Chikungunya virus virus-like particle vaccine is well tolerated and immunogenic in chikungunya seropositive individuals.

In a phase 2 safety and immunogenicity study of a chikungunya virus virus-like particle (CHIKV VLP) vaccine in an endemic region, of 400 total participants, 78 were found to be focus reduction neutralizing antibody seropositive at vaccination despite being ELISA seronegative at screening, of which 39 received vaccine. This post hoc analysis compared safety and immunogenicity of CHIKV VLP vaccine in seropositive (n = 39) versus seronegative (n = 155) vaccine recipients for 72 weeks post-vaccination. There were no differences in solicited adverse events, except injection site swelling in 10.3% of seropositive versus 0.6% of seronegative recipients (p = 0.006). Baseline seropositive vaccine recipients had stronger post-vaccination luciferase neutralizing antibody responses versus seronegative recipients (peak geometric mean titer of 3594 and 1728, respectively) persisting for 72 weeks, with geometric mean fold increases of 3.1 and 13.2, respectively. In this small study, CHIKV VLP vaccine was well-tolerated and immunogenic in individuals with pre-existing immunity. ClinicalTrials.gov Identifier: NCT02562482.

Immunogenicity of partial doses of live oral cholera vaccine CVD 103-HgR in children in the United States.

In a phase 4, placebo-controlled, double-blind, multi-center study performed to assess the immunogenicity of a single oral dose of live, attenuated cholera vaccine, volunteers aged 2-17 years were randomized 6:1 to receive 1 × 109 colony forming units of PXVX0200 or placebo. In the subset of subjects who consumed < 80 % of the vaccine dose, seroconversion rates were calculated and stratified by amount consumed. Of 468 subjects dosed, a subset of 33 (7 %) received < 80 % of the vaccine dose. SVA seroconversion occurred in 75.8 % of these subjects, including 100 % (7/7) of those who took 50-80 % and 69.2 % (18/26) of those who took < 50 %, versus 98.5 % of those who consumed 80 % or more. Vaccination with PXVX0200 produced an immune response in most children who received partial dosing. Since SVA seroconversion is a strong correlate of protection, PXVX0200 may protect against cholera infection in children who ingest only part of the vaccine dose.

Central Nervous System Coccidioidomycosis in Children: A Retrospective Case Series.

BACKGROUND: Published literature on central nervous system (CNS) coccidioidomycosis in children is limited. Here we describe a large case series of pediatric CNS coccidioidomycosis from a tertiary care center in an endemic region. METHOD: This is a retrospective case review of patients ≤21 years old with a diagnosis of CNS coccidioidomycosis from January 1, 2000, to December 31, 2018. RESULTS: Thirty patients (median age 10.8 years) were identified and most (93%) were previously healthy. Fever (90%), headache (70%), vomiting (53%), and fatigue (57%) were the most common presenting clinical manifestations, with focal neurological signs/symptoms present in 14 (47%). The initial serum Coccidioides compliment fixation (CF) titer was ≤ 1:8 in 33%. Most patients had extra-axial brain involvement (83%) and seven (23%) had associated spinal cord disease. Shunt placement was required in 70% and 62% required revision. Fluconazole was the initial treatment in 22 (73%), with treatment failure occurring in 50%. Most patients (77%) stabilized and were maintained on suppressive therapy, 4 (13%) experienced relapses and/or progressive disease, and one (3%) died, while long-term neurological complications occurred in 17%. CONCLUSIONS: CNS coccidioidomycosis is an uncommon and sometimes devastating complication of disseminated coccidioidomycosis. Many patients present with relatively low CF titers and hydrocephalus is common. Fluconazole treatment failures are common, and management remains difficult despite recent advances in therapy. Most patients do well once the disease is stabilized and require lifelong therapy. Newer therapeutic agents are needed.

Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial.

