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Activity of buforin II alone and in combination with azithromycin and minocycline against Cryptosporidium parvum in cell culture.

The in vitro anti-cryptosporidial activity of buforin II alone and in combination with azithromycin and minocycline was investigated. Buforin II showed moderate activity, which increased with increasing concentration to 55.7% suppression of growth at 20 microM. Moreover, its activity was enhanced when it was combined with either azithromycin or minocycline with >90% parasite reduction at the highest concentration tested. Buforin II may be active in inhibiting Cryptosporidium parvum growth in vitro upon combination with either azithromycin or minocycline.

Animals↗

In vitro effects of azithromycin on Salmonella typhi: early inhibition by concentrations less than the MIC and reduction of MIC by alkaline pH and small inocula.

To explain good clinical results of azithromycin in patients with typhoid fever, 10 strains of Salmonella typhi were grown in cation-adjusted Mueller-Hinton broth. MICs of azithromycin were 4-16 mg/L. At a sub-MIC of 2 mg/L, early inhibition of growth was shown at 2, 4 and 8 h of incubation, but at 24 and 48 h growth to turbidity occurred. At 4 mg/L, inhibition occurred up to 8 h, after which growth towards turbidity followed. Elongated curved bacilli formed in broth containing 4 mg/L after 24-48 h. Adjusting the pH of the broth with phosphate-citrate buffer to 7.5 and 8.0 caused reductions in MICs to 0.25-0.5 mg/L. Large inocula of 10(6) cfu/mL resulted in median MICs four- to six-fold greater than with inocula of 10(1)-10(3) cfu/mL. An inoculum of 10 bacteria per mL in broth at pH 7.5 resulted in an MIC of 0.13 mg/L. Clinical benefits in patients may occur because of early inhibition by sub-MIC concentrations of azithromycin, and due to lower MICs at alkaline pH and lower MICs with small inocula that may correspond to the low-grade bacteraemia in typhoid fever.

Anti-Bacterial Agents↗

The effect of azithromycin and clarithromycin on ex vivo interleukin-8 (IL-8) release from whole blood and IL-8 production by human alveolar macrophages.

We investigated the effects of azithromycin and clarithromycin, two antibiotics that possess a broad spectrum of antimicrobial activity (including antimycobacterial activity), on interleukin-8 (IL-8) release from human whole blood leucocytes and lung macrophages. Ex vivo stimulation of leukocytes with either of the antibiotics (0.04-40 mg/L) significantly increased IL-8 secretion. Incubation of alveolar macrophages with different concentrations of azithromycin or clarithromycin modified IL-8 production: it increased at a drug concentration of 4 mg/L and decreased at concentration of 400 mg/L. Our findings suggest that azithromycin and clarithromycin may alter IL-8 production, thus enhancing the clinical effectiveness of these antibiotics.

Analysis of Variance↗

Effect of increased inoculum of Salmonella typhi on MIC of azithromycin and resultant growth characteristics.

This study was designed to investigate the effect of an increased inoculum on the MIC of azithromycin for Salmonella typhi. Growth curves of nine strains were obtained in cation-adjusted Mueller-Hinton broth containing azithromycin at concentrations of 0-32 mg/L, and comparisons made between inoculation with large inocula, estimated as 10(7) cfu/mL, and with small inocula of c. 10(3) cfu/mL. Turbidity developed only with large inocula after 4-8 h in the presence of 8 or 16 mg/L of azithromycin, thus correlating with microscopic appearance of elongated, curved and widened bacteria. Bacteria that had survived exposure to 16 mg/L for 48 h showed low-grade resistance in comparison with those not exposed to antibiotic. Thus, the mechanism of the inoculum effect was expressed as an enlarging bacterial mass during bacteriostasis, with survival of bacterial populations with low-grade resistance of about two-fold increase in MIC.

Anti-Bacterial Agents↗

A randomized controlled trial of azithromycin versus doxycycline/ciprofloxacin for the syndromic management of sexually transmitted infections in a resource-poor setting.

