OBJECTIVE: There were 82.4 million new gonorrhoea cases worldwide in 2020. Dual treatment with ceftriaxone or cefixime and azithromycin or doxycycline is currently recommended for gonorrhoea in Indonesia. However, reduced susceptibility and resistance to cephalosporins and azithromycin are increasing. We evaluated the susceptibility pattern of Neisseria gonorrhoeae to cefixime, ceftriaxone, azithromycin and doxycycline.
METHODS: N. gonorrhoeae isolates were obtained from 19 male participants with clinically and laboratory-confirmed gonorrhoea. Antibiotic susceptibility testing was conducted by disc diffusion and interpreted according to Clinical and Laboratory Standards Institute and Centers for Disease Control and Prevention criteria.
RESULTS: Reduced susceptibility or resistance was observed against doxycycline in 19 isolates (100%), cefixime in six (31.6%), ceftriaxone in three (15.8%) and azithromycin in zero (0%) isolates.
CONCLUSIONS: A dual treatment regimen with ceftriaxone and azithromycin can still be recommended as first-line therapy for gonorrhoea in Indonesia. Antibiotic susceptibility surveillance of N. gonorrhoeae should be routinely conducted.

UNASSIGNED: This study aims to examine the frequency of Salmonella Paratyphi found in blood cultures and evaluate the antibiotic susceptibility pattern of Salmonella isolates to different antibiotics. Additionally, the study aims to assess the paradigm shift in the trend of enteric fever caused by Salmonella Typhi (S. Typhi) to Salmonella Paratyphi(S. Paratyphi) .
UNASSIGNED: Retrospective study.
UNASSIGNED: The study enrolled patients aged 12 years and above diagnosed with enteric fever (positive blood culture) and admitted to Peelamedu Samanaidu Govindasamy Naidu (PSG) Hospital.
UNASSIGNED: The study analyzed demographic and antibiotic susceptibility profiles of Salmonella isolates collected from 106 enteric fever patients in the hospital between 2010 and 2022. The susceptibility profiles of Salmonella isolates to multiple antibiotics were assessed.
UNASSIGNED: There were 106 participants, and 95 (89.62%) of them had enteric fever linked to Salmonella Typhi, while only 11 (10.38%) had enteric fever linked to Salmonella Paratyphi A. From 2010 to 2022, the study discovered a general decline in the prevalence of enteric fever caused by Salmonella species. But between 2014 and 2022, the incidence of enteric fever linked to S. Typhi rapidly increased. Azithromycin (100% , n = 106) and ceftriaxone (99% , n = 105) were highly effective against the Salmonella isolates, whereas nalidixic acid was resisted by 3 isolates (4.72%, n = 3).
UNASSIGNED: The study observed a higher incidence of Salmonella Typhi in comparison to Paratyphi A and a greater susceptibility of males to enteric fever.
UNASSIGNED: None declared.

BACKGROUND: An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy.
METHODS: This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord\' test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations.
RESULTS: A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low.
CONCLUSIONS: This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.

The photodegradation of azithromycin present was carried out in water using H2O2 under UV irradiation. The reaction variables considered in this study were the amount of H2O2 solution and the initial concentration of azithromycin to evaluate the performance of the photodegradation process. The azithromycin degradation was not observed in the dark during stirring for 20 min. The study showed an efficient photodegradation of azithromycin using H2O2 as an oxidant in the presence of UV irradiation. The azithromycin degradation was altered significantly by the pH of the irradiated solution. The degradation was low at an acidic pH and showed an increasing trend as the pH changed to basic. The azithromycin degradation increased with a higher amount (higher concentration) of H2O2. The degradation of azithromycin decreased with a higher concentration of azithromycin in the reacting solution. The highest degradation of AZT was achieved in 1 h using a 1.0 ppm AZT solution containing 3 mL of H2O2. The experimental data obtained were well-fitted to zero-order reaction kinetics. The results of this study were found quite excellent. They showed 100% degradation in 1 h when compared with those reported in the literature, both with photocatalysis using nanomaterials and photolysis using light irradiation and/or H2O2. The UV/H2O2 system was found to be quite efficient for the photodegradation of azithromycin, and this system can be applied to degrade other organic pollutants present in industrial wastewater.

