The Potentiation Activity of Azithromycin in Combination with Colistin or Levofloxacin Against Pseudomonas aeruginosa Biofilm Infection.

Objective: Pseudomonas aeruginosa (PA) often displays drug resistance and biofilm-mediated adaptability. Here, we aimed to evaluate the antibiofilm efficacy of azithromycin-based combination regimens. Methods: Minimum inhibitory concentrations (MICs), minimal biofilm eradication concentrations (MBECs), and MBEC-combination of azithromycin, colistin, amikacin, and levofloxacin to bioluminescent strain PAO1 and carbapenem-resistant PAO1 (CRPAO1) were assessed. An animal biofilm infection model was established and detected using a live animal bio-photonic imaging system. Results: In vitro, PAO1 and CRPAO1 were susceptible to colistin, amikacin, and levofloxacin, while they were unsusceptible to azithromycin. The combinations based on azithromycin have no synergistic effect on biofilm in vitro. In vivo, azithromycin plus colistin or levofloxacin could shorten the PAO1 biofilm eradication time, which totally eradicates the biofilm in all mice on the 8th or 6th day, while monotherapy only eradicate biofilm in 70% or 80% mice on the 8th day. For CRPAO1 biofilm, only azithromycin-colistin combination and colistin monotherapy eradicated the bacteria in 60% and 40% of mice at the 6th day. Conclusion: Azithromycin-based combinations containing levofloxacin or colistin had no synergistic effect in vitro, and they are promising for clinical applications due to the good synergistic activity against PAO1 biofilms in vivo.

Safety and Pharmacokinetics of a Ciprofloxacin and Azithromycin Stent for Chronic Rhinosinusitis.

OBJECTIVES: Previously, we developed a novel double-coated sinus stent containing ciprofloxacin (inner layer) and azithromycin (outer layer) (CASS), but released drug concentrations were found to be insufficient for clinical usage. Our objectives are to improve drug release of CASS and assess safety and pharmacokinetics in rabbits. METHODS: Dip coating was used to create the CASS with 2 mg ciprofloxacin and 5 mg azithromycin. A uniformed double coating was assessed with scanning electron microscopy (SEM), and the release patterns of both drugs and lactate dehydrogenase (LDH) assay were evaluated over 14 days in vitro. Safety, tolerability, and pharmacokinetics of the CASS were tested in rabbits through insertion into the maxillary sinus and evaluated with nasal endoscopy, CT scans, histology, blood counts and chemistries, and in vivo drug release. RESULTS: SEM confirmed the uniformity of the dual coating of ciprofloxacin and azithromycin, and thickness (µm) was found to be 14.7 ± 2.4 and 28.1 ± 4.6, respectively. The inner coated ciprofloxacin showed a sustained release over 14 days (release %) when soaked in saline solution (day 7, 86.2 ± 3.4 vs. day 14,99.2 ± 5.1). In vivo analysis showed that after 12 days, 78.92 ± 7.67% of CP and 84.12 ± 0.45% of AZ were released into the sinus. There were no significant differences in body weight, white blood cell counts, and radiographic changes before and after CASS placement. No significant histological changes were observed compared to the contralateral control side. CONCLUSION: Findings suggest that the CASS is an effective method for delivering therapeutic levels of antibiotics. Further studies are needed to validate efficacy in a preclinical sinusitis model. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Azithromycin and moxifloxacin resistance determinants in Mycoplasma genitalium in Lleida, Spain.

OBJECTIVE: Mycoplasma genitalium (MG) is a microorganism related to sexually transmitted infections. Antibiotic resistance of MG leads to an increase in treatment failure rates and the persistence of the infection. The aim of this study was to describe the most frequent mutations associated with azithromycin and moxifloxacin resistance in our geographical area. METHODS: A prospective study from May 2019 to May 2023 was performed. MG-positive samples were collected. Real-time PCRs (AllplexTM MG-AziR Assay and AllplexTM MG-MoxiR Assay, Seegene) were performed in MG positive samples to detect mutations in 23S rRNA V domain and parC gene. RESULTS: A 37.1% of samples presented resistance determinants to azithromycin and the most common mutation detected was A2059G (57.9%). Resistance to moxifloxacin was studied in 72 azithromycin-resistant samples and 36.1% showed mutations, being G248T the most prevalent (73.1%). CONCLUSIONS: The resistance to different lines of treat ment suggests the need for a targeted therapy and the performing of a test of cure afterwards.

