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Once-daily, 3-day azithromycin versus a three-times-daily, 10-day course of co-amoxiclav in the treatment of adults with lower respiratory tract infections: results of a randomized, double-blind comparative study.

A 3-day regimen of azithromycin (500 mg once daily) and a 10-day regimen of co-amoxiclav (625 mg three times daily) were compared in a double-blind study of 67 patients with acute infectious exacerbations of chronic bronchitis (AIECBs, n = 54), acute bronchitis (n = 7), or pneumonia (n = 6). In patients treated with azithromycin, satisfactory clinical responses (cure or improvement) were seen in 24/28 (86%) patients with AIECBs, 2/4 (50%) with acute bronchitis and 2/2 (100%) with pneumonia. Responses were satisfactory in 24/26 (92%), 4/4 (100%) and 4/4 (100%) patients, respectively, receiving co-amoxiclav. Streptococcus pneumoniae and Haemophilus influenzae were the commonest pathogens isolated at baseline. At the end of treatment, baseline pathogens were eradicated in 9/10 microbiologically-assessable patients treated with azithromycin and in 10/10 treated with co-amoxiclav. Adverse events related or possibly related to treatment occurred in five patients in each treatment group; the majority of these events affected the gastrointestinal system. One patient in each treatment group discontinued therapy because of adverse events. The study, therefore, demonstrates that 500 mg azithromycin administered once daily for 3 days is as efficacious and well tolerated as co-amoxiclav given three times daily for 10 days in the domiciliary treatment of adults with acute lower respiratory tract infections.

Adolescent↗

Delivery of azithromycin to Chlamydia trachomatis-infected polarized human endometrial epithelial cells by polymorphonuclear leucocytes.

An in-vitro model was designed to evaluate whether polymorphonuclear leucocytes (PMN) loaded with azithromycin could migrate and deliver the antibiotic in a bioactive form to chlamydia inclusions in polarized human endometrial epithelial (HEC-1B) cells infected with Chlamydia trachomatis. PMN chemotaxis through the extracellular matrix and between infected epithelial cells was readily observed if the HEC-1B cells had been infected with chlamydiae for 36 or 48 h. Inclusions in infected epithelial cells exposed to PMN loaded with azithromycin were initially distinguished by deformed reticulate bodies and an excessive amount of chlamydial outer membrane vesicles. As the amount of PMN-delivered antibiotic increased, chlamydial inclusions were filled with large cell envelope 'ghosts' which were the remnants of lysed reticulate bodies. The lethal effect of azithromycin was confirmed by a reduction in the viability of infectious progeny. Our results demonstrate that the damage to chlamydiae was due to transport and delivery of azithromycin by PMN to infected genital epithelial cells. When infected HEC-1B cells were exposed to PMN not loaded with the antibiotic, chlamydial morphology was not obviously affected yet few viable progeny could be recovered. In this case, PMN-induced damage to host epithelial cells probably interrupted chlamydial nutrient acquisition and subsequent maturation and formation of infectious progeny.

Anti-Bacterial Agents↗

The combination of amphotericin B and azithromycin as a potential new therapeutic approach to fusariosis.

We investigated the interaction between amphotericin B and azithromycin in vitro against 26 clinical isolates of Fusarium. Synergy was demonstrated in all isolates. Amphotericin B MICs were reduced from a mean of 1 mg/L when tested alone to a mean of 0.37 mg/L when tested in combination with azithromycin. Azithromycin demonstrated no activity against Fusarium when tested alone (MIC > 128 mg/L). When combined with amphotericin B the mean MIC was reduced to 5.5 mg/L, a level readily achieved in tissue. Given the resistance of Fusarium to conventional therapy, the in-vitro synergy between amphotericin B and azithromycin might prove to be important in therapy for fusariosis.

Amphotericin B↗

Lysosomal alterations induced in cultured rat fibroblasts by long-term exposure to low concentrations of azithromycin.