A randomized controlled trial was carried out to assess the effectiveness of azithromycin versus a standard regimen with doxycycline/ciprofloxacin in the treatment of sexually transmitted infections in a resource-poor environment. Infection with Chlamydia trachomatis was cured in 23/24 (95.8%) of women in the azithromycin arm versus 19/21 (90.5%) in the doxycycline arm (P = 0.6), resulting in three treatment failures. Gonorrhoea was cured in 55/56 (98.2%) women, with one treatment failure in a patient with concomitant C. trachomatis infection. These results indicate that a single oral dose of azithromycin may prove to be a more effective and convenient treatment for sexually transmitted infections in women in a resource-poor environment

Anti-Bacterial Agents↗

Comparative distribution of azithromycin in lung tissue of patients given oral daily doses of 500 and 1000 mg.

OBJECTIVES: The administration of antibacterial agents should be optimized on the basis of their distribution to enhance drug exposure and obtain bacterial eradication. This study examines the pharmacokinetics of azithromycin in plasma, lung tissue and bronchial washing in patients after oral administration of 500 mg versus 1000 mg once daily for 3 days. PATIENTS AND METHODS: Samples of plasma, lung tissue and bronchial washing were obtained from a cohort of 48 patients during open-chest surgery for lung resection up to 204 h after the last drug dose, and assayed for antibiotic concentrations. RESULTS: Azithromycin was widely distributed within the lower respiratory tract and sustained levels of the drug were detectable at the last sampling time in lung tissue. Doubling the dose of the antibiotic resulted in a proportional increase in lung area under the curve (AUC, 1245.4 versus 2514.2 h x mg/kg) and peak tissue concentration (Cmax, 8.93 +/- 2.05 versus 18.6 +/- 2.20 mg/kg). The pharmacodynamic parameter AUC/MIC for susceptible and intermediate strains of Streptococcus pneumoniae (MICs 0.5 and 2 mg/L, respectively) increased after administration of the 1000 mg schedule compared with 500 mg (AUC/MIC0.5 2414 versus 1144 and AUC/MIC2 2112 versus 814.1 h x mg/kg, respectively) in pulmonary tissue. CONCLUSIONS: Lung exposure to azithromycin is increased proportionally by doubling the dose, which results in a predictable pharmacokinetic behaviour of the drug in the lower respiratory tract.

Anti-Bacterial Agents↗

Biofilm formation by Pseudomonas aeruginosa: role of the C4-HSL cell-to-cell signal and inhibition by azithromycin.

OBJECTIVES: In Pseudomonas aeruginosa, biofilm formation is controlled by a cell-to-cell signalling circuit relying on the secretion of 3-oxo-C12-HSL and C4-HSL. Previous studies suggested that C4-HSL plays no significant role in biofilm formation. However the wild-type PAO1 strain PAO-BI, used as a control in these studies is itself impaired in the production of C4-HSL. We wondered therefore whether the role of C4-HSL in biofilm formation might have been underestimated, and whether azithromycin inhibits biofilm formation by interfering with cell-to-cell signalling. METHODS: We used isogenic mutants of wild-type PAO1 strains PAO-BI and PT5 in a static biofilm model. Biofilm formation was quantified using Crystal Violet staining and exopolysaccharide measurements. RESULTS: Wild-type strain PAO-BI, as a result of its reduced C4-HSL secretion, produced 40% less biofilm compared with the wild-type PAO1 strain PT5. Using isogenic mutants of strain PT5 we have shown that whereas a lasI mutant (deficient in 3-oxo-C12-HSL) produced similar amounts of biofilm to the wild-type, a rhlI mutant (deficient in C4-HSL) produced 70% less biofilm. In the latter strain, biofilm formation could be restored by addition of exogenous C4-HSL. Azithromycin, known to reduce the production of both 3-oxo-C12-HSL and C4-HSL, inhibited biofilm formation of wild-type PT5 by 45%. This inhibition could be reversed by the addition of both cell-to-cell signals. CONCLUSIONS: Our results indicate that C4-HSL also plays a significant role in biofilm formation. Furthermore, we demonstrate the potential of using cell-to-cell signalling blocking agents such as azithromycin to interfere with biofilm formation.

4-Butyrolactone↗

Emergence of a 23S rRNA mutation in Mycoplasma hominis associated with a loss of the intrinsic resistance to erythromycin and azithromycin.

