulfamethoxazole, 42.4%; chloramphenicol, 4.1%; kanamycin, 2.1%; gentamicin, 0.6%; and spectinomycin, 0.3%. The resistance to spectinomycin, gentamicin, and kanamycin decreased over time. Significant differences in antibiotic resistance rates were found between the countries. Conclusion: Our findings reveal a continuous increase in resistance to some antibiotics (tetracycline and ciprofloxacin) historically used for gonorrhea, even after discontinuation. However, encouraging trends of decreasing resistance to spectinomycin, gentamicin, and kanamycin were observed. Continued global monitoring of AMR profiles in NG isolates is essential for informing appropriate treatment strategies and mitigating the threat of untreatable gonorrhea.

Molecular Characterization of Antimicrobial Resistance and Virulence Genotyping among Helicobacter pylori-Positive Dyspeptic Patients in North Iran.

BACKGROUND: Iran has a relatively high prevalence of H. pylori, which correlates with high-risk areas for gastric cancer worldwide. METHODS: Our study aimed to investigate the underlying genetic mechanisms associated with resistance to metronidazole (frxA, rdxA), clarithromycin (23S rRNA), tetracycline (16S rRNA), and fluoroquinolone (gyrA) in H. pylori-positive dyspeptic patients using PCR and sequencing. We further examined the potential correlation between resistance profiles and various virulence genotypes. RESULTS: The rates of genetic mutations associated with resistance to metronidazole, fluoroquinolone, clarithromycin, and tetracycline were found to be 68%, 32.1%, 28.4%, and 11.1%, respectively. Well-documented multiple antibiotic resistance mutations were detected, such as rdxA and frxA (with missense and frameshift alterations), gyrA (Asp91, Asn87), 23S rRNA (A2142G, A2143G), and 16S rRNA (triple-base-pair substitutions AGA926-928→TTC). The cagA+ and vacA s1/m1 types were the predominant genotypes in our study. With the exception of metronidazole and tetracycline, no significant correlation was observed between the cagA+ and cagL+ genotypes and resistance-associated mutations. CONCLUSION: The prevalence of antibiotic resistance-associated mutations in H. pylori was remarkably high in this region, particularly to metronidazole, ciprofloxacin, and clarithromycin. By conducting a simultaneous screening of virulence and resistance genotypes, clinicians can make informed decisions regarding the appropriate therapeutic regimen to prevent the escalation of antibiotic resistance against H. pylori infection in this specific geographical location.

Antibody-Antibiotic Conjugates: A Comprehensive Review on Their Therapeutic Potentials Against BacterialInfections.

INTRODUCTION: Antibodies are significant agents in the immune system and have proven to be effective in treating bacterial infections. With the advancement of antibody engineering in recent decades, antibody therapy has evolved widely. AIM: This review aimed to investigate a new method as a therapeutic platform for the treatment of bacterial infections and explore the novel features of this method in conferring pathogen specificity to broad-spectrum antibiotics. MATERIAL AND METHODS: A literature review was conducted addressing the following topics about antibody-antibiotic conjugates (AACs): (1) structure and mechanism of action; (2) clinical effectiveness; (3) advantages and disadvantages. RESULT: Antibody conjugates are designed to build upon the progress made in the development of monoclonal antibodies for the treatment of diseases. Despite the growing emergence of antibiotic resistance among pathogenic bacteria worldwide, novel antimicrobials have not been sufficiently expanded to combat the global crisis of antibiotic resistance. A recently developed strategy for the treatment of infectious diseases is the use of AACs, which are specifically activated only in host cells. CONCLUSION: A novel therapeutic AAC employs an antibody to deliver the antibiotic to the bacteria. The AACs can release potent antibacterial components that unconjugated forms may not exhibit with an appropriate therapeutic index. This review highlights how this science has guided the design principles of an impressive AAC and discusses how the AAC model promises to enhance the antibiotic effect against bacterial infections.

Investigating the Effectiveness of mqsR-Peptide Nucleic Acid as a Novel Solution for the Eradication of Persister Cells in Clinical Isolates of Escherichia coli.

BACKGROUND: Bacterial persisters are non- or slow-growing phenotypic variants that may be responsible for recalcitrance and relapse of persistent infections and antibiotic failure. In Escherichia coli, mqsRA is a well-known type II toxin-antitoxin system associated with persister cell formation. This study aimed to investigate the efficiency of an antisense peptide nucleic acid (PNA) targeting mqsRA in eliminating E. coli persisters. METHODS: The study included 600 non-duplicated urine samples from adult patients with suspected urinary tract infections. The isolates were subjected to antimicrobial susceptibility testing and bacterial persister cells assay. The presence of mqsRA in the isolates was evaluated by polymerase chain reaction. Finally, expression of the mqsR and mqsA genes was assessed after exposure to normal conditions, stress, and different concentrations of mqsR-PNA (1 - 35 µM). RESULTS: The mqsR gene was significantly overexpressed under stress conditions, which was compensated by the PNA treatment. Complete inhibition of E. coli persister cells was achieved after overnight treatment with the anti-mqsR-PNA at concentrations ≥ 15 µM. CONCLUSIONS: The growth of E. coli persister cells can be inhibited by the anti-mqsR-PNA. Further studies are required to evaluate the effectiveness of this antisense PNA in both preclinical and clinical settings.

