Azithromycin resistance

A recent study of travelers to Thailand comparing azithromycin or ciprofloxacin for the treatment of military personnel who acquired C. jejuni enteritis showed that all the azithromycin-treated patients were cured, while there were two clinical failures in the ciprofloxacin group [261]. Almost 50% of the 44 strains were ciprofloxacin resistant. Recently documented increases in quinolone resistance have been associated with rising levels of azithromycin resistance in Thailand 69% and 31% of 29 C. jejuni isolates were found to be resistant to ciprofloxacin and azithromycin, respectively [262]. Rising levels of azithromycin resistance may compromise the effectiveness of azithromycin for C. jejuni enteritis. 

Coles CL, Mabula K, Seidman JC, Levens J, Mkocha H, Munoz B, et al. Mass distribution of azithromycin for trachoma control is associated with increased risk of azithromycin-resistant Streptococcus pneumoniae carriage in yoimg children 6 months after treatment. Clin Infect Dis... 

Empiric antibiotic therapy is an appropriate approach to traveler s diarrhea. Eradication of the causal microbe depends on the etiologic agent and its antibiotic sensitivity. Most cases of traveler s diarrhea and other community-acquired infections result from enterotoxigenic (ETEC) or enteropathogenic (EPEC) Escherichia coli. Routine stool cultures do not identify these strains primary empiric antibiotic choices include fluoroquinolones such as ciprofloxacin or levofloxacin. Azithromycin may be a feasible option when fluoroquinolone resistance is encountered. 

Azithromycin 1 0 mg/kg x 1 day, 5 mg/kg per day x 4 days 10 mg/kg per day x 3 days or 30 mg/kg single dose (adult dose 500 mg x 1,250 mg x 4 days 500 mg/day x 3 days) Nausea, vomiting, diarrhea, abdominal pain S3 Separate from Al or Mg antacids by 2 hours diarrhea/vomiting more common with singledose regimen 3- or 5-day courses preferred increasing pneumococcal resistance many failures with H. influenzae infection... 

Azithromycin 500 mg once daily 12 mg/kg once daily 5 days Increasing resistance... 

The cornerstone of cholera treatment is fluid replacement. Without treatment, the case-fatality rate for severe cholera is approximately 50%. For cholera, rice-based ORT is better than glucose-based ORT because it reduces the number of stools.21 Patients with significant disease should receive a short antibiotic course, 1 to 3 days, to shorten the duration of illness and decrease the number of stools. Doxycycline 300 mg once daily is the drug of choice. Other antibiotics shown to be effective include erythromycin, azithromycin, trimethoprim-sulfamethoxazole, and ciprofloxacin.2 Antibiotic resistance has been documented in V cholerae since 1977.2 Antibiotic prophylaxis is not warranted. 

Norfloxacin 400 mg or ciprofloxacin 500 mg orally twice daily x 3 days, or trimethoprim-sulfamethoxazole DS tablet orally twice daily x 3 days (in Mexico), or azithromycin 500 mg orally once daily x 3 days (only in areas of high prevalence of quinolone-resistant Campylobacter species, such as Thailand)... 

In uncomplicated exacerbations, recommended therapy includes a mac-rolide (azithromycin, clarithromycin), second- or third-generation cephalosporin, or doxycycline. Trimethoprim-sulfamethoxazole should not be used because of increasing pneumococcal resistance. Amoxicillin and first-generation cephalosporins are not recommended because of /1-lactamase susceptibility. Erythromycin is not recommended because of insufficient activity against H. influenzae. 

The macrolides are orally absorbed but they are acid-labile. They therefore need to be administered in acid-resistant capsules or as acid-resistant esters. The macrolides are widely distributed into all fluids except the CNS. Protein binding is about 90%. They are eliminated via biliary excretion with extensive enterohepatic circulation. Elimination half-lives vary from 1.4 h for erythromycin to 40-60 h for azithromycin. 

Multiply resistant coagulase-negative staphylococci are frequently the cause of postoperative endophtalmitis and require the use of a glycopep-tide (e.g. vancomycin). For topical treatment fusidic acid eye gel, tetracycline or chloramphenicol ointment are available, and can be administered 2 t.d. for 7 days. Trachoma should be treated with an oral macrolide (e.g. a single oral dose of 20 mg/kg azithromycin) or doxycyclin for 3 weeks (for moderate to severe cases). Keratitis needs hourly administration of fortified antibiotic eye drops for 2 weeks. Endophtalmitis needs specialist treatment for 6 weeks. 

When meningitis with penicillin-resistant pneumococcus is suspected, empiric therapy with this regimen is recommended. 4Erythromycin, clarithromycin, or azithromycin (an azalide) may be used. 

Streptococcus pneumoniae Arthritis otitis pneumonia sinusitis If penicillin sensitive ampicillin or penicillin G or V If penicillin resistant vancomycin rifampin A cephalosporin erythromycin azithromycin clarithromycin imipenem meropenem a fluoroquinolone trimethoprim-sulfamethoxazole... 

Resistance to erythromycin is becoming a serious clinical problem. For example, most strains of staphylococci in hospital isolates are resistant to this drug. Several mechanisms have been identified (1) the inability of the organism to take up the antibiotic (2) a decreased affinity of the 50S ribosomal subunit for the antibiotic resulting from the methylation of an adenine of the 23S bacterial ribosomal RNA and (3) presence of a plasmid-associated erythromycin esterase. Both clarithromycin and azithromycin show cross-resistance with erythromycin. 

Both azithromycin and clarithromycin have been used for various bacterial infections for a number of years. Within the last decade, resistance has emerged to a range of antibacterials, including the macrolides, arising from methylation of an adenine in the 23S ribo-somal RNA target site, which prevents binding (146). The invention of the ketolides [e.g., telithromycin (115)] overcomes MLSb resistance by removing the L-cladinose moiety at position 3 the exposed hydroxyl is also oxi-... 

Alternative or reserve drugs are used where there are problems of drug intolerance and bacterial resistance. They are in this class because of either greater toxicity or of lesser efficacy and include ethionamide (gastrointestinal irritation, allergic reactions), capreomycin (nephrotoxic), and cycloserine (effective but neurotoxic). Quinolone antibiotics such as ciprofloxacin and the more recently introduced macrolides such as clarithromycin and azithromycin also have useful activity against mycobacteria. 

Altschuler EL. Azithromycin, the multidrug-resistant protein, and cystic fibrosis. Lancet 1998 351(9111) 1286. 

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