Inpatient treatment patterns, outcomes, and costs of skin and skin structure infections because of Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus (SA) is a common bacterial pathogen in skin and skin structure infections (SSSIs). Limited data exist on hospital treatment patterns and costs for SA-SSSIs. METHODS: This retrospective analysis examined the lengths of stay, treatment patterns, and costs of hospitalized patients with an SA-SSSI diagnosis using a nationally representative inpatient database. Patients were selected if they had an ICD-9-CM diagnosis of an SSSI with SA noted between January 2005 and June 2006, received a study antibiotic (ie, intravenous [IV] vancomycin, IV or oral linezolid, and IV daptomycin), and were not in the intensive care unit before receiving a study antibiotic. Generalized linear models assessed predictors of length of stay and costs. Costs are expressed in 2005 US dollars. RESULTS: Thirteen thousand four hundred thirty-three patients met the selection criteria and mean (+/-SD) age was 48.2 (+/-18.3) years. Forty percent of patients received a nonstudy antibiotic before receiving their first study antibiotic. Ninety-five percent were prescribed vancomycin as their first study antibiotic. Study antibiotics were administered for an average of 4.3 days, and 8% of patients switched study antibiotics. Nineteen percent of patients receiving IV linezolid stepped down to oral linezolid. Mean (+/-SD) lengths of hospital stay and costs were 6.1 (+/-6.0) days and $6830 (+/-$7100). In-hospital mortality, switching antibiotics, and diagnoses of selected complications or comorbidities were associated with increased lengths of stay and costs. Younger age, location outside the Northeast, and use of oral linezolid were associated with lower lengths of stay and costs. CONCLUSION: The costs of treating inpatient SA-SSSIs are substantial and vary by patient demographics and treatment characteristics.

Costs of skin and skin structure infections due to Staphylococcus aureus: an analysis of managed-care claims.

OBJECTIVES: The incidence of skin and skin structure infections (SSSIs) due to Staphylococcus aureus (SA) is increasing. The objective of this study was to assess the costs of a treatment episode for SA-SSSIs. METHODS: This retrospective analysis used a managed-care claims database to assess the duration and costs of incident SA-SSSI episodes treated with selected antibiotics (i.v. vancomycin, oral linezolid, and daptomycin, termed 'study antibiotics'). Patients were included if they had an ICD-9-CM diagnosis of an SSSI and SA between January 1, 2002 and December 31, 2005. Treatment episodes began on the date of the first antibiotic and ended when the patient had fourteen consecutive days without a study antibiotic or SSSI hospitalization. Costs, represented by health plan payments for SSSIs and overall, were updated to 2005 US dollars. A generalized linear model (GLM) assessed predictors of costs. RESULTS: A total of 1997 patients met the selection criteria. Mean (+/- SD) age was 46.3 (+/- 12.6) years and 55.9% of patients were male. Average episode length was 24 days, and over 95% of patients received i.v. vancomycin or oral linezolid as their initial study antibiotic. Patients remained on study antibiotics for an average of 16.4 days, and only 5% of patients were switched to another study antibiotic. Mean (+/- SD) overall episode costs were $8865 (+/- $20,003), primarily composed of inpatient and outpatient medical services. Treatment failure (i.e., study antibiotic switching or hospitalization), younger age, a diagnosis of bacteremia, osteomyelitis, or multiple complications during the episode, treatment with daptomycin, and greater Charlson co-morbidity score were significant positive predictors of overall costs. Alternatively, treatment with oral linezolid and hospitalization before the start of the outpatient treatment episode were significant negative predictors of overall costs. Mean (+/- SD) SSSI-related costs were $4551 (+/- $11,058). LIMITATIONS: Medical charts and laboratory test results were not available to confirm SSSI and SA diagnoses, and no information was available regarding antibiotics received in the inpatient setting. CONCLUSIONS: The costs of treating SA-SSSIs are substantial and vary by failure rates, co-morbidities, and type of antibiotic therapy.

Efficacy and safety of 3-day azithromycin versus 5-day moxifloxacin for the treatment of acute bacterial exacerbations of chronic bronchitis.

