Can the use of azithromycin during labour reduce the incidence of infection among puerperae and newborns? A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection among mothers and newborns. DATA SOURCES: We independently searched the PubMed, Web of Science, Cochrane Library and EMBASE databases for relevant studies published before February, 2024. METHODS: We included RCTs that evaluated the effect of prenatal oral or intravenous azithromycin or placebo on intrapartum or postpartum infection incidence. We included studies evaluating women who had vaginal births as well as caesarean sections. Studies reporting maternal and neonatal infections were included in the current analysis. Review Manager 5.4 was used to analyse 6 randomized clinical trials involving 44,448 mothers and 44,820 newborns. The risk of bias of each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Primary outcomes included the incidence of maternal sepsis and all-cause mortality and neonatal sepsis and all-cause mortality; secondary outcomes included maternal (endometritis, wound and surgical site infections, chorioamnionitis, and urinary tract infections) and neonatal outcomes (infections of the eyes, ears and skin). A random-effects model was used to test for overall effects and heterogeneity. RESULTS: The pooled odds ratios (ORs) were as follows: 0.65 for maternal sepsis (95% CI, 0.55-0.77; I2, 0%; P < .00001); 0.62 for endometritis (95% CI, 0.52-0.74; I2, 2%; P < .00001); and 0.43 for maternal wound or surgical site infection (95% CI, 0.24-0.78; P < .005); however, there was great heterogeneity among the studies (I2, 75%). The pooled OR for pyelonephritis and urinary tract infections was 0.3 (95% CI, 0.17-0.52; I2, 0%; P < .0001), and that for neonatal skin infections was 0.48 (95% CI, 0.35-0.65; I2, 0%, P < .00001). There was no significant difference in maternal all-cause mortality or incidence of chorioamnionitis between the two groups. No significant differences were observed in the incidence of neonatal sepsis or suspected sepsis, all-cause mortality, or infections of the eyes or ears. CONCLUSION: In this meta-analysis, azithromycin use during labour reduced the incidence of maternal sepsis, endometritis, incisional infections and urinary tract infections but did not reduce the incidence of neonatal-associated infections, except for neonatal skin infections. These findings indicate that azithromycin may be potentially beneficial for maternal postpartum infections, but its effect on neonatal prognosis remains unclear. Azithromycin should be used antenatally only if the clinical indication is clear and the potential benefits outweigh the harms.

Multidrug-resistant conjugative plasmid carrying mphA confers increased antimicrobial resistance in Shigella.

Shigellosis remains a common gastrointestinal disease mostly in children < 5 years of age in developing countries. Azithromycin (AZM), a macrolide, is currently the first-line treatment for shigellosis in Bangladesh; ciprofloxacin (CIP) and ceftriaxone (CRO) are also used frequently. We aimed to evaluate the current epidemiology of antimicrobial resistance (AMR) and mechanism(s) of increasing macrolide resistance in Shigella in Bangladesh. A total of 2407 clinical isolates of Shigella from 2009 to 2016 were studied. Over the study period, Shigella sonnei was gradually increasing and become predominant (55%) over Shigella flexneri (36%) by 2016. We used CLSI-guided epidemiological cut-off value (ECV) for AZM in Shigella to set resistance breakpoints (zone-diameter ≤ 15 mm for S. flexneri and ≤ 11 mm for S. sonnei). Between 2009 and 2016, AZM resistance increased from 22% to approximately 60%, CIP resistance increased by 40%, and CRO resistance increased from zero to 15%. The mphA gene was the key macrolide resistance factor in Shigella; a 63MDa conjugative middle-range plasmid was harboring AZM and CRO resistance factors. Our findings show that, especially after 2014, there has been a rapid increase in resistance to the three most effective antibiotics. The rapid spread of macrolide (AZM) resistance genes among Shigella are driven by horizontal gene transfer rather than direct lineage.

Trends in Chlamydia trachomatis Treatment Prescribing Practices in King County, Washington, 2010-2018.

