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PubMed2003

Azithromycin therapy in patients with chronic Chlamydia pneumoniae infection and coronary heart disease: immediate and long-term effects on inflammation, coagulation, and lipid status in a double-blind, placebo-controlled study.

Background: An association between Chlamydia pneumoniae (Cp) infection and coronary heart disease (CHD) has already been reported. We investigated the relationship between Cp infection and other risk factors in CHD patients, as well as the effects of azithromycin treatment. Methods: We studied 38 patients with Cp infection (Cp-pos) and 15 without (Cp-neg). Cp-pos patients had, both at inclusion and 2 years prior to inclusion, elevated Cp-specific IgA-antibodies, with or without the presence of pharyngeal Cp by polymerase chain reaction (PCR) detection. Blood was analyzed for Cp-antibodies, interleukin-6, interleukin-1 receptor antagonist (IL-1ra), CRP, orosomucoid, fibrinogen, leukocytes, PAI-1, tPA, von Willebrand factor (vWf), platelet count and aggregation, and lipids. Cp-pos patients were randomized to placebo or oral azithromycin, 500 mg on day 1 and then 250 mg/day for 4 days, with repeated therapy after 3 weeks. Blood was taken immediately, as well as 3 months and 2 years after therapy. Results: CRP and IL-1ra levels were higher in Cp-pos than in Cp-neg patients: median, interquartile range 8.5 (3.0-20) vs. 2.0 (1.0-3.8) mg/l, and 316 (165-404) vs. 178 (118-195) ng/l, p=0.0006 and p=0.002, and platelet aggregation was lower: 4.8 (2.9-6.4) vs. 8.1 (4.7-11.4) Omega, p<0.05. tPA levels increased in azithromycin-treated patients between entry and 3-month follow-up: mean+/-S.D. 3.7+/-4.2 vs. 1.0+/-2.1 microg/l, p<0.05. Other variables did not differ. Conclusions: Cp infection was associated with increased inflammatory activity and lower platelet aggregability, suggesting that inflammation may be of greater pathophysiological importance than platelet activity in these patients. Although an effect on Cp infection was not shown, azithromycin may have a positive effect on fibrinolysis, as increased levels of tPA were observed in the treatment group.

Journal Article↗

PubMed2026

Heterogeneity of azithromycin resistance markers in Neisseria gonorrhoeae and challenges in implementing molecular assays for routine surveillance.

Neisseria gonorrhoeae is the second most prevalent bacterial sexually transmitted infection and a major contributor to the global antimicrobial resistance crisis. The World Health Organization (WHO) has designated N. gonorrhoeae as a high-priority pathogen due to its resistance to nearly all empirically recommended therapies. While dual therapy with ceftriaxone and azithromycin initially demonstrated efficacy, the rapid global rise in azithromycin resistance over the past five years threatens the efficacy of this regimen. Resistance mechanisms, including mutations in the 23S rRNA gene and overexpression of the MtrCDE efflux pump, are highly heterogeneous, complicating molecular diagnostic efforts. This review examines the evolving landscape of azithromycin resistance, highlighting key mechanisms of resistance, and recent epidemiological and genomic surveillance data. We discuss challenges in implementing molecular assays for routine resistance monitoring due to molecular heterogeneity in azithromycin resistance markers and emphasize the critical need for tailored approaches based on local genetic epidemiology. Enhanced surveillance and molecular diagnostics are essential to sustaining effective treatment strategies and combating gonococcal resistance.

Antimicrobial resistance↗

PubMed2026

Azithromycin-resistant Salmonella enterica Typhi with AcrB R717L/Q mutations in the United States.