Computer-aided simulations suggest that the doses and schedules of administration of azithromycin proposed in treatment and prophylaxis of Mycobacterium avium complex (MAC) in AIDS patients will result in drug concentrations in serum and extracellular fluids remaining for sustained periods of time in the 0.03-0.1 mg/L range. We exposed cultured rat embryo fibroblasts to these concentrations (and multiples up to 20 mg/L) for up to 16 days. Electron microscopy showed that after 7 days' incubation in 0.03 mg/L azithromycin, there was conspicuous accumulation of osmiophilic, lamellar structures (myeloid bodies) in lysosomes, suggesting the onset of a phospholipidosis. Assay of total cell phospholipids and cholesterol showed significant increases in cells exposed to > or = 1 to 5 mg/L of azithromycin in association with hyperactivity of the lysosomal enzyme cathepsin B. The data suggest that azithromycin, at extracellular concentrations pertinent to its use for MAC treatment, and perhaps also prophylaxis, causes limited morphological alterations of the lysosomes in cultured cells which are of the same nature as those developing rapidly and extensively at higher concentrations.

Animals↗

Cost-effectiveness of azithromycin for preventing Mycobacterium avium complex infection in HIV-positive patients in the era of highly active antiretroviral therapy. The Swiss HIV Cohort Study.

We conducted a cost-effectiveness analysis to determine the clinical and economic consequences of Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients in the era of highly active antiretroviral therapy (HAART) in a health care system with access unrestricted by financial barriers. The analysis was performed from a health care perspective and compared azithromycin (1200 mg/week) with no prophylaxis over a period of 10 years based on data from the Swiss HIV Cohort Study (SHCS) and randomized controlled trials. The main outcome measures were: expected survival; average health care costs; and cost-effectiveness in 1997 Swiss francs ( pound1 corresponds to about 2.3 CHF) per life-year saved. In patients with an initial CD4 count <50 cells/mm(3) and no AIDS, azithromycin increased expected survival by 4 months. In patients with AIDS, HAART durability had a major impact on expected survival and costs. Incremental survival increased from 2 to 4 months if we assumed a 10 year, instead of a 3 year, HAART effect. The cost-effectiveness of azithromycin relative to no prophylaxis in patients without AIDS was between 47,000 CHF (3-year HAART effect) and 60,000 CHF (10-year HAART effect) per life-year saved. The cost-effectiveness ratio increased to 118,000 CHF per life-year saved in patients with symptomatic AIDS. In conclusion, in the era of HAART, MAC prophylaxis with azithromycin increases expected survival and reduces health care costs substantially. Starting MAC prophylaxis in patients without AIDS is more effective and cost-effective than in patients with AIDS.

AIDS-Related Opportunistic Infections↗

Serum and WBC pharmacokinetics of 1500 mg of azithromycin when given either as a single dose or over a 3 day period in healthy volunteers.

Owing to azithromycin's prolonged half-life, shorter and shorter dosage regimens are being studied for treatment of respiratory tract infections. Previous studies have concluded that the 3 and 5 day (1.5 g total) regimens not only provide at least equal serum and WBC exposures but also equal efficacy rates. An earlier clinical study using the entire 1.5 g dose at once or the current 3 day regimen in patients with atypical pneumonia noted equal efficacy. Similar trials are currently underway in both adult and paediatric populations. The goal of the present study was to investigate whether there were equal serum and WBC exposures when azithromycin was dosed as the current 3 day regimen or as a single large dose. Equal exposures would help validate future clinical trials of single dose regimens. Twelve healthy volunteers received both azithromycin regimens (1.5 g single dose and 500 mg/day for 3 days) in random order. Serum and WBC samples were collected at baseline and repeatedly for 10 days following the first dose of each regimen. Serum samples were assayed via HPLC (CV% < 10) and WBC samples via liquid chromatography/mass spectrometry (CV% < 10). Data were modelled using noncompartmental methods. Statistics were via ANOVA with significance defined as P < 0.05. All subjects completed both regimens with minimal incidence of adverse effects. Serum data [mean (range)] demonstrated no significant difference in exposure between the two regimens [single 13.1 (3.02-20.6) mg x h/L versus 3 day 11.2 (2.98-24.5) mg x h/L: P = 0.12], although it favoured the shorter regimen. WBC results demonstrated much higher exposures than seen with serum, but no significant difference between the two regimens was identified. These results suggest that a single oral 1.5 g regimen of azithromycin for respiratory tract infections should provide exposure at least equal to currently approved treatment regimens.

Adult↗

Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for upper respiratory tract infections.