BACKGROUND: In 2021, national Chlamydia trachomatis (CT) treatment guidelines changed from recommending either azithromycin (1 g; single dose) or doxycycline (100 mg twice daily for 7 days) to recommending only doxycycline as first-line treatment. The distribution and trends in CT prescribing practices before the guidelines change is largely unknown. METHODS: We conducted a trends analysis using Washington STD surveillance data. We included all female cases of urogenital CT 15 years or older who resided in King County and were diagnosed between 2010 and 2018. Surveillance data included information on demographics, sexual history, clinical features, diagnosing facility (eg, emergency department, family planning), and treatment regimen. We conducted descriptive analyses to examine trends in prescribing practices over time and by facility type. We used Poisson regression to examine the association between CT case characteristics and receipt of receipt of azithromycin. RESULTS: There were 36,830 cases of female urogenital CT during the study period. The percent of cases receiving azithromycin increased significantly from 86% in 2010 to 94% in 2018; the percent receiving doxycycline decreased from 13% to 5%. Five of the 8 facility types prescribed azithromycin to >95% of CT cases by 2018. Cases who were younger or cases of color were more likely to receive azithromycin (versus doxycycline) compared with older and White cases, respectively. CONCLUSIONS: A substantial shift in CT prescribing practices will be needed to adhere to new CT treatment guidelines. Our findings highlight the need for targeted provider education and training to encourage the transition to doxycycline use.

Repeated imidocarb treatment failure suggesting emerging resistance of Babesia canis in a new endemic area in north-eastern Germany.

Canine babesiosis has been increasingly diagnosed in various regions of Germany such as north-eastern Germany in recent years. A dog with several relapses of Babesia canis infection after treatment with imidocarb is described. A 9-year-old male Magyar Viszla with B. canis infection was referred after two treatments with imidocarb (dosage 2.1 mg/kg SC) because of lethargy, fever and pancytopenia (additional treatments with prednisolone and doxycycline). Merozoites were detected in the blood smear and imidocarb treatment was repeated. Clinical signs, pancytopenia and a positive B. canis PCR occurred after the 3rd (6 mg/kg SC), 4th (7.7 mg/kg SC) and 5th (7.5 mg/kg SC and doxycycline for 4 weeks in addition) imidocarb injection and thorough tick prevention with isoxazoline and permethrin products. 12 days after the 5th injection, the PCR was negative for the first time. The dog was again presented with fever 35 days after the 5th injection. The B. canis PCR was positive and laboratory examination revealed pancytopenia. Treatment with atovaquone/azithromycin for 18 days was performed and no further relapse occurred for 32 weeks. In the case of suspected imidocarb resistance in B. canis infection, treatment with atovaquone/azithromycin can be an alternative.

Increased antimicrobial resistance against azithromycin during COVID: role of irrational utilization.

Objectives: To assess the use of azithromycin during coronavirus disease-2019 pandemic and its impact on antimicrobial resistance in an urban setting. METHODS: The retrospective, cross-sectional study was conducted on two different data sets. The first data set was of inpatients (N = 300) during the first wave of COVID 19 i.e. January to December, 2020. Data was collected from tertiary care hospitals in Karachi between October 2021 and November 2022 after approval from the ethics review committee of Ziauddin University, Karachi. Drug utilisation evaluation was done using a structured and validated tool. The treatment protocols were evaluated by comparing against the coronavirus disease-2019 treatment protocol 2020 and the guidelines issued by the Medical Microbiology and Infectious Diseases Society of Pakistan. Second data set comprised of the consumption data (obtained from pharmacies for both inpatients and outpatients) as well as the antimicrobial resistance, (obtained from antibiogram collected from the microbiology departments of the participating hospitals). This data was taken for the period of three years i.e. 2019 (Pre-COVID) to 2021 (Post-first wave of COVID) to establish trends of both consumption and antibiotic resistance. Data was analysed using SPSS 20. RESULTS: Of the 300 patients, 207(69%) were males and 93(31%) were females. There were 162(54%) adults with mean age 40.06±10.48 years, followed by 120(40%) geriatrics with mean age 70.37±6.94 years, 18(6%) paediatrics with mean age 13.5±3.60 years. All patients were given Azithromycin empirically followed by culture sensitivity test in 21% cases only. Comparison with COVID treatment protocols revealed the non-compliance of just 3%. However, in case of Community Acquired Pneumonia (CAP), sinusitis, typhoid and urethritis, comparison with MMIDSP guidelines revealed non-compliance of 95%, 22%, 75% and 100% respectively. Moreover, in 11% of patients, it was administered for conditions not recommended by guidelines. Furthermore, the Antibiogram exhibited percent increase in resistance against azithromycin. CONCLUSIONS: Enhanced consumption and irrational use of azithromycin during the coronavirus disease-2019 pandemic most likely contributed to increase in antimicrobial resistance.

Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial.

Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions. Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention. Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities. Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023. Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census. Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months. Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03676764.

Pythium insidiosum: In vitro oomicidal evaluation of telithromycin and interactions with azithromycin and amorolfine hydrochloride.

This study evaluated the repositioning of the ketolide antibacterial telithromycin (TLT) against the oomycete Pythium insidiosum and verified the combination of TLT and the antimicrobials azithromycin (AZM) and amorolfine hydrochloride (AMR), which have known anti-P. insidiosum activity. Susceptibility tests of P. insidiosum isolates (n = 20) against the drugs were carried out according to CLSI protocol M38-A2, and their combinations were evaluated using the checkerboard microdilution method. The minimum inhibitory concentrations were 0.5-4 µg/mL for TLT, 2-32 µg/mL for AZM, and 16-64 µg/mL for AMR. For the TLT+AZM combination, 52.75 % of interactions were indifferent, 43.44 % were antagonistic, and 9.70 % were synergistic. As for interactions of the TLT+AMR combination, 60.43 % were indifferent, 39.12 % were antagonistic, and 10.44 % synergistic interactions. This study is the first to evaluate the repositioning of the antibacterial TLT against mammalian pathogenic oomycetes, and our results show that its isolated action is superior to its combinations with either AZM or AMR. Therefore, we recommend including TLT in future research to evaluate therapeutic approaches in different clinical forms of human and animal pythiosis.

Real-world prescription of anti-COVID-19 drugs in hospitalized patients with COVID-19 in Japan.

OBJECTIVE: Prescription trends and patterns of anti-COVID-19 drugs in hospitalized patients were examined based on real world data to understand the use of anti-COVID-19 drugs in clinical practice in Japan. DESIGN: The longitudinal and cross-sectional study was conducted utilizing data from January 1, 2019 to December 31, 2021 of the MID-NET® medical information database, which stored the electronic medical records, administrative claim data, and diagnosis procedure combination data of patients in Japan. PARTICIPANTS: Hospitalized patients with a COVID-19-related diagnosis who received at least one anti-COVID-19 drug between April 1, 2020 and December 31, 2021. EXPOSURES: The following 14 drugs were included in this study: remdesivir, baricitinib, combination product of casirivimab and imdevimab, favipiravir, dexamethasone, ivermectin, azithromycin, nafamostat mesylate, camostat mesylate, ciclesonide, tocilizumab, sarilumab, combination product of lopinavir and ritonavir, and hydroxychloroquine. RESULTS: We identified 5,717 patients hospitalized with COVID-19 and prescribed at least one anti-COVID-19 drug. The entire cohort generally included patients over 41-50 years and more males. The most common prescription pattern was dexamethasone monotherapy (22.9%), followed by the concomitant use of remdesivir and dexamethasone (15.0%), azithromycin monotherapy (15.0%), remdesivir monotherapy (10.2%), and nafamostat mesylate monotherapy (8.5%). However, an often prescribed anti-COVID-19 drug differed depending on the period. CONCLUSIONS AND RELEVANCE: This study revealed the real-world situation of anti-COVID-19 drug prescriptions in hospitalized COVID-19 patients in Japan. A prescribed drug would depend on the latest scientific evidence, such as efficacy, safety, and approval status, at the time of prescription. Understanding the prescription of anti-COVID-19 drugs will be important for providing the most up-to-date treatments to patients and evaluating the benefit and/or risk of anti-COVID-19 drugs based on the utilization of an electronic medical record database.