BACKGROUND AND OBJECTIVES: Azithromycin is a critical oral treatment for typhoid fever caused by Salmonella enterica serovar Typhi (Salmonella Typhi), since XDR has rendered other first-line treatment options ineffective. Azithromycin resistance conferred by amino acid changes in AcrB, an AcrAB-TolC efflux pump component, represents an emerging public health concern. Leveraging phenotypic and genotypic data from U.S. Salmonella Typhi surveillance systems, this study describes the prevalence, phenotype and genomic epidemiology of Salmonella Typhi with AcrB mutations in U.S. patients since the first detection in 2015. METHODS: AST and WGS data of >3000 Salmonella Typhi isolates were used to identify all cases with an AcrB mutation in the United States (2015-2025). We calculated annual prevalence and MIC ranges. Phylogenetic analysis was used to contextualize U.S. cases of Salmonella Typhi with an AcrB mutation within all globally reported cases. RESULTS: While the prevalence of AcrB mutations in the United States is low (1.5%), it has risen significantly in recent years, from 0.2% in 2016-2022 to 2.2% in 2023-2025. This increase is predominantly driven by clonal expansion of existing strains circulating in South Asia. AcrB mutations do not reliably confer resistance to azithromycin (MIC ≥ 32 mg/L), complicating clinical interpretation. CONCLUSIONS: The prevalence of AcrB mutations in Salmonella Typhi is increasing in the United States, and likely globally, given that U.S. data function as an informal proxy for regions without routine surveillance infrastructure. Clinical outcomes data are needed to inform Salmonella Typhi treatment guidelines and potentially amend clinical breakpoints for azithromycin.

Journal Article↗

PubMed1996

In-vitro interaction of azithromycin and fluoroquinolones against gram-positive and gram-negative bacteria.

OBJECTIVE: To determine the combined in-vitro effects of azithromycin plus the fluoroquinolone ofloxacin or lomefloxacin against gram-positive and gram-negative bacteria. METHODS: Fractional inhibitory (FIC) and fractional bactericidal concentration indices of azithromycin and the fluoroquinolone were determined using a microtiter-checkerboard method. Clinical isolates of Staphylococcus aureus, Streptococcus pneumoniae, Neisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas cepacia, Haemophilus influenzae, Xanthomonas maltophilia and Acinetobacter calcoaceticus were studied. Fourteen strains of S. aureus were also studied in time-kill curves with azithromycin (4 mg/L), lomefloxacin (6 mg/L) and the two in combination. RESULTS: No synergism or antagonism was found in inhibitory assays. However, bactericidal assays revealed antagonism with some strains of S. aureus, S. pneumoniae, X. maltophilia, A. calcoaceticus, P. aeruginosa, P. cepacia, K. pneumoniae and E. coli. Kill-curve results with 14 strains of S. aureus showed no antagonism with four strains of methicillin-resistant S. aureus (MRSA), and antagonism with one strain of MRSA and seven methicillin-susceptible S. aureus (MSSA). CONCLUSIONS: In-vitro exposure to combinations of azithromycin and a fluoroquinolone does not produce a synergistic effect. Antagonism was found in bactericidal assays against some gram-negative bacteria and MSSA; caution is therefore recommended in the use of macrolides and quinolones against these organisms.

Journal Article↗

PubMed2006

Azithromycin in chronic fatigue syndrome (CFS), an analysis of clinical data.

BACKGROUND: CFS is a clinical state with defined symptoms, but undefined cause. The patients may show a chronic state of immune activation and treatment with an antibiotic in this subgroup has been suggested. METHODS: In a retrospective study, the response of CFS patients to azithromycin, an antibiotic and immunomodulating drug, has been scored from the patients records and compared with clinical and laboratory data. Azithromycin was not the first choice therapy, but offered when the effect of counseling and L-carnitine was considered insufficient by the patient and the clinician. RESULTS: Of the 99 patients investigated, 58 reported a decrease in the symptoms by the use of azithromycin. These responding patients had lower levels of plasma acetylcarnitine. CONCLUSION: The efficacy of azithromycin in the responsive patients could be explained by the modulating effect on a chronic primed state of the immune cells of the brain, or the activated peripheral immune system. Their lower acetylcarnitine levels may reflect a decreased antioxidant defense and/or an increased consumption of acetylcarnitine caused by oxidative stress.