Increased susceptibility to azithromycin of Pseudomonas aeruginosa biofilms using RPMI 1640 testing media.

Azithromycin (AZM) is efficient for treatment of chronic Pseudomonas aeruginosa biofilm lung infections, despite of resistance in conventional susceptibility testing. It has been shown that planktonic P. aeruginosa are more susceptible to AZM when tested in RPMI 1640 medium. The aim of the study was to test the susceptibility to AZM of P. aeruginosa biofilms in LB vs RPMI 1640 media. We investigated the effect of AZM on planktonic and biofilms of (WT) P. aeruginosa (PAO1), the hypermutable (ΔmutS) and the antibiotic-resistant phenotype(ΔnfxB) mutants. The effect of AZM on young and mature biofilms was investigated in the modified Calgary Biofilm Device by estimation of the minimal biofilm inhibitory concentration (MBIC). The AZM MBIC90 in LB/RPMI1640 on young biofilms treated for 24 h was 16/4 µg/mL for PAO1, 32/8 µg/mL for ΔmutS, and 256/16 µg/mL for ΔnfxB, while in mature biofilms was 256/2 µg/mL for PAO1 and ΔmutS and 16/1 µg/mL for ΔnfxB. The effect of AZM was improved when the treatment was prolonged to 72 h, supporting the intracellular accumulation of AZM. An increased susceptibility of P. aeruginosa biofilms to AZM was observed in RPMI 1640 than in LB medium. Our results might improve susceptibility testing and dosing of AZM for treatment of biofilm infections.

The metabolic footprint of Vero E6 cells highlights the key metabolic routes associated with SARS-CoV-2 infection and response to drug combinations.

SARS-CoV-2 burdens healthcare systems worldwide, yet specific drug-based treatments are still unavailable. Understanding the effects of SARS-CoV-2 on host molecular pathways is critical for providing full descriptions and optimizing therapeutic targets. The present study used Nuclear Magnetic Resonance-based metabolic footprinting to characterize the secreted cellular metabolite levels (exometabolomes) of Vero E6 cells in response to SARS-CoV-2 infection and to two candidate drugs (Remdesivir, RDV, and Azithromycin, AZI), either alone or in combination. SARS-CoV-2 infection appears to force VE6 cells to have increased glucose concentrations from extra-cellular medium and altered energetic metabolism. RDV and AZI, either alone or in combination, can modify the glycolic-gluconeogenesis pathway in the host cell, thus impairing the mitochondrial oxidative damage caused by the SARS-CoV-2 in the primary phase. RDV treatment appears to be associated with a metabolic shift toward the TCA cycle. Our findings reveal a metabolic reprogramming produced by studied pharmacological treatments that protects host cells against virus-induced metabolic damage, with an emphasis on the glycolytic-gluconeogenetic pathway. These findings may help researchers better understand the relevant biological mechanisms involved in viral infection, as well as the creation of mechanistic hypotheses for such candidate drugs, thereby opening up new possibilities for SARS-CoV-2 pharmacological therapy.

Short-term azithromycin use is associated with QTc interval prolongation in children with cystic fibrosis.

BACKGROUND: Azithromycin is used for children with cystic fibrosis (CF) for its immunomodulatory and anti-inflammatory action. This study investigated the short-term alterations in QTc interval associated with azithromycin prophylaxis in pediatric patients with CF. METHODS: This study included 121 patients with mild CF, of whom 76 received azithromycin (patient group) and 45 did not receive azithromycin (control group). The patient and control groups were categorized according to age as under 12 years of age and over 12 years of age. The first presentation measured all the patient and control groups at basic QTc time intervals. The QTc intervals of all patients were then remeasured systemically at 1, 3, and 6 months. Age categories and QTc intervals that were calculated at each month in the patient and control groups were compared statistically. RESULTS: A statistically significant difference was detected in the patient group between the initial QTc interval time and the electrocardiogram (ECG) findings in the first and third months after prophylaxis treatment (p < 0.001; p = 0.01). However, no statistically significant difference was detected in the sixth month (p > 0.05) in all groups. Almost all of the children's QTc intervals were within normal range and within the safety zone (under 0.44 s). No statistically significant difference was detected in the control group between the initial ECG and the QTc intervals measured at 1, 3, and 6 months. CONCLUSION: Short-term use of azithromycin prophylaxis in pediatric patients with mild CF slightly increased the QTc interval in the first and third months of follow-up. Nevertheless, all QTc interval changes fell within the safety zone. Notably, 1 month of follow-up treatment should be performed to check for any alteration in the QTc interval. If increased QTc interval duration is not detected in the first month, azithromycin prophylaxis can be safely prescribed.

Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin, and Amoxicillin.

Background: Prior research has raised concerns regarding the use of macrolides and their association with an increased risk of cardiovascular events. Methods: We conducted a cohort study, where we explored the cardiovascular risks associated with the treatment of COPD patients using macrolide antibiotics-namely azithromycin, clarithromycin, and roxithromycin-with amoxicillin serving as a reference. The study focused on COPD patients in an outpatient setting and included a thorough 3-year follow-up. Patients were categorized into four groups based on their treatment. The primary analysis utilized an adjusted Cox model, supplemented by sensitivity analysis through inverse probability of treatment weighting. Results: No significant differences were found in major adverse cardiovascular events (MACE-stroke, acute myocardial infarction, cardiovascular death) between the macrolide groups, and the amoxicillin/hazard ratios (HR) were azithromycin HR = 1.01, clarithromycin HR = 0.99, and roxithromycin HR = 1.02. Similarly, sensitivity analysis showed no disparities in all-cause mortality and cardiovascular death among the groups. Conclusions: Overall, the study revealed no evidence of increased risk of MACE, all-cause mortality, or cardiovascular death in COPD patients treated with these macrolides compared to amoxicillin over a 3-year period.

Quercetin of huoxuehuayu tongluo decoction and azithromycin combination therapy effectively improves rat tubal factor infertility by inhibiting inflammation.

Objectives: Tubal factor infertility (TFI) is common female infertility responsible for a large portion of female factor infertility. This study reveals the effect of the quercetin of Huoxuehuayu Tongluo Decoction with azithromycin on the pregnancy rate and inflammation of TFI female rats. Materials and Methods: Female Sprague Dawley rats were constructed into the TFI model and treated with quercetin, Huoxuehuayu Tongluo Decoction, and combination therapy (quercetin and azithromycin). Pregnancy rate and litter size were measured. Network pharmacology was applied to analyze the interaction between Huoxuehuayu Tongluo Decoction and TFI. The combination of quercetin and IL-6 was analyzed by molecular docking. HE staining and electron microscopy were used to observe the histopathology and ultrastructure of fallopian tube tissues. The TNF-α, IL-1ß, IL-6, IL-8, and MPO levels were detected by ELISA. The activation of JAK/STAT, MAPK, and NF-κB p65 pathways was detected by western blot or immunohistochemistry. Results: Quercetin was the main active component of Huoxuehuayu Tongluo Decoction, and could bind to IL-6 in TFI. Target genes were enriched in the IL-17 signaling pathway, JAK-STAT signaling pathway, inflammatory disease, etc. Under the quercetin and azithromycin combination therapy, both rat pregnancy rates and litter sizes increased significantly. quercetin and azithromycin alleviated the symptoms of hydrosalpinx and inflammatory damage in fallopian tube tissues. The phosphorylation of JAK/STAT and MAPK pathways and NF-κB p65 translocation to the nucleus were significantly inhibited by the quercetin and azithromycin therapy. Conclusion: Quercetin and azithromycin combination therapy inhibited inflammation and phosphorylation of JAK/STAT and MAPK pathways to improve TFI inflammation and pregnancy function.

A systematic review of Neisseria gonorrhoeae drug resistance development in South Africa.