Gut Microbiome Diversity and Antimicrobial Resistance After a Single Dose of Oral Azithromycin in Children: A Randomized Placebo-Controlled Trial.

Mass antibiotic distribution to preschool children resulted in alterations of the gut microbiome months after distribution. This individually randomized, placebo-controlled trial evaluated changes in the gut microbiome and resistome in children aged 8 days to 59 months after one dose of oral azithromycin in Burkina Faso. A total of 450 children were randomized in a 1:1 ratio to either placebo or azithromycin. Rectal samples were collected at baseline, 2 weeks, and 6 months after randomization and subjected to DNA deep sequencing. Gut microbiome diversity and normalized antimicrobial resistance determinants for different antibiotic classes were evaluated. Azithromycin decreased gut bacterial diversity (Shannon P < 0.0001; inverse Simpson P < 0.001) 2 weeks after treatment relative to placebo. Concurrently, the normalized abundance of macrolide resistance genetic determinants was 243-fold higher (95% CI: 76-fold to 776-fold, P < 0.0001). These alterations did not persist at 6 months, suggesting that disruptions were transient. Furthermore, we were unable to detect resistance changes in other antibiotic classes, indicating that co-resistance with a single course of azithromycin when treated at the individual level was unlikely.

2023 Korean sexually transmitted infections treatment guidelines for Mycoplasma genitalium by KAUTII.

The Korean Association of Urogenital Tract Infection and Inflammation and the Korea Disease Control and Prevention Agency updated the Korean sexually transmitted infections (STIs) guidelines to respond to the changing epidemiologic trends, evolving scientific evidence, and advances in laboratory diagnostics and research. The main recommendations in the Mycoplasma genitalium infection parts of the Korean STIs guidelines 2023 revision are as follows: 1) For initial treatment: azithromycin 500 mg orally in a single dose, then 250 mg once daily for 4 days. 2) In case of treatment failure or recurrence, a macrolide susceptibility/resistance test is required, when susceptibility/resistance test is not feasible, doxycycline or minocycline 100 mg orally twice daily for 7 days, followed by azithromycin 1 g orally on the first day, then azithromycin 500 mg orally once daily for 3 days and then a test-of-cure should be considered 3 weeks after completion of therapy. 3) In case of macrolide sensitivity, doxycycline or minocycline 100 mg orally twice daily for 7 days, followed by azithromycin 1 g orally initial dose, then azithromycin 500 mg orally once daily for 3 days. 4) In case of macrolide resistance, doxycycline or minocycline 100 mg orally twice daily for 7 days, followed by moxifloxacin 400 mg orally once daily for 7 days. In the Korean STIs guideline 2023, macrolide resistance-guided antimicrobial therapy was emphasized due to the increased prevalence of macrolide resistance worldwide. Therefore, in case of treatment failure or recurrence, a macrolide susceptibility/resistance test is required.

Azithromycin during Routine Well-Infant Visits to Prevent Death.