Journal Article↗

PubMed2004

Adsorptive stripping voltammetric determination of azithromycin at a glassy carbon electrode modified by electrochemical oxidation.

The adsorptive and electrochemical behaviors of azithromycin were investigated on a glassy carbon electrode that was electrochemically treated by anodic oxidation at +1.8 V, following potential cycling in the potential range from -0.8 to +1.0 V. The resulting electrode showed good activity to improve the electrochemical response of the drug. An adsorptive stripping voltammetric method for the determination of azithromycin at an electrochemically activated glassy carbon electrode has been developed. Azithromycin was accumulated in phosphate buffer, pH 6, at a potential of +0.3 V (vs. Ag/AgCl electrode) for a certain time, and then determined by differential pulse voltammetry. The oxidative peak current at +0.82 V, at a scan rate of 20 mV s(-1), was a linear function of the concentration in the ranges of 0.25 - 2 microg mL(-1) and 1 - 10 microg mL(-1) using a 240 or 60 s(-1) preconcentration time, respectively. Application of the method to the determination of azithromycin in pharmaceuticals resulted in an acceptable deviation from the stated concentration. The preconcentration medium-exchange approach was utilized for the selective determination of the drug in spiked urine samples with satisfactory results. The peak current was linear with the drug concentration in the range of 0.5 - 3.5 microg per mL urine. The detection limit was 0.2 microg mL(-1) urine. The recovery levels of the method reached 96.3%.

Journal Article↗

PubMed1988

Efficacy of a new macrolide (azithromycin). For acute otitis media in the chinchilla model.

The efficacy of an investigational macrolide, azithromycin, in the treatment of acute otitis media consequent to an infection by a strain of beta-lactamase-producing Haemophilus influenzae, was evaluated using the chinchilla animal model. The results indicate that the azithromycin high-dosage (30 mg/kg/d) group has a significantly higher rate for effusion sterilization and resolution as compared with the other treatment groups. Unique pharmacokinetic properties of this investigational antimicrobial were demonstrated. Clinical trials using azithromycin for the treatment of upper respiratory tract infections, including otitis media, are warranted.

Acute Disease↗

PubMed2003

Analysis of unknown compounds in azithromycin bulk samples with liquid chromatography coupled to ion trap mass spectrometry.

A selective reversed-phase liquid chromatography/mass spectrometry (LC/MS(n)) method is described for the identification of azithromycin impurities and related substances in commercial azithromycin samples. Mass spectral data are acquired on an LCQ ion trap mass spectrometer equipped with an atmospheric pressure chemical ionization interface operated in positive ion mode. The LCQ provides on-line LC/MS(n) capability, making it ideally suited for identification purposes. In comparison with UV detection, this hyphenated technique provides as its main advantage efficient identification of novel substances without time-consuming isolation and purification procedures. Using this technique, six novel related substances detected in commercial azithromycin samples have been studied.

Anti-Bacterial Agents↗

PubMed1988

Comparative in vitro activity of the new oral macrolide azithromycin.

The in vitro activity of the new oral macrolide azithromycin was compared with that of erythromycin against gram-positive and gram-negative aerobic and anaerobic bacteria. Ninety percent of hemolytic streptococci groups A and B, and Streptococcus pneumoniae were inhibited by 0.5 microgram/ml. Activity of azithromycin was similar to that of erythromycin; erythromycin-resistant staphylococci and streptococci were not inhibited. Azithromycin was more active than erythromycin against Haemophilus influenzae (MIC90 1 microgram/ml) and Neisseria gonorrhoeae. It inhibited Campylobacter spp. and Pasteurella multocida, and had an MIC50 of 8 micrograms/ml for Escherichia coli, Salmonella spp., Shigella spp. and Yersinia enterocolitica compared to an erythromycin value of greater than 64 micrograms/ml.