OBJECTIVES: Mycoplasma hominis is intrinsically resistant to 14- and 15-membered macrolides and to the ketolide telithromycin but is susceptible to josamycin, a 16-membered macrolide, and lincosamides. The aim of our study was to investigate the in vitro development of macrolide resistance in M. hominis and to study the impact of ribosomal mutations on MICs of various macrolides and related antibiotics. METHODS: Selection of macrolide-resistant mutants was performed by serial passages of M. hominis PG21 in broth medium containing subinhibitory concentrations of clindamycin, pristinamycin, quinupristin/dalfopristin and telithromycin. Stepwise selection of josamycin-resistant mutants was performed onto agar medium containing increasing inhibitory concentrations of josamycin. Resistant mutants were characterized by PCR amplification and DNA sequencing of 23S rRNA, L4 and L22 ribosomal protein genes. RESULTS: Various mutations in domain II or V of 23S rRNA were selected in the presence of each selector antibiotic and were associated with several resistance phenotypes. Josamycin was the sole antibiotic that selected for single amino acid changes in ribosomal proteins L4 and L22. Unexpectedly, the C2611U transition selected in the presence of clindamycin and the quinupristin/dalfopristin combination was associated with decreased MICs of erythromycin, azithromycin and telithromycin, leading to a loss of the intrinsic resistance of M. hominis to erythromycin and azithromycin. CONCLUSIONS: Ribosomal mutations were associated with resistance to macrolides and related antibiotics in M. hominis. Some mutants showed a loss of the intrinsic resistance to erythromycin and azithromycin.

Anti-Bacterial Agents↗

Azithromycin iv pharmacodynamic parameters predicting Streptococcus pneumoniae killing in epithelial lining fluid versus serum: an in vitro pharmacodynamic simulation.

OBJECTIVES: To investigate the azithromycin pharmacodynamic parameters predicting bacterial killing in epithelial lining fluid (ELF) versus serum against macrolide-susceptible and -resistant Streptococcus pneumoniae isolates (with different resistance genotypes), through the simulation of concentrations achieved after a 500 mg intravenous (iv) once a day regimen. METHODS: An in vitro computer-controlled pharmacodynamic simulation of human azithromycin concentrations in serum and ELF was carried out, and colony counts were determined over 24 h. Four strains with MIC values (mg/L) of 0.5 [mef(A) and erm(B) negative], 2 [mef(A) positive and erm(B) negative], 8 [mef(A) positive and erm(B) negative] and 256 [mef(A) negative and erm(B) positive] were used. RESULTS: Significant (P < 0.05) azithromycin antibacterial activity versus antibiotic-free controls was found in serum and ELF against the susceptible and mef(A) positive strains, but not against the erm(B) positive strain. AUC(0-24)/MIC values around or higher than 25 were needed to achieve (time to 99.9% reduction of initial inocula of around 6 h) and maintain (24 h inocula reduction > or =3 log(10)cfu/mL) bactericidal activity without regrowth. This was achieved only with the susceptible strain in serum, but also with the mef(A) positive strain exhibiting an MIC of 2 mg/L in ELF. CONCLUSIONS: The results of this study support that the suggested breakpoint for susceptibility (< or =2 mg/L) may be adequate to predict S. pneumoniae eradication with ELF but not with serum concentrations obtained after a 500 mg iv once a day regimen.

Anti-Bacterial Agents↗

Treatment of cyclosporin-induced gingival hyperplasia with azithromycin.

BACKGROUND: Gingival hyperplasia is a known complication of cyclosporin therapy. Although plaque control has been shown to be of benefit, gingival surgery is occasionally necessary. The aim of this study was to review the effect of a short-course therapy with azithromycin in renal transplant patients with cyclosporin-induced gingival hyperplasia. METHODS: Thirty-eight patients received 500 mg/day of azithromycin for 3 consecutive days. The degree of gingival hyperplasia was classified as: 0, no gingival overgrowth; 1, mild overgrowth; 2, moderate overgrowth, and 3, severe overgrowth. Gingival bleeding and evolution of gingival hyperplasia were determined at 0 (pretreatment), 7, 30, 90 and 180 days. Cyclosporin, serum creatinine and ALT levels were simultaneously determined on the same days. RESULTS: Seven patients were excluded, leaving a total of 31 included in the trial. Eleven had a score of 3, 17 a score of 2, and 3 a score of 1. The degree of gingival hyperplasia was unrelated to the dose and levels of cyclosporin. Gingival hyperplasia improved in all patients (P < 0.001, Friedman test). The degree of improvement was better when the degree of hyperplasia was lower. In 27 patients gingival hyperplasia remained absent 6 months later, 3 patients required a second course of treatment, and another required gingival surgery. Gingival bleeding, present in 28 patients when diagnosed, disappeared in all cases in 2.2 +/- 1.2 (1-7) days. No adverse effects were observed. Cyclosporin, serum creatinine, and ALT levels were not affected by treatment. CONCLUSIONS: Azithromycin improves cyclosporin-associated gingival hyperplasia, especially when administered early in the process.