Antibiotic therapy is of clinical benefit in certain patients with acute exacerbations of chronic bronchitis (AECB). In this randomised, investigator-blinded, multicentre trial, azithromycin (500mg once a day (qd) for 3 days) was compared with moxifloxacin (400mg qd for 5 days) for the treatment of outpatients with AECB (forced expiratory volume in 1s (FEV(1)) >35%). Of 342 patients randomised to either treatment, 169 received azithromycin and 173 received moxifloxacin. The mean age in the azithromycin and moxifloxacin groups was 56.4 years and 55.5 years, respectively. In the intent-to-treat analysis, clinical success rates for azithromycin and moxifloxacin were comparable at Days 10-12 (90% versus 90%, respectively) and Days 22-26 (81% versus 82%, respectively). Among patients who were culture-positive at baseline for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis or Haemophilus parainfluenzae, clinical efficacy for azithromycin versus moxifloxacin at Days 10-12 was 93% versus 84%, respectively, and at Days 22-26 it was 89% versus 73%, respectively. The incidence of at least one treatment-related adverse event (AE) in the azithromycin and moxifloxacin groups was 18.3% and 19.1%, respectively. The most common AEs were diarrhoea, nausea, abdominal pain and vaginitis. Most treatment-related AEs were of mild or moderate severity, with no serious treatment-related AEs. One subject in the moxifloxacin group discontinued treatment owing to a treatment-related AE (precordial pain and dry throat). Compliance with both regimens was >90%. Three-day azithromycin and 5-day moxifloxacin demonstrate comparable efficacy and safety for the treatment of AECB in outpatients.

Penicillin and macrolide resistance in pneumococcal pneumonia: does in vitro resistance affect clinical outcomes?

In vitro resistance to antimicrobial agents is escalating among pathogens responsible for the most serious respiratory tract infections. Some reports have suggested that this has direct clinical implications. Because of penicillin and macrolide resistance in Streptococcus pneumoniae, current guidelines for the initial treatment of respiratory tract infections advocate less reliance on the use of either of these classes of drugs in single-agent therapy. Recent studies that have assessed the impact of beta -lactam and macrolide resistance on clinical outcomes in community-acquired pneumonia fail to provide incontrovertible evidence for a direct link between in vitro resistance and treatment failure. However, there are anecdotal reports of breakthrough bacteremia due to macrolide-resistant pneumococci among patients receiving macrolide therapy, unlike the situation for beta -lactams and penicillin-resistant pneumococci. Continued efforts, including in vitro surveillance, appropriate antibiotic use campaigns, and immunization programs, will be important in limiting the spread of drug-resistant S. pneumoniae.

Comparison of azithromycin and cefadroxil for the treatment of uncomplicated skin and skin structure infections.

In this multicenter, investigator-blind trial, we compared the efficacy and safety of azithromycin and cefadroxil for the treatment of uncomplicated skin and skin structure infections (SSSIs). A total of 296 patients were randomized to receive either azithromycin (500 mg on day 1, followed by 250 mg once a day on days 2 to 5) or cefadroxil (500 mg twice a day for 10 days). Outpatients, ranging in age from 18 to 75 years, with acute uncomplicated SSSIs were enrolled in the study. Clinical and bacteriologic response was assessed between days 10 and 13 (primary end point) and between days 28 and 32. In a modified intent-to-treat analysis, clinical success rates assessed between days 10 and 13 were 97% (111/114) for azithromycin and 96% (101/105) for cefadroxil (P = .717). For azithromycin and cefadroxil, corresponding rates of bacteriologic eradication for Staphylococcus aureus were 94% (64/68) and 86% (60/70), respectively, and for Streptococcus pyogenes, 80% (4/5) and 100% (6/6), respectively. Clinical success rates assessed between days 28 and 32 were 100% (82/82) for azithromycin compared with 90% (75/83) for cefadroxil (P = .007). Corresponding rates of eradication for S aureus were 100% (59/59) versus 89% (56/63), respectively; and for S pyogenes, 100% (4/4) versus 83% (5/6), respectively. The incidence of treatment-related adverse events was similar in the 2 treatment groups. However, 5 of the 139 patients (4%) in the cefadroxil group discontinued therapy because of treatment-related adverse events compared with none of the 152 patients in the azithromycin group (P = .02). Five-day therapy with azithromycin was as effective as 10-day therapy with cefadroxil for treating uncomplicated SSSIs.

High-dose azithromycin versus high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent acute otitis media.