We carried out a meta-analysis of randomized controlled trials comparing 3-5 days of azithromycin with other antibiotics that are typically given in longer courses for the treatment of upper respiratory tract infections. For acute otitis media (19 comparisons including 3421 patients), acute sinusitis (11 comparisons including 1742 patients) and acute pharyngitis (16 comparisons including 2447 patients), azithromycin had similar clinical failure rates to the other antibiotics [random effects odds ratios 1.12, 95% confidence interval (CI) 0.81-1.54; 0.91, 95% CI 0.60-1.39; and 1.07, 95% CI 0.59-1.94, respectively]. The difference in clinical failures was <0.5%, and no 95% CIs exceeded 2.0%. There was no heterogeneity between studies. Subtle differences between comparators could have been due to chance. There were no significant differences in bacteriological outcomes. Azithromycin was discontinued because of adverse events in only 37 of 4870 (0.8%) patients. Short courses of azithromycin are as effective as longer courses of other antibiotics for upper respiratory tract infections. Convenience of dosing should be balanced against the increased cost of this regimen for the treatment of these common infections, where often no antibiotic may be indicated at all.

Acute Disease↗

Endothelial cell compatibility of azithromycin and erythromycin.

Phlebitis is a severe local adverse event related to the use of parenteral macrolides. In order to evaluate the effect of azithromycin and erythromycin on human venous endothelial cells, we set up an in vitro model. The intracellular levels of purine nucleotides, as adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP) and guanosine 5'-triphosphate (GTP), were measured by means of high-performance liquid chromatography. Incubation of cells with 2 mg/mL azithromycin and erythromycin resulted in a rapid decline of intracellular ATP from 12.5 +/- 0.9 nmol/million cells to 4.1 +/- 0.3 and 2.6 +/- 0.4 nmol/million cells, respectively, after 60 min. In addition, ADP was extensively depleted from 2.1 +/- 0.17 nmol/million cells to 0.8 +/- 0.09 and 0.8 +/- 0.13 nmol/million cells after 60 min. After exposure of 0.5 mg/mL azithromycin and erythromycin, no significant decline of intracellular high-energy phosphate levels occurred after 20 and 60 min. Based on these results, solutions of azithromycin and erythromycin may not be well tolerated and may cause local adverse reactions even if diluted according to the manufacturer's recommendation.

Anti-Bacterial Agents↗

Impact of carbon dioxide on the susceptibility of key respiratory tract pathogens to telithromycin and azithromycin.

OBJECTIVES: To determine the quantitative differences in telithromycin and azithromycin MIC values against Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes obtained using two recommended and commonly used methodologies: CLSI reference standard broth microdilution in ambient air and Etest((R)) concentration gradient in CO(2). METHODS: Four hundred clinical isolates (S. pneumoniae, n = 200; H. influenzae, n = 100; S. pyogenes, n = 100) were evaluated in seven independent laboratories. Telithromycin and azithromycin MICs were determined using CLSI broth microdilution panels incubated in ambient air and Etest strips incubated in CO(2). Standard quality control reference strains-S. pneumoniae ATCC 49619 (n = 10) and H. influenzae ATCC 49247 (n = 10)-were also tested. RESULTS: Telithromycin and azithromycin Etest MICs in CO(2) were elevated for all organisms when compared with values obtained using broth microdilution in ambient air. Telithromycin geometric mean MIC values increased in CO(2) by 2.05, 1.00 and 1.78 log(2) dilutions for S. pneumoniae, H. influenzae and S. pyogenes, respectively. The corresponding values for azithromycin were 2.54, 1.21 and 3.0 log(2) dilutions, respectively. CONCLUSIONS: Telithromycin MICs measured using Etest in CO(2) are consistently elevated compared with those generated by CLSI broth microdilution measured in ambient air. These findings indicate that Etest should not be routinely used for the determination of telithromycin MICs against S. pneumoniae, H. influenzae and S. pyogenes, unless appropriate corrective factors are applied before reporting MICs or applying interpretive susceptibilities. Based on results from this study, Etest MIC breakpoints and quality control ranges are proposed.

Anti-Bacterial Agents↗

Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS.