Adult↗

Oral rifampin plus azithromycin or clarithromycin to treat osteomyelitis in rabbits.

A rabbit model for Staphylococcus aureus osteomyelitis was used to compare 28-day combination antibiotic therapy using oral rifampin (40 mg/kg, twice daily) plus oral azithromycin (50 mg/kg, once per day), oral clarithromycin (80 mg/kg, twice daily), or parenteral nafcillin (30 mg/kg, four times daily). The left tibial metaphysis of New Zealand White rabbits was infected with Staphylococcus aureus. Grades 3 to 4 osteomyelitis (according to the Cierny-Mader classification system) development in the rabbits was confirmed radiographically. After antibiotic therapy regimens of 28 days, all tibias from controls that were infected but left untreated (n = 10) revealed positive cultures for Staphylococcus aureus at a mean concentration of 2.8 x 10(4) colony forming units/g bone. The rifampin plus clarithromycin (n = 15) and rifampin plus azithromycin (n = 15) groups showed significantly lower percentages of positive Staphylococcus aureus infection (20% and 13.3%, respectively) and bacterial concentrations (3.5 x 10(1) and 1.75 x 10(1) colony forming units/g bone, respectively). The osteomyelitic tibias of the nafcillin plus rifampin treated group (n = 7) showed no detectable Staphylococcus aureus infection (significantly lower than controls). The differences observed for bone bacterial concentrations and sterilization percentages between the antibiotic treated groups were not statistically significant. Although fluoroquinolones (including ofloxacin and ciprofloxacin) are the agents usually prescribed with rifampin, increasing resistance has been observed. Although macrolides traditionally are not used in the treatment of osteomyelitis, the results of this study indicate that azithromycin and clarithromycin may be attractive partners for rifampin for the treatment of Staphylococcus aureus osteomyelitis in humans.

Administration, Oral↗

Omeprazole plus azithromycin and either amoxicillin or tinidazole for eradication of Helicobacter pylori infection.

GOALS: To establish whether omeprazole plus azithromycin in association with either amoxicillin or tinidazole is effective in curing Helicobacter pylori infection in dyspeptic patients. BACKGROUND: Many antibiotics in combination with antisecretory drugs have been used in an attempt to find the optimal regimen for eradication of H. pylori. Azithromycin is a macrolide that achieves high concentrations in gastric tissue after a single 500-mg oral dose. STUDY: A total of 160 consecutive symptomatic patients with H. pylori received omeprazole 20 mg twice daily for 1 week, azithromycin 500 mg/d for 3 days, and were randomly assigned to either amoxicillin 1 g twice daily (OAzAm group, n = 80) for 1 week or tinidazole 500 mg twice daily for 3 days (OAzT group, n = 80). H. pylori status was assessed by rapid urease test and histology at entry and by histology and (13)C-urea breath test after the end of the therapy. RESULTS: H. pylori was eradicated in 62.5% of patients in the OAzAm group (intention to treat [ITT] 62.5%) and in 71.2% of patients in the OAzT group (ITT 71.2%). CONCLUSIONS: Although the compliance was excellent and the side effects negligible, the regimens used were partially effective for the eradication of H. pylori.

Adult↗

A multicenter, open label trial of azithromycin for the treatment of children with acute otitis media.