In South Africa, basic healthcare centres treat sexually transmitted infections (STIs) using a syndromic approach. In line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a complete study of all randomised controlled trials and surveillance data relevant to N. gonorrhoeae antibiotic resistance was conducted. To discover papers published between 2002 and 2022, searches were undertaken using PubMed, EMBASE and any other relevant databases. This systematic review extracted a total of 463 articles published between 2002 and 2022 from a variety of online research sources. Seven South African provinces were represented in the studies that were assessed. Mpumalanga and the North West Province did not have any studies that described the identification and monitoring of antimicrobial resistance (AMR). This study presents data obtained from a comprehensive analysis of 2140 isolates, in which we examined the presence of one or more antibiotic resistance. Our findings revealed that out of these samples, 1891 isolates exhibited antimicrobial properties; tetracycline was the antimicrobial resistance that was found the most often (30%), followed by ciprofloxacin (19%) and penicillin (17%). The mean of the isolates was 143, the upper 95% mean was 243, and the standard deviation (SD) was 181.6. All microbiological identification and susceptibility testing processes must be standardised and improved so national organisations can monitor AMR. The nation's health community must address all identified areas of concern to avoid AMR.

High cure rates of Mycoplasma genitalium following empiric treatment with azithromycin alongside frequent detection of macrolide resistance in Austria.

BACKGROUND: Mycoplasma genitalium (MG) is an emerging sexually transmitted infection, often harboring resistance-associated mutations to azithromycin (AZM). Global surveillance has been mandated to tackle the burden caused by MG, yet no data are available for Austria. Thus, we aimed to investigate the prevalence of MG, disease characteristics, and treatment outcomes at the largest Austrian HIV-and STI clinic. METHODS: All MG test results at the Medical University of Vienna from 02/2019 to 03/2022 were evaluated. Azithromycin resistance testing was implemented in 03/2021. RESULTS: Among 2671 MG tests, 199 distinct and mostly asymptomatic (68%; 135/199) MG infections were identified, affecting 10% (178/1775) of all individuals. This study included 83% (1479/1775) men, 53% (940/1775) men who have sex with men (MSM), 31% (540/1754) HIV+, and 15% (267/1775) who were using HIV pre-exposure prophylaxis (PrEP). In logistic regression analysis, 'MSM' (aOR 2.55 (95% CI 1.65-3.92)), 'use of PrEP' (aOR 2.29 (95% CI 1.58-3.32)), and 'history of syphilis' (aOR 1.57 (95% CI 1.01-2.24) were independent predictors for MG infections. Eighty-nine percent (178/199) received treatment: 11% (21/178) doxycycline (2 weeks), 52% (92/178) AZM (5 days), and 37% ( 65/178) moxifloxacin (7-10 days) and 60% (106/178) had follow-up data available showing negative tests in 63% (5/8), 76% (44/58) and 85% (34/40), respectively. AZM resistance analysis was available for 57% (114/199)) and detected in 68% (78/114). Resistance-guided therapy achieved a cure in 87% (53/61), yet, empiric AZM-treatment (prior to 03/2021) cleared 68% (26/38). CONCLUSIONS: Mycoplasma genitalium was readily detected in this Austrian observational study, affected predominantly MSM and often presented as asymptomatic disease. We observed a worryingly high prevalence of AZM resistance mutations; however, empiric AZM treatment cleared twice as many MG infections as expected.

Antimicrobial macrozones interact with biological macromolecules via two-site binding mode of action: Fluorimetric, NMR and docking studies.

Macrozones are novel conjugates of azithromycin and thiosemicarbazones, which exhibit very good in vitro antibacterial activities against susceptible and some resistant bacterial strains thus showing a potential for further development. A combination of spectrometric (fluorimetry, STD and WaterLOGSY NMR) and molecular docking studies provided insights into atomic details of interactions between selected macrozones and biological receptors such as E. coli ribosome and bovine serum albumin. Fluorimetric measurements revealed binding constants in the micro-molar range while NMR experiments provided data on binding epitopes. It has been demonstrated that both STD and WaterLOGSY gave comparable and consistent results unveiling atoms in intimate contacts with biological receptors. Docking studies pointed towards main interactions between macrozones and E. coli ribosome which included specific π - π stacking and hydrogen bonding interactions with thiosemicarbazone part extending down the ribosome exit tunnel. The results of the docking experiments were in fine correlation with those obtained by NMR and fluorimetry. Our investigation pointed towards a two-site binding mechanism of interactions between macrozones and E. coli ribosome which is the most probable reason for their activity against azithromycin-resistant strains. Much better activity of macrozone-nickel coordinated compound against E. coli ribosome compared to other macrozones has been attributed to the higher polarity which enabled better bacterial membrane penetration and binding of the two thiosemicarbazone units thus additionally contributing to the overall binding energy. The knowledge gained in this study should play an important role in anti-infective macrolide design in the future.