BACKGROUND: Mass distribution of azithromycin to children 1 to 59 months of age has been shown to reduce childhood all-cause mortality in some sub-Saharan African regions, with the largest reduction seen among infants younger than 12 months of age. Whether the administration of azithromycin at routine health care visits for infants would be effective in preventing death is unclear. METHODS: We conducted a randomized, placebo-controlled trial of a single dose of azithromycin (20 mg per kilogram of body weight) as compared with placebo, administered during infancy (5 to 12 weeks of age). The primary end point was death before 6 months of age. Infants were recruited at routine vaccination or other well-child visits in clinics and through community outreach in three regions of Burkina Faso. Vital status was assessed at 6 months of age. RESULTS: Of the 32,877 infants enrolled from September 2019 through October 2022, a total of 16,416 infants were randomly assigned to azithromycin and 16,461 to placebo. Eighty-two infants in the azithromycin group and 75 infants in the placebo group died before 6 months of age (hazard ratio, 1.09; 95% confidence interval [CI], 0.80 to 1.49; P = 0.58); the absolute difference in mortality was 0.04 percentage points (95% CI, -0.10 to 0.21). There was no evidence of an effect of azithromycin on mortality in any of the prespecified subgroups, including subgroups defined according to age, sex, and baseline weight, and no evidence of a difference between the two trial groups in the incidence of adverse events. CONCLUSIONS: In this trial conducted in Burkina Faso, we found that administration of azithromycin to infants through the existing health care system did not prevent death. (Funded by the Bill and Melinda Gates Foundation; CHAT ClinicalTrials.gov number, NCT03676764.).

Assessing prescription of antibiotics after vaccination against pneumococcal pneumonia; using prescription sequence symmetry analysis.

OBJECTIVES: Prescription sequence symmetry analysis (PSSA) is used to detect adverse event signals using administrative claims databases. In this study, we investigated whether PSSA can be applied to gauge the effects of PCV13 vaccination on antibiotic prescription rates in elderly patients. METHODS: We studied prescription records of patients aged 65 or older between 1 January 2014 and 31 December 2020, from the Helsana Swiss claims database. PSSA was performed to explore the relationship between 13-valent pneumococcal conjugate vaccine (PCV13) and six antibiotics recommended by the Swiss Society of Infectious Diseases for community-acquired pneumonia treatment (amoxicillin-clavulanate, azithromycin, clarithromycin, doxycycline, levofloxacin, and moxifloxacin), three additional antibiotics (amoxicillin, ciprofloxacin, and fosfomycin), and ten control drugs. RESULTS: Amoxicillin-clavulanate, clarithromycin, and levofloxacin were more likely to be prescribed before than after vaccination, for all time windows between 25 and 104 weeks. Adjusted sequence ratio (ASR) values ranged from 0.599 to 0.614, 0.508 to 0.568, and 0.514 to 0.752, respectively. Lower prescription rates after vaccination were also observed for azithromycin (all time windows between 38 and 104 weeks, ASR 0.705-0.739) and moxifloxacin (all time windows between 52 and 104 weeks, ASR 0.658-0.772). PCV13 did not have statistically significant associations with doxycycline, amoxicillin, ciprofloxacin, fosfomycin, or any of the ten controls. DISCUSSION: The lower prescription rate of antibiotics for community-acquired pneumonia after vaccination could be attributed to a protective effect of PCV13. This novel application of PSSA can be used to compare the real-world impact of other vaccines on drug consumption.

Antimicrobial Resistance of Genital Mycoplasma and Ureaplasma: A Multicentre Study Over a 5-Year Period in Italy (2017-2021).

Updated data on genital Mollicutes prevalence and antimicrobial susceptibility can help provide guidance for antibiotic stewardship and set up effective strategies for infection control policies. In this multicentre study, we assessed the prevalence and the resistance profile of Mycoplasma hominis (MH) and Ureaplasma species (U. parvum/U. urealyticum), analyzing data from 21,210 subjects who provided urogenital samples for Mollicutes detection by culture over a 5-year period (2017-2021) in two high-density urban areas in the North of Italy (i.e., Bologna and Lecco). Overall prevalence of Mollicutes infection was 22.3%, with women showing a significantly higher detection rate than men (p < 0.00001). The prevalence decreased with age (highest prevalence <30 years) and over the years considered. Ureaplasma strains were much more frequently detected (62.3%) compared to MH (8.3%) and to mixed infections (29.4%). Ureaplasma species showed high levels of ciprofloxacin resistance (39.5%), whereas MH strains were nonsusceptible to azithromycin and roxithromycin in about 60% of cases. Over time, a significant decrease of resistance to azithromycin and doxycycline was detected (p < 0.0001 and 0.0004, respectively), in parallel with an important increase of ciprofloxacin-resistance levels (p < 0.0001). Overall, our results revealed that minocycline and josamycin can be first-line drugs for Mollicutes empirical treatment.