OBJECTIVE: In this multicenter, open label trial the investigators evaluated the efficacy and safety of azithromycin suspension administered once daily for 5 days for the treatment of clinically and bacteriologically established acute otitis media. METHODS: Two hundred eligible children with acute otitis media from 10 US centers were treated with 10 mg/kg of azithromycin oral suspension on Day 1, followed by 5 mg/kg once daily for the next 4 days. Tympanocentesis and subsequent culture of middle ear effusion were performed at baseline. Clinical efficacy was evaluated on Days 6, 11 and 30. RESULTS: Analysis of clinical efficacy in evaluable patients 11 days after the initiation of therapy showed that the rate of satisfactory responses (cured or improved) ranged from 79.6 to 82.4% in patients infected with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. Satisfactory clinical response at Day 30 was reported in 70% of evaluable patients, and eradication of S. pneumoniae, H. influenzae and M. catarrhalis was presumed in 64 to 73%. Relapses occurred in 14% of the evaluable patients. Among the treated patients 8.5% reported mild or moderate side effects. CONCLUSION: Azithromycin is an effective, safe and well-tolerated treatment for children with acute otitis media.

Acute Disease↗

Comparison of two dosages of azithromycin for three days versus penicillin V for ten days in acute group A streptococcal tonsillopharyngitis.

BACKGROUND: Three-day, 10 mg/kg/day azithromycin (AZM) studies in pediatric acute group A streptococcal tonsillopharyngitis have shown contradictory bacteriologic results. This study investigates the efficacy and tolerability of two dosages of 3-day azithromycin (20 mg/kg/day and 10 mg/kg/day) compared with 10-day penicillin V. METHODS: This was a prospective, comparative, randomized, multicenter trial. Children were scheduled to return for visits at 14 days (main end point) and 1 month after the onset of treatment for clinical and bacteriologic assessment. Molecular tools were used to compare pre- and posttreatment group A beta-hemolytic Streptococcus (GABHS) isolates. RESULTS: Between November, 1997, and July, 1998, 501 patients (169 AZM 10 mg, 165 AZM 20 mg, 167 penicillin V) between 2 and 12 years old were enrolled; 500 were assessable for safety, 469 for intent to treat analysis and 420 for efficacy in the per protocol analysis. Before treatment 25 (7.9%) of 315 GABHS stains isolated from patients receiving AZM were resistant to this compound. On Day 14 pretreatment GABHS were eradicated from 78 (57.8%) of the 135 children receiving the AZM 10 mg regimen, 131 (94.2%) of the 139 receiving AZM 20 mg and 123 (84.2%) of the 146 taking penicillin. One month after the outset of treatment, bacteriologic relapses were observed in 40.5% (n = 30) of the children receiving AZM 10 mg, 14.8% (n = 18) of children taking AZM 20 mg and 13.2% (n = 15) of those treated with penicillin V. AZM 20 mg/kg/day was statistically superior to AZM 10 mg/kg/day microbiologically on Day 14 (P = 0.0001) and Day 30 (P = 0.0001) and clinically on Day 14 (P = 0.0035). AZM 20 mg/kg/day was statistically equivalent both microbiologically and clinically to standard therapy with penicillin V at all endpoints. The incidence of treatment-related adverse events was similar in the two azithromycin groups [AZM 10 mg, 31 of 169 (18.3%); AZM 20 mg, 37 of 164 (23%)] but significantly higher than those observed in the penicillin V group [5 of 166 (3%); P < 0.0001]. Most treatment-related adverse events were gastrointestinal and of mild-to-moderate severity. Fourteen patients withdrew from the trial because of adverse events (1 in the penicillin V group, 7 in the AZM 10 mg group and 6 in the AZM 20 mg group). CONCLUSION: This is the first study to demonstrate a daily dose-dependent difference in microbiologic efficacy of a regimen; 3-day AZM 20 mg/kg/day is a more effective regimen than 3-day AZM 10 mg/kg/day for pediatric GABHS tonsillopharyngitis.

Administration, Oral↗

Reduced susceptibility to azithromycin and high percentages of penicillin and tetracycline resistance in Neisseria gonorrhoeae isolates from Manaus, Brazil, 1998.