Comparison of a single-dose vectored thermal pulsation procedure with 5-day course of daily oral azithromycin for meibomian gland dysfunction.

PURPOSE: This study aims at comparing the efficacy of a single-dose vectored thermal pulsation (VTP) procedure versus 5 days once daily oral azithromycin in patients with meibomian gland disease (MGD) by measuring the symptomatology and ocular surface parameters. MATERIALS AND METHODS: The study was conducted as a prospective, nonrandomized, comparative study over a period of 17 months at a tertiary care center. In this study, 60 patients with MGD were enrolled after they gave their informed consent according to the inclusion-exclusion criteria and were divided into two groups, 30 each in the azithromycin group and the VTP, i.e., the LipiFlow group. One group was treated with oral azithromycin for 5 days and the other group was given LipiFlow treatment. Postprocedure, follow-up was done for 2 weeks, 3 months, and 6 months. RESULTS: A statistically significant difference was noted in the score Standard Patient Evaluation of Eye Dryness questionnaire after 3 months of treatment in both the azithromycin and LipiFlow group (P < 0.0001), and the LipiFlow group showed sustained improvement at 6-month follow-up as score improved to 8.83 ± 2.32, whereas it deteriorated in azithromycin group to 13.77 ± 1.65. Pretreatment Ocular Surface Disease Index score (P = 0.126) and posttreatment (P < 0.0001) showed significant differences in both groups. The LipiFlow group showed an improved score of 25.65 ± 6.11 after 6 months of treatment, whereas it deteriorated to 34.79 ± 4.98 in the azithromycin group. Pretreatment, tear film break-up time (P = 0.28) and 6 months posttreatment score (P < 0.0001) showed significant differences in both groups, but in the LipiFlow group, it improved to 15.30 ± 1.76 after 6 months, whereas in the azithromycin group, it was 10.07 ± 1.60. The pretreatment MG score was 4.10 ± 0.99 and 4.23 ± 1.07 (P = 0.62) in the azithromycin and LipiFlow group, respectively. After 2 weeks, 3 months, and 6 months, the MG score was 24.20 ± 3.38, 21.67 ± 3.46, and 15.83 ± 2.41, respectively, in azithromycin group. In the LipiFlow group, the score was 13 ± 1.88, 14.27 ± 2.07, and 14.37 ± 1.85 at 2 weeks, 3 months, and 6 months, respectively, suggestive of improvement in all visits. CONCLUSION: Both oral azithromycin and LipiFlow treatment are effective in patients with MGD. The effect of LipiFlow treatment lasted longer as compared to azithromycin. The efficacy of azithromycin in resolving the symptoms of MGD was greater compared to LipiFlow in the initial 2 weeks of treatment. However, the effect deteriorated in the subsequent follow-up at 3 months and 6 months.

Purpuric Type Drug Eruption Caused by Azithromycin: A Case Report and Literature Review.

Azithromycin, an azolide antibiotic with structural and functional similarities to macrolides, possesses distinct features such as its effects persisting for seven days, an extended half-life by administering it once daily for three days, and strong antimicrobial activity. Notably, vomiting and diarrhea are recognized as the primary adverse events related to azithromycin. In this particular case, we present a unique case describing a purpuric-type drug eruption associated with azithromycin, which represents an uncommon cutaneous manifestation. A 64-year-old female developed a purpuric eruption on her trunk and lower extremities seven days after receiving daily intravenous azithromycin for upper bronchitis. A previous occurrence of punctate purpuric eruption following azithromycin administration was documented in her medical history. The diagnosis of azithromycin-induced skin eruption was confirmed based on the clinical progression and the recurrence of the eruption upon re-administration of the drug. In response to this diagnosis, the patient underwent treatment involving the discontinuation of azithromycin and the application of topical betamethasone butyrate propionate ointment. Remarkably, her eruption significantly improved within two weeks, although residual pigmentation persisted post-treatment. Additionally, we offer a comprehensive review of the literature, examining cases of drug eruptions related to azithromycin.

Comparative Study of Azithromycin Versus Doxycycline Effect on the Resistin Level in Periodontitis Patients With Type 2 Diabetes: A Randomized Controlled Clinical Trial.