Preventive and therapeutic effects of azithromycin on acrylamide-induced neurotoxicity in rats.

BACKGROUND: Acrylamide (ACR) can induce neurotoxicity through different pathways, including oxidative stress and apoptosis. Azithromycin is well-known for its antioxidant and anti-apoptotic properties. OBJECTIVE: To evaluate the potential neuroprotective effect of azithromycin in an in vivo model of ACR-induced neurotoxicity, by investigating its impact on oxidative stress and apoptosis pathways. METHODS: Male rats were divided into eleven groups at random (n = 6). 1:control (vehicle), 2:ACR (50 mg/kg, 11 days, I.P.), 3-7:ACR+ azithromycin (3.1, 6.25, 12.5, 25, 50 mg/kg, 11 days, I.P.), 8-9:ACR+ azithromycin (3.1, 6.25 mg/kg, from day 3-11), 10: ACR+ vitamin E (200 mg/kg, every other day, I.P.), 11. Azithromycin (50 mg/kg). Following the treatment period, a gait score examination was performed, and malondialdehyde (MDA), glutathione (GSH), Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio and caspase-3 levels in the cerebral cortex were measured. RESULTS: Gait abnormality, a drop in GSH, and an increase in lipid peroxidation, Bax/Bcl-2 ratio, and caspase-3 levels were all significantly triggered by ACR in the cerebral cortex versus the control group. Azithromycin 3.1 and 6.25 mg/kg with ACR and azithromycin 6.25 mg/kg with ACR from day 3-11 ameliorated movement disorders caused by ACR. Azithromycin in all doses and both protocols along with ACR decreased the MDA level. Azithromycin (3.1, 6.25 mg/kg) along with ACR in both protocols increased the level of GSH, reduced the Bax/Bcl-2 ratio and caspase-3 amounts in the brain tissue versus the ACR group. CONCLUSIONS: Administration of azithromycin had both preventive and therapeutic effects on ACR-induced neurotoxicity through its antioxidant and antiapoptotic properties.

Single-dose cefixime 800 mg plus doxycycline 100 mg twice a day for 7 days compared with single-dose ceftriaxone 1 g plus single-dose azithromycin 2 g for treatment of urogenital, rectal, and pharyngeal gonorrhoea: a randomised clinical trial.

OBJECTIVES: To evaluate the efficacy and tolerability of a single dose of oral cefixime 800 mg plus oral doxycycline 100 mg twice a day for 7 days, compared with a recommended single dose of ceftriaxone plus single dose of oral azithromycin, for treatment of uncomplicated urogenital, rectal, or pharyngeal gonorrhoea. METHODS: A noninferiority, open-label, multicentre randomized controlled trial was conducted in Prague, Czech Republic. Some 161 patients, 18-65 years of age diagnosed with uncomplicated urogenital, rectal, or pharyngeal gonorrhoea by nucleic acid amplification test (NAAT) were randomized to treatment with single dose of cefixime 800 mg plus doxycycline 100 mg twice a day for 1 week or a single dose of ceftriaxone 1 g intramuscularly plus single dose of azithromycin 2 g. The primary outcome was the number of participants with negative culture and NAAT at 1 week and 3 weeks, respectively, after treatment initiation. RESULTS: In all, 161 patients were randomized and 152 were included in per-protocol analyses. All 76 (100%; 95% CI, 0.95-1.00) patients treated with ceftriaxone plus azithromycin achieved negative cultures and NAAT after treatment. In the cefixime plus doxycycline arm at week 1, culture was negative in all 76 (100%) patients; at week 3, culture was negative in 70 of the 76 patients (92%; 95% CI, 0.84-0.97) and NAAT negative in 66 of the 76 patients (87%; 95% CI, 0.77-0.94). At week 3, culture and NAAT were negative in 65 of the 76 patients (86%; 95% CI, 0.76-0.93). Per-protocol risk difference was 14.5%; 95% CI, 6.56-22.38. All treatment failures observed in the cefixime arm were pharyngeal gonorrhoea cases. DISCUSSION: The combination of cefixime and doxycycline did not achieve noninferiority to ceftriaxone and azithromycin for treatment of gonorrhoea when including pharyngeal gonorrhoea. It did, however, show high efficacy for urogenital and rectal gonorrhoea.