OBJECTIVE: To assess the safety, tolerance and activity of increasing doses of azithromycin in combination with pyrimethamine for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS. DESIGN: A phase I/II dose-escalation study of oral azithromycin in combination with pyrimethamine. SETTING: Eight clinical sites in the United States. PATIENTS: Forty-two adult HIV-infected patients with confirmed or presumed acute TE. METHODS: Patients were enrolled into three successive cohorts receiving azithromycin 900, 1200 and 1500 mg a day with pyrimethamine as induction therapy. The induction period was 6 weeks followed by 24 weeks of maintenance therapy. MAIN OUTCOME MEASURES: Patient response was evaluated clinically and radiologically. RESULTS: Of the 30 evaluable patients, 20 (67%) responded to therapy during the induction period. Ten experienced disease progression. Of the 15 patients who received maintenance therapy, seven (47%) relapsed. Six patients discontinued treatment during the induction period as a result of reversible toxicities. Treatment-terminating adverse events occurred most frequently among the patients receiving the 1500 mg dose. CONCLUSION: The combination of azithromycin (900-1200 mg a day) and pyrimethamine may be useful as an alternative therapy for TE among patients intolerant of sulfonamides and clindamycin, but maintenance therapy with this combination was associated with a high relapse rate. The combination was safe, but low-grade adverse events were common.

AIDS-Related Opportunistic Infections↗

Azithromycin compared with rifampin for eradication of nasopharyngeal colonization by Neisseria meningitidis.

OBJECTIVES: To evaluate the efficacy and safety of azithromycin compared with rifampin for eradication of nasopharyngeal carriage of Neisseria meningitidis METHODS: Pharyngeal swabs were obtained from 500 students attending nursing school in Cairo, Egypt, to determine the colonization rate with N. meningitidis. Colonized individuals were randomized to receive azithromycin (500 mg once) or rifampin (600 mg twice daily for four doses). Subjects were then recultured 1 and 2 weeks posttreatment to determine the effectiveness of the antibiotic therapy for eradication of meningococcal nasopharyngeal colonization. RESULTS: Individuals treated with azithromycin had a 93% eradication rate at 1 and 2 weeks posttreatment comparable with 95 and 91%, respectively, for rifampin. No significant side effects were reported by any subjects treated with either antibiotic. CONCLUSION: Azithromycin is effective in the eradication of N. meningitidis from the nasopharynx of asymptomatic colonized individuals and deserves further evaluation for use as prophylaxis against N. meningitidis.

Adolescent↗

Single dose azithromycin for the treatment of chancroid: a randomized comparison with erythromycin.

BACKGROUND AND OBJECTIVES: Chancroid is endemic in sub-Saharan Africa and enhances the sexual transmission of the human immunodeficiency virus Type 1 (HIV-1). Azithromycin is an orally absorbed macrolide antibiotic that is active against Haemophilus ducreyi, the causative agent of chancroid, and has pharmacokinetic properties that are suitable for single dosing. STUDY DESIGN: In a randomized single-blinded study of 127 men presenting to a referral STD clinic with culture proven chancroid, we compared the efficacy of azithromycin, administered as a single 1 g dose, with erythromycin 500 mg given 4 times daily for 7 days. RESULTS: Cure rates were 89% (73 of 82) in the azithromycin group and 91% (41 of 45) in the erythromycin group. A failure to respond to treatment was associated with HIV-1 seropositivity and a lack of circumcision. Both regimens were well tolerated. CONCLUSIONS: Azithromycin, given as a single 1 g oral dose, is an effective treatment for chancroid in men, and offers major prescribing advantages over erythromycin.

AIDS-Related Opportunistic Infections↗

Quantitative determination of the antibiotic azithromycin in human serum by high-performance liquid chromatography (HPLC)-atmospheric pressure chemical ionization mass spectrometry: correlation with a standard HPLC-electrochemical method.

A specific assay for the quantitative determination of the new antibiotic azithromycin in a low volume of human serum is described. The assay uses on-line high-performance liquid chromatography (HPLC) and atmospheric pressure chemical ionization mass spectrometry (HPLC-APCI). Deuterium-labeled azithromycin was synthesized and used as the internal standard of the assay. The drug and the internal standard are extracted from 50 microliters of serum, and aliquots are injected onto a standard reverse-phase HPLC column. The effluent from the HPLC column at 1 ml/min is introduced into the atmospheric pressure source of a SCIEX API III mass spectrometer. Azithromycin concentrations in serum are determined by the selected monitoring of the protonated molecular ions of the drug and the internal standard. Our assay yields accurate and precise results over the range 10 ng/ml to 250 ng/ml. The correlation between the assay and a standard HPLC-electrochemical method, requiring a larger volume of serum, has been determined. The two methods showed excellent agreement. Because of its low volume requirement, our HPLC-APCI assay can be substituted for the standard assay for the investigation of azithromycin pharmacokinetics in children.