AIM: The present study aimed to determine if azithromycin (AZM) and doxycycline therapy, as an adjunct to scaling and root planning (SRP), modulate host response and improve clinical outcomes in periodontitis patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: Forty-five periodontal sites in 15 periodontitis patients with T2DM received nonsurgical periodontal therapy (NSPT). In Group I, patients were placebo (not receiving any medication), Group II patients received systemic AZM therapy (AZM 250 mg/day for five days), and Group III patients received doxycycline (20 mg twice per day for three months. The resistin level was collected and measured by enzyme-linked immunosorbent assay (ELISA). Gingival index (GI), probing depth (PD), and clinical attachment level (CAL) were recorded at baseline, one-month, and three-month intervals. RESULTS: All groups showed improvement in clinical parameters and resistin levels throughout the study. The mean resistin level at three months was the highest in Group I and the lowest in Group III. Patients in Group II showed a larger decrease in mean PD than those in Group I and III. Group III had the highest gain in mean CAL, with an increase of 1.78 mm in attachment. CONCLUSION: Resistin might be a useful indicator of current disease status. In addition, benefits from adjunctive systemic use of AZM and doxycycline have been administered with non-surgical periodontal therapy.

Treatment of Mycoplasma genitalium infection in pregnancy: A systematic review of international guidelines.

BACKGROUND: Mycoplasma genitalium is an emerging pathogen, which has been linked to cervicitis, urethritis and pelvic inflammatory disease (PID). With the advent of multiplex polymerase chain reaction (PCR) panels for sexually transmitted infections, it is increasingly being identified in pregnant women. OBJECTIVES: The aim was to review international guidelines, which had explicit recommendations for treatment of M. genitalium infection in pregnancy and breastfeeding. SEARCH STRATEGY: PubMed, EMBASE and Cochrane databases were reviewed with no age, species, language or date restrictions. SELECTION CRITERIA: Studies were included if they had an explicit recommendation for treatment of M. genitalium in pregnancy. Studies were excluded if there was no recommendation in pregnancy, if they referred to other international guideline recommendations or were historical versions of guidelines. DATA COLLECTION AND ANALYSIS: References were manually reviewed and 50 papers were selected for review. Only four guidelines were included in the final analysis and they were from Europe, UK, Australia and Aotearoa New Zealand. MAIN RESULTS: All studies recommended azithromycin as first-line treatment, and advised against moxifloxacin use. The dosing schedule of azithromycin, varied between guidelines, as did the utility/safety of pristinamycin for macrolide resistant infections. Safety data was generally reassuring for azithromycin but inconsistent for pristinamycin. CONCLUSIONS: Azithromycin is the first-line treatment for macrolide susceptible or unknown resistance infections, but there is a lack of consistency regarding dosing of azithromycin or the utility/safety of pristinamycin for macrolide resistant infections in pregnancy/lactation.

Upregulation of outer membrane porin gene ompC contributed to enhancement of azithromycin susceptibility in multidrug-resistant Escherichia coli.

The outer membrane (OM) in gram-negative bacteria contains proteins that regulate the passive or active uptake of small molecules for growth and cell function, as well as mediate the emergence of antibiotic resistance. This study aims to explore the potential mechanisms for restoring bacteria to azithromycin susceptibility based on transcriptome analysis of bacterial membrane-related genes. Transcriptome sequencing was performed by treating multidrug-resistant Escherichia coli T28R with azithromycin or in combination with colistin and confirmed by reverse transcription-quantitative PCR (RT-qPCR). Azithromycin enzyme-linked immunosorbent assay (ELISA) test, ompC gene overexpression, and molecular docking were utilized to conduct the confirmatory research of the potential mechanisms. We found that colistin combined with azithromycin led to 48 differentially expressed genes, compared to azithromycin alone, such as downregulation of tolA, eptB, lpxP, and opgE and upregulation of ompC gene. Interestingly, the addition of colistin to azithromycin differentially downregulated the mph(A) gene mediating azithromycin resistance, facilitating the intracellular accumulation of azithromycin. Also, overexpression of the ompC elevated azithromycin susceptibility, and colistin contributed to further suppression of the Mph(A) activity in the presence of azithromycin. These findings suggested that colistin firstly enhanced the permeability of bacterial OM, causing intracellular drug accumulation, and then had a repressive effect on the Mph(A) activity along with azithromycin. Our study provides a novel perspective that the improvement of azithromycin susceptibility is related not only to the downregulation of the mph(A) gene and conformational remodeling of the Mph(A) protein but also the upregulation of the membrane porin gene ompC.IMPORTANCEUsually, active efflux via efflux pumps is an important mechanism of antimicrobial resistance, such as the AcrAB-TolC complex and MdtEF. Also, bacterial porins exhibited a substantial fraction of the total number of outer membrane proteins in Enterobacteriaceae, which are involved in mediating the development of the resistance. We found that the upregulation or overexpression of the ompC gene contributed to the enhancement of resistant bacteria to azithromycin susceptibility, probably due to the augment of drug uptakes caused and the opportunity of Mph(A) function suppressed by azithromycin with colistin. Under the combination of colistin and azithromycin treatment, OmpC exhibited an increased selectivity for cationic molecules and played a key role in the restoral of the antibiotic susceptibility. Investigations on the regulation of porin expression that mediated drug resistance would be important in clinical isolates treated with antibiotics.