Trends of fluoroquinolones resistance in Mycoplasma and Ureaplasma urogenital isolates: Systematic review and meta-analysis.

BACKGROUND: Mycoplasma and Ureaplasma spp. especially M. hominis, U. parvum, and U. urealyticum recognized as an important cause of urogenital infections. Sake of the presence of antibiotic resistance and a continuous rise in resistance, the treatment options are limited, and treatment has become more challenging and costlier. OBJECTIVES: Therefore, this meta-analysis aimed to estimate worldwide resistance rates of genital Mycoplasmas and Ureaplasma to fluoroquinolones (ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin) agents. METHODS: We searched the relevant published studies in PubMed, Scopus, and Embase from until 3, March 2022. All statistical analyses were carried out using the statistical package R. RESULTS: The 30 studies included in the analysis were performed in 16 countries. In the metadata, the proportions of ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin resistance in Mycoplasma and Ureaplasma urogenital isolates were reported 59.8% (95% CI 49.6, 69.1), 31.2% (95% CI 23, 40), 7.3% (95% CI 1, 31), and 5.3% (95% CI 1, 2), respectively. According to the meta-regression, the ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin rate increased over time. There was a statistically significant difference in the fluoroquinolones resistance rates between different continents/countries (P < 0.05). CONCLUSIONS: Based on the results obtained in this systematic review and meta-analysis we recommend the use of the newer group of fluoroquinolones especially levofloxacin as the first choice for the treatment of genital mycoplasmosis, as well as ofloxacin for the treatment of genital infections caused by U. parvum.

Tetracyclines resistance in Mycoplasma and Ureaplasma urogenital isolates derived from human: a systematic review and meta-analysis.

BACKGROUND: Urogenital Mycoplasma infections are considered an important public health problem, owing to the presence of antibiotic resistance or decreased susceptibility, the treatment options are limited. OBJECTIVE: Therefore, this meta-analysis aimed to estimate resistance rates of genital Mycoplasmas to tetracyclines (tetracycline, doxycycline, and minocycline). METHODS: We searched the relevant published studies in PubMed, Scopus, and Embase until 3, March 2022. All statistical analyses were carried out using the statistical package R. RESULTS: The 26 studies included in the analysis were performed in 15 countries. In the metadata, the proportions of tetracycline, doxycycline, and minocycline resistance in Mycoplasma and Ureaplasma urogenital isolates were reported 14.2% (95% CI 8.2-23.2%), 5% (95% CI 3-8.1%), and 11.9% (95% CI 6.3-21.5%), respectively. According to the meta-regression, the tetracycline and minocycline resistance rate decreased over time. Although, the doxycycline resistance rate increased over time. There was a statistically significant difference in the tetracyclines resistance rates between different continents/countries (P < 0.05). CONCLUSION: The prevalence rate and antibiotic susceptibility profiles vary geographically. Therefore, rigorous or improved antimicrobial stewardship, contact tracing, and enhanced intensive surveillance systems are necessitated for preventing the emergence and further spreading of tetracyclines resistance in genital Mycoplasmas.

Bacterial Persister Cells: Mechanisms of Formation, Control, and Eradication.

Bacterial Persister Cells (BPCs) are quiescent, slow-growing or growth-arrested phenotypic variants of normal bacterial cells that are transiently tolerant to antibiotics. It seems that persister cells are the main cause of the recurrence of various chronic infections. Stress response (RpoS-mediated), Toxin-Antitoxin (TA) systems, inhibition of ATP production, Reactive Oxygen Species (ROS), efflux pumps, bacterial SOS response, cell-to-cell communication and stringent response (ppGpp- mediated) are the primary potential mechanisms for persistence cell formation. However, eradicating persistent cells is challenging as the specific molecular mechanisms that initiate their formation remain fuzzy and unknown. Here we reviewed and summarized the current understanding of how bacterial persister cells are formed, controlled, and destroyed.

Global status of phenotypic pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates: an updated systematic review and meta-analysis.

Pyrazinamide (PZA) is an essential first-line tuberculosis drug for its unique mechanism of action active against multidrug-resistant-TB (MDR-TB). Thus, the aim of updated meta-analysis was to estimate the PZA weighted pooled resistance (WPR) rate in M. tuberculosis isolates based on publication date and WHO regions. We systematically searched the related reports in PubMed, Scopus, and Embase (from January 2015 to July 2022). Statistical analyses were performed using STATA software. The 115 final reports in the analysis investigated phenotypic PZA resistance data. The WPR of PZA was 57% (95% CI 48-65%) in MDR-TB cases. According to the WHO regions, the higher WPRs of PZA were reported in the Western Pacific (32%; 95% CI 18-46%), South East Asian region (37%; 95% CI 31-43%), and the Eastern Mediterranean (78%; 95% CI 54-95%) among any-TB patients, high risk of MDR-TB patients, and MDR-TB patients, respectively. A negligible increase in the rate of PZA resistance were showed in MDR-TB cases (55% to 58%). The rate of PZA resistance has been rising in recent years among MDR-TB cases, underlines the essential for both standard and novel drug regimens development.