BACKGROUND: Maternal undernutrition is a direct risk factor for infant growth faltering.
OBJECTIVE: We evaluated the effect of postnatal Balanced Energy Protein (BEP) supplementation in lactating women and Azithromycin (AZ) in infants on infant growth outcomes.
METHODS: A randomized controlled superiority trial of lactating mother-newborn dyads was conducted in Karachi, Pakistan. Mothers intending to breastfeed their newborns with mid-upper arm circumference of less than 23 cm and live infants between 0-6 days of life were randomly assigned to one of three arms in a 1:1:1 ratio. Lactating mothers in the control arm received standard-of-care counseling on exclusive breastfeeding, nutrition, infant immunization and health promotion plus iron-folate supplementation until the infant was 6 months of age. In intervention arm 1, mothers additionally received two 75-gram sachets of BEP per day, while in intervention arm 2 along with the standard-of-care and BEP, the infant also received one dose of Azithromycin (at 20 mg per kilogram) at 42 days of life. The primary outcome was infant length velocity at 6 months. The total sample size was 957 (319 in each arm).
RESULTS: From August 1, 2018 to May 19, 2020, 319 lactating mother-newborn dyads were randomized in each arm, and the last follow-up was completed on November 20, 2020. The mean difference in length velocity (cm per month) between BEP alone and control was 0.01 (95% CI: -0.03, 0.06), BEP plus AZ and control was 0.08 (95% CI:0.03,0.13) and between BEP+AZ and BEP alone was 0.06 (95% CI: 0.01, 0.11). There were 1.46% (14/957) infant deaths in the trial, and 17.9% (171/957) non-fatal events (injectable treatment and/or hospitalizations) were recorded.
CONCLUSIONS: Postnatal maternal BEP supplementation and infant AZ administration could modestly improve infant growth outcomes at 6 months, suggesting potential benefits in simultaneously addressing maternal and infant undernutrition.
UNASSIGNED: This trial is registered on ClinicalTrials.gov NCT03564652 on June 21, 2018.

Bacteria are involved in numerous interactions during infection and among host-associated microbial populations. Salmonella enterica serovar Typhimurium is a foodborne pathogen of great importance as well as a model organism to study interactions within a microbial community. In this study, we found that S. Typhimurium becomes tolerant to azithromycin when co-cultured with lactobacilli strains. Similarly, acidified media, from cell-free supernatant of lactobacilli cultures for instance, also induced the tolerance of S. Typhimurium to azithromycin. The addition of membrane disruptors restored the normal sensitivity to azithromycin in acidified media, but not when lactobacilli were present. These results suggested that the acidification of the media led to modification in envelope homeostasis, but that a different mechanism promoted the tolerance to azithromycin in the presence of lactobacilli strains. To further understand how lactobacilli strains modify the sensitivity of S. Typhimurium to azithromycin, a high-throughput assay was performed using the single-gene deletion collection of the S. Typhimurium (1) in co-culture with Lacticaseibacillus rhamnosus and (2) in sterile acidic conditions (pH 5.5 media only). As expected, both screens identified genes involved in envelope homeostasis and membrane permeability. Our results also suggest that changes in the metabolism of S. Typhimurium induce the tolerance observed in the presence of L. rhamnosus. Our results thus highlight two different mechanisms by which lactobacilli induce the tolerance of S. Typhimurium to azithromycin.IMPORTANCEThis study provides valuable insights into the intricate interactions between bacteria during infections and within host-associated microbial communities. Specifically, it sheds light on the significant role of lactobacilli in inducing antibiotic tolerance in Salmonella enterica serovar Typhimurium, a critical foodborne pathogen and model organism for microbial community studies. The findings not only uncover the mechanisms underlying this antibiotic tolerance but also reveal two distinct pathways through which strains of lactobacilli might influence Salmonella\'s response to antibiotics. Understanding these mechanisms has the potential to enhance our knowledge of bacterial infections and may have implications for the development of strategies to combat antibiotic resistance in pathogens, such as Salmonella. Furthermore, our results underscore the necessity to explore beyond the direct antimicrobial effects of antibiotics, emphasizing the broader microbial community context.

Azithromycin can result in severe cholestatic liver disease. We describe two cases of intractable pruritus secondary to drug-induced cholestatic liver injury, unresponsive to symptomatic medical therapy, necessitating and responding well to therapeutic plasma exchange (TPE). The first is a case of a 60-year-old male known to have stable chronic lymphocytic leukemia (CLL) and benign prostatic hyperplasia, and the second is a 46-year-old female known to have primary biliary cirrhosis (PBC) who presented at six weeks and two weeks, respectively, post-mild-COVID-19 pneumonia. Their drug histories were positive for over-the-counter (OCT) azithromycin use during the COVID-19 pneumonia period. They presented with a two-week history of severe itching, associated with sleep deprivation and impaired quality of life. Liver function tests revealed a cholestatic pattern of liver injury. Pruritus remained refractory to multiple lines of treatment including bile acid sequestrants and antihistamines. Rapid and long-lasting relief of the patient\'s symptoms was observed after three sessions of TPE. Our cases highlight medically recalcitrant cholestatic pruritus as an adverse effect of antibiotic misuse during the recent COVID-19 pandemic. Sustained symptomatic improvements were seen after TPE.