BACKGROUND: Chikungunya virus (CHIKV) disease is an ongoing public health threat. We aimed to evaluate the safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted formulation of a CHIKV virus-like particle (VLP) vaccine. METHODS: This randomised, double-blind, parallel-group, phase 2 trial was conducted at three clinical trial centres in the USA. Eligible participants were healthy CHIKV-naïve adults aged 18-45 years. Participants were stratified by site and randomly assigned (1:1:1:1:1:1:1:1) to one of the eight vaccination groups using a block size of 16. Group 1 received two doses of unadjuvanted PXVX0317 28 days apart (2 × 20 µg; standard); all other groups received adjuvanted PXVX0317: groups 2-4 received two doses 28 days apart (2 × 6 µg [group 2], 2 × 10 µg [group 3], or 2 × 20 µg [group 4]; standard); group 4 also received a booster dose 18 months after the first active injection (40 µg; standard plus booster); groups 5-7 received two doses 14 days apart (2 × 6 µg [group 5], 2 × 10 µg [group 6], or 2 × 20 µg [group 7]; accelerated); and group 8 received one dose (1 × 40 µg; single). The primary endpoint was the geometric mean titre of anti-CHIKV neutralising antibody on day 57 (28 days after the last vaccination), assessed in the immunogenicity-evaluable population. Additionally, we assessed safety. This trial is registered at ClinicalTrials.gov, NCT03483961. FINDINGS: This trial was conducted from April 18, 2018, to Sept 21, 2020; 468 participants were assessed for eligibility. Of these, 415 participants were randomly assigned to eight groups (n=53 in groups 1, 5, and 6; n=52 in groups 2 and 8; n=51 in groups 3 and 7; and n=50 in group 4) and 373 were evaluable for immunogenicity. On day 57, serum neutralising antibody geometric mean titres were 2057·0 (95% CI 1584·8-2670·0) in group 1, 1116·2 (852·5-1461·4; p=0·0015 vs group 1 used as a reference) in group 2, 1465·3 (1119·1-1918·4; p=0·076) in group 3, 2023·8 (1550·5-2641·7; p=0·93) in group 4, 920·1 (710·9-1190·9; p<0·0001) in group 5, 1206·9 (932·4-1562·2; p=0·0045) in group 6, 1562·8 (1204·1-2028·3; p=0·14) in group 7, and 1712·5 (1330·0-2205·0; p=0·32) in group 8. In group 4, a booster dose increased serum neutralising antibody geometric mean titres from 215·7 (95% CI 160·9-289·1) on day 547 to 10 941·1 (7378·0-16 225·1) on day 575. Durability of the immune response (evaluated in groups 1, 4, and 8) was shown up to 2 years. The most common solicited adverse event was pain at the injection site, reported in 12 (23%) of 53 participants who received the unadjuvanted vaccine (group 1) and 111 (31%) of 356 who received the adjuvanted vaccine. No vaccine-related serious adverse events were reported. INTERPRETATION: PXVX0317 was well tolerated and induced a robust and durable serum neutralising antibody immune response against CHIKV up to 2 years. A single 40 µg injection of adjuvanted PXVX0317 is being further investigated in phase 3 clinical trials (NCT05072080 and NCT05349617). FUNDING: Emergent BioSolutions.

Neonatal Coccidioidomycosis: A Single-center Experience and Review of the Literature.

BACKGROUND: Coccidioidomycosis is common in adult and pediatric populations living in endemic areas of the United States but has rarely been reported in neonates. We reviewed recent cases of neonatal coccidioidomycosis treated at a tertiary care children's hospital in an endemic area and compared them with previously reported cases in the literature. METHODS: We performed a retrospective chart review of infants 1 month old or less hospitalized with a diagnosis of coccidioidomycosis from January 1, 2014, to December 31, 2019. Additionally, we performed a literature review of all reported cases of neonatal coccidioidomycosis over the past 7 decades through PubMed. Infants born to mothers with confirmed or suspected active coccidioidomycosis were excluded. RESULTS: Three cases of neonatal coccidioidomycosis were identified at our institution. Each presented in a unique manner and had an alternative diagnosis at the time of initial presentation. Two patients had negative coccidioidal screening tests upon admission but later seroconverted. All patients had extrapulmonary involvement, and all recovered after appropriate treatment. A review of the literature reveals that the presentations and outcomes of neonatal coccidioidomycosis vary widely. CONCLUSIONS: There is significant variability in the presentation of coccidioidomycosis in the neonatal period, and diagnosis may be challenging. In endemic regions, healthcare providers should consider coccidioidomycosis in their differential diagnoses of ill-appearing neonates that do not respond to treatment.