BACKGROUND: The identification of Neisseria gonorrhoeae isolates resistant to antimicrobial agents currently recommended for the treatment of gonococcal infections continues to escalate globally. Thus, in some areas, resistance to fluoroquinolone drugs is commonplace; several reports document resistance to third-generation cephalosporins, and the sporadic isolation of spectinomycin-resistant isolates continues unabated. Gonococcal resistance to azithromycin, an antibiotic used for the primary treatment of gonococcal infections in some Latin American countries, also has been described. Because the prevalence of resistant isolates is insufficiently documented in many areas of Latin America, the efficacy of locally recommended therapies for gonococcal infections is often unknown. GOAL: To determine the antimicrobial susceptibility and strain types of N gonorrhoeae isolates collected in Manaus, Brazil. These data will establish antimicrobial susceptibility baseline data for the region as a reference point for future surveillance. STUDY DESIGN: Consecutive N gonorrhoeae isolates from urethral and endocervical specimens were collected and examined for identity, antimicrobial susceptibility, and strain type (plasmid content, tetM type, auxotype, and serovar). RESULTS: Most of the isolates (65/81; 85.2%) were resistant to tetracycline, penicillin, or both, with the majority (n = 62) carrying plasmid-mediated resistance to tetracycline (tetracycline-resistant N gonorrhoeae [TRNG]). All of the TRNG contained the Dutch-type tetM plasmid, and 18 were A/S class NR/IA-02. Penicillinase-producing N gonorrhoeae comprised 8.2% (7/81) of the isolates. Of these seven isolates, four also were TRNG, and two carried chromosomal resistance to tetracycline. The isolates were susceptible to ciprofloxacin, spectinomycin, and ceftriaxone. However, 23 isolates were characterized by reduced susceptibility to azithromycin (MIC, 0.25-0.5 microg/ml), and one isolate had reduced susceptibility to ciprofloxacin (MIC, 0.25 microg/ml). CONCLUSIONS: This study supports the continued use of third-generation cephalosporins, spectinomycin, and fluoroquinolone drugs for the primary treatment of gonococcal infections in Manaus. The occurrence of isolates with reduced susceptibility to azithromycin and ciprofloxacin underscores the importance of ongoing antimicrobial susceptibility monitoring to support decisions regarding appropriate drugs for the treatment of gonococcal infections.

Anti-Bacterial Agents↗

High percentages of resistance to tetracycline and penicillin and reduced susceptibility to azithromycin characterize the majority of strain types of Neisseria gonorrhoeae isolates in Cuba, 1995-1998.

BACKGROUND: In many regions the susceptibility of Neisseria gonorrhoeae isolates to antimicrobial agents is rarely tested. The Gonococcal Antimicrobial Surveillance Program (GASP) in Cuba was established as part of a larger regional GASP program to facilitate the collection and reporting of antimicrobial susceptibility data for N gonorrhoeae isolates. GOAL: The goal was to retrospectively determine the antimicrobial susceptibility and molecular epidemiology of 91 isolates of N gonorrhoeae isolated from 11 centers in Cuba. STUDY DESIGN: Isolates of N gonorrhoeae were collected and presumptively identified from 11 Cuban provincial health centers. They were then forwarded to the National Laboratory of Pathogenic Neisseria Havana for confirmatory identification and were subsequently analyzed at the Center for GASP in Ottawa. Isolates were tested for susceptibility to penicillin, tetracycline, spectinomycin, ceftriaxone, ciprofloxacin, and azithromycin by the agar dilution method. To establish baseline data for molecular epidemiologic profiles, the auxotype (A), serovar (S), plasmid content (P), and TetM type of the isolates were determined. Certain A/S/P classes were further analyzed by pulsed field gel electrophoresis (PFGE). RESULTS: High percentages of the 91 N gonorrhoeae isolates were resistant to penicillin (68%) and tetracycline (83.5%), with 56% being penicillinase-producing (PPNG) and 64% carrying plasmid-mediated tetracycline resistance (TRNG; 50% were PP/TRNG). An additional 14% of the isolates carried chromosomal resistance (CMRNG) to either tetracycline or penicillin or both antibiotics. All isolates were susceptible to spectinomycin, ceftriaxone, and ciprofloxacin. However, nine isolates were resistant to azithromycin (MIC, > or = 1.0 microgram/ml), and 43 other isolates displayed reduced susceptibility to this antibiotic (MIC, 0.25-0.5 microgram/ml). Although a total of 21 different A/S classes were identified, most of the isolates (61) belonged to three A/S classes: NR/IA-6 (35 isolates), NR/IB-1 (15 isolates), and P/IA-6 (11 isolates). Thirty-two of 45 PP/TRNG were A/S class NR/IA-6, and nine of the P/IA-6 isolates were TRNG. By contrast, most of A/S class NR/IB-1 (8) were CMRNG. PFGE analysis following digestion with NheI or SpeI further clustered the isolates into separate groups. CONCLUSIONS: This study demonstrates high percentages of N gonorrhoeae isolates with penicillin and tetracycline resistance in Cuba. As has been noted in other studies in the Caribbean region and Latin America, resistance and reduced susceptibility to azithromycin are developing as emerging problems. Since penicillin and tetracycline continue to be widely used for the treatment of gonococcal infections in Cuba, this study indicates the importance of antimicrobial susceptibility surveillance so that effective antibiotics may be recommended for treatment of gonococcal infections.