Azithromycin↗

PubMed1989

Quality control parameters and interpretive criteria for in vitro susceptibility tests with the macrolide azithromycin. Collaborative Antimicrobial Susceptibility Testing Group.

Quality control parameters for broth microdilution and disk diffusion susceptibility tests were defined and the interpretive criteria for disk diffusion tests reviewed. For interpretation of tests with 15 micrograms azithromycin disks, the following criteria are recommended: greater than or equal to 19 mm for the susceptible category (MIC less than or equal to 2.0 micrograms/ml) and less than or equal to 15 mm for the resistant category (MIC greater than or equal to 8.0 micrograms/ml). Using these criteria, there was 97% overall agreement between broth dilution and disk diffusion tests; Haemophilus influenzae isolates were susceptible to azithromycin by both methods. The quality control strain Staphylococcus aureus ATCC 25923 gave zones of 21 to 26 mm in diameter in a six-laboratory collaborative study. In azithromycin broth microdilution tests the following MIC control limits are recommended: Escherichia coli ATCC 25922, 2.0-8.0 micrograms/ml; Staphylococcus aureus ATCC 29213, 0.25-1.0 micrograms/ml; and Enterococcus faecalis ATCC 29212, 1.0-4.0 micrograms/ml.

Azithromycin↗

PubMed1990

Intraphagocytic activity of erythromycin, roxithromycin and azithromycin.

The intraphagocytic activity of erythromycin, roxithromycin and azithromycin against phagocytosed Staphylococcus aureus was compared. Erythromycin and roxithromycin both acted bacteriostatically at concentrations corresponding to 10 X MIC. Azithromycin, however, did not prevent intracellular proliferation of the staphylococci. On comparison of the pH dependency of the antibacterial activity of the three drugs, azithromycin was found to be inactivated earlier in an acidic milieu.

Azithromycin↗

PubMed1991

Concentrations of azithromycin in human tonsillar tissue.

Patients scheduled to undergo tonsillectomy were administered 500 mg oral azithromycin as two 250 mg capsules given 12 h apart. Between 9 h and one week after the second dose, tonsil samples were taken during surgery and assayed for azithromycin. Mean concentrations in tonsillar tissue, 12 and 24 h after the second of the two 250 mg doses given 12 h apart, were 4.5 and 3.9 micrograms/g, respectively. Concurrent mean serum concentrations were approximately 0.03 and 0.01 micrograms/g, respectively. The mean concentration in tonsillar tissue 7.5 days after the last dose was 0.93 micrograms/g. The apparent half-life of drug in the tissue was 76 h. The ratio of mean concentration in tissue to that in serum was greater than 150-fold for all time intervals. The presence of high azithromycin concentrations in tonsillar tissue suggests that a once-daily regimen over five days or less may be effective in treating tonsillo-pharyngitis.

Administration, Oral↗

PubMed1991

Concentration of azithromycin in human prostatic tissue.

Prostatic tissue was obtained from 36 patients at two study locations and assayed for azithromycin by HPLC or bioassay. The mean concentration of azithromycin in human prostatic tissue (2.54 micrograms/ml) 14 h after 500 mg oral dosing (two 250 mg doses 12 h apart) was much greater than plasma concentrations (less than or equal to 0.1 micrograms/ml). Azithromycin was slowly eliminated from prostatic tissue (half-life 60 h) and a mean concentration of 0.62 micrograms/ml remained 137 h after dosing.

Administration, Oral↗

PubMed1993

Azithromycin resistance in Campylobacter jejuni and Campylobacter coli.

The MICs of erythromycin, azithromycin and ciprofloxacin were determined for 60 human fecal isolates of Campylobacter. Of these, 30 strains selected on the basis of their resistance to erythromycin by disk diffusion were highly resistant to both erythromycin and azithromycin. Nine of these selected isolates were resistant to ciprofloxacin. The remaining 30 strains were non-selected, consecutive isolates of Campylobacter susceptible to erythromycin by disk diffusion and were shown to be two- to five-fold more susceptible to azithromycin than to erythromycin as determined by MIC testing.