Azithromycin↗

Three-day antibiotic therapy with azithromycin and tinidazole plus lansoprazole or pantoprazole to cure Helicobacter pylori infection: a pilot study.

OBJECTIVE: The aim of the present study was to investigate and compare the effects of two proton-pump inhibitors, lansoprazole (Limpidex 30 mg, Sigmatau) vs pantoprazole (Peptazol 40 mg, Boehringer Mannheim), included in a three-day antibiotic therapy regimen with azithromycin (Zitromax 500 mg, Pfizer) and tinidazole (Fasigin 500 mg, Pfizer). DESIGN: Seventy consecutive, H. pylori-positive patients were randomly pre-treated with lansoprazole 30 mg o.d. (once daily) or pantoprazole 40 mg o.d. for two days, and subsequently respectively assigned to one of the two following treatment regimens, given for only three days: regimen A (LAT) comprising lansoprazole 30 mg o.d. plus azithromycin 500 mg o.d. and tinidazole 500 mg b.i.d. (bis in die), or regimen B (PAT) comprising pantoprazole 40 mg o.d. plus azithromycin 500 mg o.d. and tinidazole 500 mg b.i.d. H. pylori status was evaluated by means of histology and rapid urease test at entry, and by 13C-urea breath test alone 8 weeks after treatment. MAIN OUTCOME MEASURES: Sixty-nine of the enrolled patients completed the study: 34 in the LAT group and 35 in the PAT group. One patient in the LAT group was lost to follow-up. In the LAT group, after the end of treatment, 28/34 patients were H. pylori-negative (per protocol: 82%; intention-to-treat: 80%). In the PAT group, after treatment, 29/35 patients were H. pylori-negative (per protocol and intention-to-treat: 83%). Mild or slight side-effects occurred in only one patient in the LAT group and in one in the PAT group. CONCLUSIONS: From this study there is no evidence that either of the two proton-pump inhibitors used is preferable in a three-day antibiotic regimen with azithromycin and tinidazole. The excellent side-effect and tolerability profiles, associated with acceptable eradication rates, make the two treatment regimens we tested particularly useful when patient compliance is difficult to achieve.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Role of atypical bacteria and azithromycin therapy for children with recurrent respiratory tract infections.

BACKGROUND: The aim of this study of 352 patients, 1-14 years of age, with acute respiratory infections and a history of recurrent respiratory tract infections (RRTIs), and 208 healthy subjects was to evaluate whether Mycoplasma pneumoniae and Chlamydia pneumoniae played a role in causing acute respiratory episodes among children with RRTIs and whether specific antibiotic treatment for these bacteria could improve the acute episodes and reduce recurrences. METHODS: The patients were blindly randomized to receive azithromycin (10 mg/kg/d for 3 days weekly, for 3 weeks) together with symptom-specific agents or symptom-specific agents alone. Acute M. pneumoniae and/or C. pneumoniae infection was diagnosed if the child had a significant antibody response in paired sera and/or if the DNA of the bacteria was detected in nasopharyngeal aspirates. RESULTS: Atypical bacterial infections were identified for 190 patients (54.0%) and 8 healthy control subjects (3.8%; P < 0.0001). Short term (1-month) clinical success was significantly more frequent among the patients who had received azithromycin together with symptom-specific agents than among those who had received symptom-specific agents alone, but the difference was significant only for the group of patients with atypical bacteria. In contrast, long term (6-month) clinical success was significantly more frequent among the patients who had received azithromycin in addition to symptom-specific agents, regardless of whether they experienced infections with atypical bacteria or other pathogens, although positive outcomes were significantly more frequent among those with atypical bacteria. CONCLUSIONS: Atypical bacteria seem to play a role among children with RRTIs, and prolonged azithromycin therapy can significantly improve the acute episodes and reduce the risk of recurrences.

Adolescent↗

Antimicrobial-resistant Shigella sonnei: limited antimicrobial treatment options for children and challenges of interpreting in vitro azithromycin susceptibility.