Infants and young children, especially those in day care, are at risk for recurrent or persistent acute otitis media (AOM). There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients. In this double-blind, double-dummy multicenter clinical trial, we compared a novel, high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM. Three hundred four children were randomized; 300 received either high-dose azithromycin (20 mg/kg of body weight once a day for 3 days) or high-dose amoxicillin-clavulanate (90 mg/kg divided twice a day for 10 days). Tympanocentesis was performed at baseline; clinical response was assessed at day 12 to 16 and day 28 to 32. Two-thirds of patients were aged < or =2 years. A history of recurrent, persistent, or recurrent plus persistent AOM was noted in 67, 18, and 14% of patients, respectively. Pathogens were isolated from 163 of 296 intent-to-treat patients (55%). At day 12 to 16, clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients (86 versus 84%, respectively) and for children aged < or =2 years (85 versus 79%, respectively). At day 28 to 32, clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients (72 versus 61%, respectively; P = 0.047) and for those aged < or =2 years (68 versus 51%, respectively; P = 0.017). Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens. The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42%, respectively (P = 0.095). Corresponding compliance rates were 99 and 93%, respectively (P = 0.018). These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM.

A pilot study of single-dose azithromycin versus three-day azithromycin or single-dose ceftriaxone for uncomplicated acute otitis media in children.

BACKGROUND: The pharmacokinetic profile of azithromycin supports its use as single-dose therapy for uncomplicated acute otitis media (AOM) in children. OBJECTIVE: This study was designed to (1) compare the safety of single-dose oral azithromycin, 3 daily doses of oral azithromycin, and a single dose of intramuscular ceftriaxone for the treatment of uncomplicated AOM in children, and (2) provide preliminary efficacy data to support initiation of a larger, comparative trial of single-dose azithromycin for the treatment of uncomplicated acute otitis media in children. METHODS: In this single-center pilot study, children with uncomplicated AOM were randomly assigned to receive single-dose oral azithromycin (30 mg/kg), 3-day oral azithromycin (10 mg/kg once daily), or single-dose intramuscular ceftriaxone (50 mg/kg). Tympanocentesis was performed before administration of the first dose, and clinical response was assessed on days 14-15 and 28-30. RESULTS: Between September 1995 and May 1997, 198 children (mean age, 2.5 years) were enrolled. All of the patients were evaluable for the safety and clinical intent-to-treat (ITT) analyses, and 98 were evaluable for the microbiologic ITT analysis. On day 14-15, rates of clinical success (cure or improvement) for the 3 treatment groups were: 62/64 (97%) for single-dose azithromycin, 60/63 (95%) for 3-day azithromycin, and 61/62 (98%) for single-dose ceftriaxone. On day 28-30, the corresponding clinical success rates were 61/65 (94%), 61/66 (92%), and 62/64 (97%). For the 98 microbiologically evaluable patients, clinical success rates at day 14-15 were 28/30 (93%) for single-dose azithromycin, 31/35 (89%) for 3-day azithromycin, and 33/33 (100%) for single-dose ceftriaxone. On day 28-30, the corresponding clinical success rates were 27/30 (90%), 30/35 (86%), and 32/33 (97%). Treatment-related adverse event rates for single-dose azithromycin, 3-day azithromycin, and single-dose ceftriaxone were 10.6%, 9.1%, and 9.1%, respectively. CONCLUSION: In this pilot study comparing single-dose azithromycin, 3-day azithromycin, and single-dose ceftriaxone for the treatment of uncomplicated AOM in children, no differences were detected among the 3 regimens.

Single-dose azithromycin for acute otitis media: a pharmacokinetic/pharmacodynamic rationale.

The pharmacokinetic (PK) and pharmacodynamic (PD) properties of the azalide azithromycin distinguish it from other antibiotics. The PK profile of azithromycin features high tissue-to-serum ratios, including high concentrations in the middle ear, and a prolonged elimination half-life. These characteristics result from the accumulation of drug within cells and its subsequent slow, sustained release from cells and tissues into the bloodstream. The PD properties of azithromycin include bactericidal activity against key respiratory tract pathogens and a prolonged postantibiotic, or persistent, effect. In addition, white blood cells deliver the drug to infected foci, thereby enhancing local tissue concentrations and improving in vivo efficacy. Recent PK studies in mice suggest that a single, large dose of azithromycin achieves higher tissue concentrations than do multidose regimens. Other studies in animal infection models, in particular, a gerbil model of acute otitis media, have demonstrated improved bacterial eradication when azithromycin is administered as a single dose rather than divided over 2 or 3 days. Taken together, the results from these preclinical studies provide a PK/PD rationale for the use of single-dose azithromycin in the treatment of acute otitis media. Clinical data on the efficacy and safety of single-dose azithromycin for the treatment of acute otitis media in children are presented in 2 accompanying articles in this supplement.