This study investigates the incorporation of block natural rubber (NR) as a viscosity-inducing agent in NR oily liquids designed for drug delivery systems. A variety of liquids, encompassing natural oils, synthetic and non-oil liquids, and a eutectic mixture, were incorporated with NR using solvent displacement technique. Successful formulations were achieved for several oily liquids, with viscosity correlating to NR concentration. Particularly, a eutectic mixture of menthol and camphor exhibited optimal viscosity by direct dissolving enabling the development of transdermal ibuprofen delivery and injectable azithromycin for periodontitis treatment. NR prolonged the release of both drugs. The extended-release ibuprofen system holds promise for transdermal applications, while the azithromycin system displayed inhibitory effects against Staphylococcus aureus, Streptococcus mutans, and Porphyromonas gingivalis, suggesting potential for periodontitis treatment. Overall, this investigation advances the development of NR oily liquids as a versatile drug delivery system that can be applied both on the skin and for the local injection into the periodontal pocket, showcasing promise for various therapeutic applications.

BACKGROUND: Azithromycin (AZM) has been proposed as a potential therapeutic drug in acute pulmonary injury due to its immunomodulatory and anti-inflammatory properties. However, its therapeutic mechanism remains not fully understood.
METHODS: LPS was used to stimulate MLE-12 cells and RAW264.7 macrophages. Analyses of viability and apoptosis were performed by CCK-8 assay and flow cytometry, respectively. Protein analysis was performed by immunoblotting, and mRNA expression was tested by quantitative PCR. The secretion levels of TNF-α and IL-6 were detected by ELISA. MDA, GSH, ROS and Fe2+ contents were analyzed using assay kits.
RESULTS: Administration of AZM or depletion of methyltransferase-like 3 (Mettl3) could attenuate LPS-triggered apoptosis, inflammation and ferroptosis in MLE-12 alveolar cells, as well as enhance M2 polarization of LPS-stimulated RAW264.7 macrophages. In LPS-exposed MLE-12 and RAW264.7 cells, AZM reduced Mettl3 protein expression and inactivated the NF-κB signaling through downregulation of Mettl3. Furthermore, Mettl3 restoration abated AZM-mediated anti-apoptosis, anti-inflammation and anti-ferroptosis effects in LPS-exposed MLE-12 cells and reversed AZM-mediated M2 polarization enhancement of LPS-exposed RAW264.7 macrophages.
CONCLUSIONS: Our study indicates that AZM can promote M2 polarization of LPS-exposed RAW264.7 macrophages and attenuate LPS-triggered injury of MLE-12 alveolar cells by inactivating the Mettl3-mediated NF-κB pathway.

BACKGROUND: Budesonide, capable of reducing vascular permeability, suppressing mucus secretion, and alleviating edema and spasms, is widely used in China for combined infectious disease treatment. This study assesses budesonide\'s efficacy and safety as an adjunct to azithromycin in pediatric Mycoplasma pneumonia management in China, aiming to establish a strong theoretical foundation for its clinical application.
METHODS: We conducted a comprehensive search for qualifying studies across 5 English databases and 4 Chinese databases, covering publications until October 31, 2023. Endpoint analyses were performed using standard software (Stata Corporation, College Station, TX). This study was conducted in compliance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
RESULTS: A total of 24 randomized controlled trials were involved in the current study, including 2034 patients. Our findings indicate that the combination of budesonide with azithromycin for the treatment of pediatric Mycoplasma pneumonia delivers superior therapeutic efficacy (Intravenous: odds ratio [OR], 0.156, P < .001; Sequential: OR, 0.163, P = .001; Oral: OR, 0.139, P < .001), improved pulmonary function (Forced expiratory volume in 1 second: weighted mean differences [WMD], -0.28, P = .001; Peak expiratory flow: WMD, -0.554, P = .002; Forced vital capacity: WMD, -0.321, P < .001), diminished lung inflammation (IL-6: WMD, 4.760, P = .002; c-reactive protein: WMD, 5.520, P < .001; TNF-α: WMD, 9.124, P < .001), reduced duration of fever, faster resolution of cough and rales, all without increasing the occurrence of adverse events.
CONCLUSIONS: The combination of budesonide and azithromycin demonstrates enhanced therapeutic effectiveness, promotes improved pulmonary function, shortens the duration of symptoms, and effectively mitigates the overexpression of inflammatory factors like c-reactive protein, TNF-α, and IL-6, all without an associated increase in adverse reactions in pediatric mycoplasma pneumonia.