[Bacterial Conjunctivitis: Current Aspects of Diagnosis and Therapy]. / Bakterielle Konjunktivitis: Aktuelle Aspekte der Diagnostik und Therapie.

Bacterial conjunctivitis is a leading cause of infectious conjunctivitis in children and second most common cause in adults. Although often self-limiting, it can lead to complications like corneal scarring and systemic infections in high-risk groups including newborns and immunocompromised patients. Thus, prompt diagnosis and treatment are essential for these vulnerable populations. Common bacterial causes are Staphylococcus aureus and Streptococcus pneumoniae in adults and Haemophilus influenzae and Moraxella catarrhalis in children. Clinical features alone do not reliably identify the causative pathogen. Microbiological testing is necessary for persistent or severe cases. Topical antibiotics like azithromycin or fluorochinolones are usually prescribed. However, gonococcal and chlamydial conjunctivitis warrant systemic antibiotics due to their potential for severe complications. Increasing antibiotic resistance might even necessitate tailored therapy based on antibiotic susceptibility profiles. Screening and treating pregnant women is an effective prevention strategy by reducing perinatal transmission (especially of gonococcal and chlamydial infections). In summary, while often self-limiting, potential complications and rising antibiotic resistance underscore the importance of timely diagnosis and treatment of bacterial conjunctivitis. Preventive measures including maternal screening are crucial public health initiatives to curb the risks associated with this common eye infection.

Emergence of high-level azithromycin-resistant Neisseria gonorrhoeae causing male urethritis in Johannesburg, South Africa, 2021.

BACKGROUND: In South Africa, Neisseria gonorrhoeae , which is the predominant cause of male urethritis, is treated syndromically using dual ceftriaxone and azithromycin therapy. We determined antimicrobial susceptibilities of N. gonorrhoeae isolates from urethral discharge specimens, and genetically characterised those with elevated minimum inhibitory concentrations (MICs) for first-line antimicrobials. METHODS: Routine antimicrobial susceptibility testing (AST) of N. gonorrhoeae isolates included E-test for ceftriaxone, cefixime and gentamicin and agar dilution for azithromycin and spectinomycin. Neisseria gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) was performed for isolates with elevated MICs to identify antimicrobial resistance (AMR) determinants, and Neisseria gonorrhoeae Multi-Antigen Sequence Typing (NG-MAST) was used to determine strain relatedness. RESULTS: N. gonorrhoeae was cultured from urethral discharge swab specimens obtained from 196 of 238 (82.4%) men presenting to a primary healthcare facility in Johannesburg in 2021. All viable isolates were susceptible to extended-spectrum cephalosporins. Four isolates had high azithromycin MICs ranging from 32mg/L to >256mg/L and grouped into two novel NG-MAST and NG-STAR groups. Two isolates from Group 1 (NG-MAST ST20366, NG-STAR ST4322) contained mutated mtrR (G45D) and 23S rRNA (A2059G) alleles, while the two isolates from Group 2 (NG-MAST ST20367, NG-STAR ST4323) had different mutations in mtrR (A39T) and 23S rRNA (C2611T). CONCLUSIONS: We report the first cases of high-level azithromycin resistance in N. gonorrhoeae from South Africa. Continued AMR surveillance is critical to detect increasing azithromycin resistance prevalence in N. gonorrhoeae , which may justify future modifications to the STI syndromic management guidelines.