Hydrocephalus in Mexican children with Coccidioidal Meningitis: Clinical, serological, and neuroimaging findings.

BACKGROUND: Coccidioidal meningitis (CM) is a fungal infectious disease that rarely affects children. Even in endemic areas, coccidiomycosis rarely affects the pediatric population. However, 40% of affected children develop hydrocephalus. Here, we describe the clinical, serological, and neuroimaging findings in a series of Mexican children admitted to our neurosurgical service with hydrocephalus and subsequently diagnosed with CM. METHODS: We report a prospective series of pediatric patients with hydrocephalus secondary to CM in an endemic area at the north of Mexico. Our report includes children with CM who were hospitalized from 2015 to 2019 in a regional hospital in Torreón, Coahuila. Clinical evolution was monitored for 1 year after hospital discharge. RESULTS: Our series include five children with CM (2-17-years-old, three female), who were hospitalized for hydrocephalus and developed intracranial hypertension. The most frequent neuroimaging findings were leptomeningeal enhancement (5/5) and basal arachnoiditis (4/5), followed by asymmetric hydrocephalus (3/5), abnormalities in fourth ventricle morphology (3/5), and cerebral vasculitis (2/5). CM was diagnosed by positive serology or pathology studies. All children were initially managed with fluconazole and a shunt was placed for management of hydrocephalus. Four patients recovered without permanent neurological deficits and one subject developed persistent vegetative state. One year after hospital discharge, none of the subjects died. CONCLUSION: This series contributes to the limited number of pediatric CM cases reported in the literature, and describes neuroimaging findings in the pediatric population. The cases here presented show that the identification of Coccidioides as causal agent in pediatric meningitis is crucial for targeted treatment and can affect dramatically neurological prognosis. Furthermore, our report stresses that even in endemic areas pediatric coccidiomycosis represents a diagnostic challenge, which is further exacerbated by the limited availability of resources in these regions. Therefore, a positive immunoglobulin G by enzyme immunoassay is enough for diagnosis of CM in endemic areas without access to CF.

Long-Term Immunogenicity of Live Oral Cholera Vaccine CVD 103-HgR in Adolescents Aged 12-17 Years in the United States.

As part of a phase 4, randomized, double-blind, placebo-controlled trial to assess the immunogenicity and safety of PXVX0200 in children and adolescents aged 2-17 years, a subset of 73 adolescent subjects aged 12-17 years was followed for 2 years after vaccination and had blood collected for antibody assays on days 1, 11, 29, 91, 181, 365, 547, and 730. Endpoints included serum vibriocidal antibody (SVA) seroconversion, defined as a 4-fold or greater rise in antibody titer over baseline; geometric mean titers (GMTs); and geometric mean fold increase (GMFI) over baseline. Serum vibriocidal antibody seroconversion persisted in most subjects, with a rate of 64.5% noted at day 730. Geometric mean titers and GMFI both peaked at day 11 and remained greater than baseline at all time points, including day 730. Vaccination with PXVX0200 produces an immune response which persists for at least 2 years in adolescents aged 12-17 years.

Safety and Immunogenicity of Live Oral Cholera Vaccine CVD 103-HgR in Children Aged 2-5 Years in the United States.