Azithromycin↗

PubMed1999

Short-term treatment of pertussis with azithromycin in infants and young children.

A prospective, open, noncomparative study was conducted to assess the efficacy and safety of azithromycin given once daily for 3 or 5 days to eradicate Bordetella pertussis from the upper respiratory tract of infants and young children. Seventeen children received azithromycin in a dose of 10 mg/kg on day 1 followed by 5 mg/kg once daily for four consecutive days, and 20 were given 10 mg/kg once daily for 3 days. Seven days after the initiation of therapy, 33 of 35 (94.3%) patients had negative cultures for Bordetella pertussis. On day 14, cultures from all 34 evaluable patients were negative. These findings suggest that a controlled, comparative study of erythromycin versus short-term administration of azithromycin is justified.

Anti-Bacterial Agents↗

PubMed2001

Relative potency of telithromycin, azithromycin and erythromycin against recent clinical isolates of gram-positive cocci.

A ketolide (telithromycin), an azalide (azithromycin) and a macrolide (erythromycin) were tested against 2,733 isolates of gram-positive cocci gathered from 11 different medical centers. Telithromycin was active against erythromycin-resistant staphylococci that were susceptible to clindamycin but was not active against those that were resistant to clindamycin. More than 99% of all Streptococcus pneumoniae and Streptococcus pyogenes isolates were susceptible to 1 microg/ml of telithromycin including erythromycin- and azithromycin-resistant strains. Telithromycin was not only more potent than azithromycin against macrolide-susceptible strains, it was also active against most macrolide-resistant strains. Although the prevalence of macrolide-resistant pneumococci increased from 19% to 27% between 1997 and 1999, macrolide resistance among other gram-positive cocci did not change substantially in that 2-year period.

Anti-Bacterial Agents↗

PubMed2004

Longterm azithromycin therapy for three patients with chronic lower respiratory tract infections.

Longterm macrolide therapy has been reported to be effective in treating chronic lower respiratory tract infections (CLRTIs). In this context, erythromycin and clarithromycin are usually used for this purpose. However, refractory cases are occasionally encountered, thereby indicating a major problem pending. In the present study, we administered azithromycin to three patients with CLRTIs whose clinical course had been unsatisfactory with longterm therapy of either erythromycin or clarithromycin. Following longterm therapy with azithromycin, both the incidence of acute exacerbations and the sputum volume were decreased. A significant change in the sputum flora was observed, without obvious side effects; however, no improvement was evidenced in the findings on flow volume curve tests and arterial blood gas analysis. In advanced disease, longterm azithromycin therapy may be as effective as that with erythromycin or clarithromycin; in our view, however, its efficacy may be limited, and large-scale clinical trials are required to determine the most suitable macrolide for the treatment of CLRTIs.

Adult↗

PubMed2006

Azithromycin as prophylaxis for the prevention of postoperative infection in impacted mandibular third-molar surgery.

Rotational use of antimicrobials is one of the strategies that have been suggested to reduce the development of drug-resistant bacteria. Cycling of homogeneous antimicrobial exposure is, however, unlikely to control the emergence of antimicrobial resistance. Penicillins and cephalosporins have been extensively used for therapeutic and prophylactic management of oral infection. The aim of the study was to investigate the clinical effects of azithromycin as prophylaxis on the prevention of postoperative infection in impacted mandibular third-molar surgery. The study design was a retrospective, single-center review. One (2.2%) of all 45 patients exhibited dry socket infection. In several categories, there was significant effectiveness of azithromycin in comparison with other antimicrobials, although there was no significant difference in the occurrence rate of dry socket infection. Azithromycin might be of value for prophylactic use in impacted mandibular third-molar surgery in which penicillins and cephalosporins were mainly used. Therefore, it might be available for one of the rotational agents.

Adolescent↗