Anti-Bacterial Agents↗

Defining the optimum treatment regimen for azithromycin in acute tonsillopharyngitis.

Pharyngitis is one of the most common infectious diseases affecting children. Group A streptococci are the leading bacterial cause of pharyngitis in children and adults. Because inappropriate antibiotic treatment for pharyngitis is becoming a major issue, only true group A beta-hemolytic streptococcus (GABHS) infections, proven by rapid antigen test or culture, should be treated with antibiotics. GABHS pharyngitis is often a mild and self-limiting infection in the absence of antimicrobial therapy. However, antimicrobial treatment must be administered to eradicate the pathogen from the throat, limit the spread of the infection and prevent possible progression to rheumatic fever, suppurative disease or toxin-mediated complications. Penicillin V for 10 days is the standard therapy and is effective in the management of GABHS pharyngitis. However, there are drawbacks to penicillin V therapy, including the length of the dosing regimen, which are leading to decreasing penicillin prescription rates in many countries. In addition bacteriologic treatment failures have been documented in up to 35% of GABHS patients treated with penicillin V, particularly in children <6 years old. A number of mechanisms may be responsible for these failures, but poor compliance with the standard 10-day penicillin treatment is likely to be a major factor. There is growing evidence to suggest that children with GABHS pharyngitis can be effectively treated with non-penicillin V antibiotics, which have the advantage of simpler and shorter dosing regimens compared with penicillin V. Among the antibiotics that have been tested clinically, azithromycin is the most widely studied. A total dose of 60 mg/kg azithromycin, given either as 12 mg/kg once daily for 5 days or 20 mg/kg once daily for 3 days, provides the best rate of GABHS eradication. Thus a total dose of 60 mg/kg azithromycin given during 3 or 5 days constitutes an alternative treatment to standard penicillin therapy in cases of penicillin hypersensitivity, when patient nonadherence to a 10-day penicillin regimen is suspected or for patients who fail therapy with a beta-lactam.

Azithromycin↗

Pharyngeal Gonorrhea in female sex workers: Response to a single 2-g dose of azithromycin.

OBJECTIVES: A sharp increase in the incidence of gonorrhea has been observed in Tel Aviv, Israel, since 1999. Almost one half of interviewed patients admitted contracting the infection from a sex worker. In two thirds of the cases, oral sex (fellatio) was the most probable route of acquiring the disease. In the current study, we assessed the prevalence of pharyngeal gonorrhea among sex workers in Tel Aviv and evaluated the efficacy of a single 2-g dose of azithromycin in eradicating the infection. METHODS: Throat specimens were obtained for gonococcal culture from 301 female sex workers practicing in brothels. A questionnaire covering demographic and sexual behavior information was administered to all participants, and a single 2-g dose was administered orally under supervision. Women with positive cultures were reexamined a week later for eradication of Neisseria gonorrhoeae. RESULTS: N gonorrhoeae was isolated from 27 women (9%). The median age of women with pharyngeal gonorrhea was 23 years (range, 18-32 years); 85% were born in former Soviet Union (mostly Russia, Ukraine, Moldavia). Regular condom use in vaginal sex was reported by 88% of the participants, whereas only 60% reported always using condoms in oral sex. All isolates were susceptible to azithromycin (MIC < or = 0.5 microg/ml). Gonococci were eradicated in 20/21 individuals (95%). CONCLUSION: A high carriage rate of gonococci in the throat and a low rate of condom use in oral sex were documented among sex workers in Tel Aviv. A single 2 g dose of azithromycin was very effective in eradicating gonococci from the throat.

Adolescent↗