BACKGROUND: Antimicrobial-resistant Shigella sonnei is a growing problem in the United States and poses treatment challenges particularly among children. Azithromycin is recommended as an alternative oral agent for shigellosis. METHODS: All isolates of Shigella submitted to Johns Hopkins clinical laboratory during the outbreak year (2002) were compared with a historical comparison group (1996-2000). Isolates were considered multiresistant if they were resistant to ampicillin and trimethoprim-sulfamethoxazole (TS). Selected outbreak and reference isolates were tested for azithromycin susceptibility by E-test, disk diffusion and broth dilution methods. RESULTS: Between 1996-2000, among the 111 isolates submitted, 63% were from pediatric patients; 63% of isolates were resistant to ampicillin and 12% to TS. In 2002, among the 205 isolates submitted, 82% were from pediatric patients; 91% isolates were resistant to ampicillin and 67% to TS. The proportion of multiresistant isolates increased from 6% in 1996 to 65% in 2002 (P < 0.05). Azithromycin susceptibility by E-test and disk diffusion demonstrated 2 zones of inhibition for S. sonnei. Interpretation using the inner zone resulted in higher MICs (minimal inhibitory concentration) compared with the outer zones by E-test (P < 0.0001) and disk diffusion (P < 0.0001). CONCLUSIONS: With increasing interest in using azithromycin for shigellosis, clinical laboratories should be aware of the interpretation difficulty caused by the dual-zone phenomenon seen with E-test and disk diffusion methods for S. sonnei.

Adolescent↗

Post-antibiotic effect of azithromycin and erythromycin on streptococcal susceptibility to phagocytosis.

The effect of azithromycin and erythromycin on growth, cell surface hydrophobicity and the susceptibility to the bactericidal activity of human polymorphonuclear leucocytes (PMNL) was examined in four Streptococcus species. Exposure to either 10 x MIC azithromycin or erythromycin induced a post-antibiotic effect (PAE) of between 2.4 and 4.3 h. Erythromycin caused a longer PAE for S. sanguis than azithromycin under the same conditions. The cell surface charge (hydrophobic or hydrophilic) of the streptococci was altered significantly during PAE; loss of hydrophobicity was induced by both macrolides, and this effect was variable amongst the species. The decrease in hydrophobicity was not related to inhibition of growth. The effect of each drug during PAE on the interaction of opsonised suspensions of the streptococci with human PMNL revealed that erythromycin, and to a lesser extent azithromycin, increased susceptibility to the bactericidal activity of human PMNL; this effect was abolished following PAE. The present study clearly showed that PAE should not only be considered as delayed bacterial growth, but also as modulation of bacterial susceptibility to phagocytosis which may influence the outcome of the host-parasite relationship.

Azithromycin↗

Susceptibility of Streptococcus pyogenes to azithromycin, clarithromycin, erythromycin and roxithromycin in vitro.

The susceptibility of 180 clinical isolates of Streptococcus pyrogenes from six regions of The Netherlands to the macrolide antibiotics azithromycin, clarithromycin, erythromycin and roxithromycin was analysed. The results of a microbroth MIC method, the E-test method and a disk diffusion assay were compared, and the MBC determined. In addition, the susceptibility to erythromycin of 436 clinical isolates of S. pyogenes from the Leiden region was determined. The microbroth MIC90s of azithromycin, clarithromycin, erythromycin and roxithromycin for group A streptococci were < or = 0.5 mg/L. Erythromycin had the lowest MIC90 (0.09 mg/L). The MIC data obtained with the E-test method suggested that clarithromycin and erythromycin had slightly higher anti-streptococcal activity than azithromycin and roxithromycin in vitro. MICs obtained with the E-test were lower than those found with the microbroth method. Only minor discrepancies were observed among the three methods. The MBC50 for both clarithromycin and erythromycin was 0.75 mg/L and 5.0 mg/L for azithromycin and roxithromycin. None of the 180 strains and two of the collection of 436 strains (0.5%) were resistant to erythromycin and the other macrolides tested; MICs ranged from 1 to 16 mg/L. The erythromycin-resistant strains showed an inducible type of macrolide-lincosamide-streptogramin B (MLS) resistance.

Anti-Bacterial Agents↗