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.

Azithromycin Induced Asthma Remission in Adults With Persistent Uncontrolled Asthma: A Secondary Analysis of a Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Asthma remission is a potential treatment goal. RESEARCH QUESTION: Does adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared with placebo? STUDY DESIGN AND METHODS: This secondary analysis used data from the AMAZES clinical trial-a double-blind placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations. The primary remission definition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids during the previous 6 months evaluated at 12 months and a 5-item Asthma Control Questionnaire score ≤ 1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (postbronchodilator FEV1 ≥ 80% or postbronchodilator FEV1 ≤ 5% decline from baseline) and complete remission (sputum eosinophil count < 3% plus the aforementioned criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. The predictors of clinical remission were identified. RESULTS: A total of 335 participants (41.5% male; median age, 61.01 years; quartile 1-3, 51.03-68.73) who completed the 12-month treatment period were included in the analysis. Twelve months of treatment with azithromycin induced asthma remission in a subgroup of patients, and a significantly higher proportion in the azithromycin arm achieved both clinical remission (50.6% vs 38.9%; P = .032) and clinical remission plus lung function criteria (50.8% vs 37.1%; P = .029) compared with placebo, respectively. In addition, a higher proportion of the azithromycin group achieved complete remission (23% vs 13.7%; P = .058). Sensitivity analyses supported these findings. Baseline factors (eg, better asthma-related quality of life, absence of oral corticosteroid burst in the previous year) predicted the odds of achieving clinical remission. Azithromycin induced remission in both eosinophilic and noneosinophilic asthma. INTERPRETATION: Adults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment may be an achievable treatment target in moderate/severe asthma, and future studies should consider remission as an outcome measure.

Injectable Hydrogel To Deliver Bone Mesenchymal Stem Cells Preloaded with Azithromycin To Promote Spinal Cord Repair.

Spinal cord injury is a disease that causes severe damage to the central nervous system. Currently, there is no cure for spinal cord injury. Azithromycin is commonly used as an antibiotic, but it can also exert anti-inflammatory effects by down-regulating M1-type macrophage genes and up-regulating M2-type macrophage genes, which may make it effective for treating spinal cord injury. Bone mesenchymal stem cells possess tissue regenerative capabilities that may help promote the repair of the injured spinal cord. In this study, our objective was to explore the potential of promoting repair in the injured spinal cord by delivering bone mesenchymal stem cells that had internalized nanoparticles preloaded with azithromycin. To achieve this objective, we formulated azithromycin into nanoparticles along with a trans-activating transcriptional activator, which should enhance nanoparticle uptake by bone mesenchymal stem cells. These stem cells were then incorporated into an injectable hydrogel. The therapeutic effects of this formulation were analyzed in vitro using a mouse microglial cell line and a human neuroblastoma cell line, as well as in vivo using a rat model of spinal cord injury. The results showed that the formulation exhibited anti-inflammatory and neuroprotective effects in vitro as well as therapeutic effects in vivo. These results highlight the potential of a hydrogel containing bone mesenchymal stem cells preloaded with azithromycin and trans-activating transcriptional activator to mitigate spinal cord injury and promote tissue repair.