In a phase 4, randomized, placebo-controlled, double-blind, multicenter study, to assess the safety and immunogenicity of live, attenuated cholera vaccine PXVX0200 in children aged 2-5 years in the United States, 172 volunteers were randomized 6:1 to receive a single dose of 1 × 109 colony forming units (CFU) of PXVX0200 or placebo. Immunogenicity endpoints included serum vibriocidal antibody (SVA) levels on days 1, 11, and 29. Safety was assessed by comparing solicited signs and symptoms on days 1-8, unsolicited adverse events through day 29, and serious adverse events (SAEs) through day 181. The SVA seroconversion rates 10 days after immunization were 98.1% and 0% in vaccine and placebo recipients, respectively, and the vaccine seroconversion rate was non-inferior to the 93.5% rate seen in the bridging population of adults aged 18-45 years from a lot consistency study. Most reactogenicity was mild to moderate, and there were no study-related SAEs. PXVX0200 appears safe and immunogenic in children aged 2-5 years.

Safety and Immunogenicity of Live Oral Cholera Vaccine CVD 103-HgR in Children and Adolescents Aged 6-17 Years.

The attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR, redeveloped as PXVX0200, elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera-induced diarrhea in adult volunteer challenge trials but has not been studied in children in developed countries. We performed a phase 4, placebo-controlled, double-blind, multicenter study to assess the safety, immunogenicity, and tolerability of a single, oral dose of PXVX0200 in children and adolescents aged 6-17 years in the United States and bridged immunogenicity to adults aged 18-45 years from a separate lot consistency study. Volunteers were randomized to receive a single dose of 1 × 109 colony forming units (CFU) of PXVX0200 or placebo. Immunogenicity endpoints included SVA levels on days 1, 11, and 29 in volunteers aged 6-17 years and also on days 91 and 181 in volunteers aged 12-17 years. Safety was assessed by comparing solicited signs and symptoms on days 1-8, unsolicited adverse events (AEs) through day 29, and serious AEs through day 181. A total of 374 participants were enrolled, comprising 321 vaccine and 53 placebo recipients. The SVA seroconversion rates 10 days after immunization were 98.6% and 2.1% in vaccine and placebo recipients, respectively, and the vaccine seroconversion rate was non-inferior to the 93.5% rate seen in adults aged 18-45 years. Most reactogenicity was mild to moderate, and there were no vaccine-related serious AEs. The complete dose was consumed in 95.3% and 98.1% of vaccine and placebo recipients, respectively. PXVX0200 appears safe, immunogenic, and well tolerated in children and adolescents aged 6-17 years.

Age-related immunogenicity and reactogenicity of live oral cholera vaccine CVD 103-HgR in a randomized, controlled clinical trial.

Aging is accompanied by a decline in immune function which can lead to decreased responses to vaccines. Attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera diarrhea in volunteer challenge studies but has not been studied in older adults. We evaluated CVD 103-HgR (PXVX0200) in adults age 46-64, compared them to previously studied adults age 18-45, and studied age-related immunogenicity across adults 18-64 years of age. Volunteers were randomized to receive a single dose of 1 × 109 CFU of PXVX0200 or placebo. Immunogenicity endpoints included SVA and anti-cholera toxin (CT) antibody levels on days 1, 11, 29, 91 and 181 and lipopolysaccharide (LPS) and CT-specific IgA and IgG memory B cells on days 1, 91 and 181. Safety was assessed by comparing solicited signs and symptoms on days 1-8 and other adverse events through day 181. 2979 volunteers received vaccine, including 291 age 45-64. Day 11 seroconversion occurred in 90.4% of older adults vs 93.5%% of younger adults and met the endpoint of demonstrating non-inferiority between the two groups. Significant increases in LPS-specific IgG and IgA and CT-specific memory IgG memory B cells were seen at days 91 and 181. There appeared to be a continuous age-related decline in SVA seroconversion and geometric mean titers, but not memory B cell responses, across the 18-64 year age range. Most reactogenicity was mild and was more common in the placebo group. PXVX0200 appears safe and immunogenic in older adults. Clinical Trials Registration: clinicaltrials.gov NCT02100631.

Pediatric Coccidioidomycosis: Case Series From a California Pediatric Infectious Diseases Clinic.

BACKGROUND: Coccidioidomycosis is not as well described in the pediatric population as it is in the adult population. We describe clinical findings, diagnosis and management of coccidioidomycosis in 108 pediatric patients seen in an outpatient clinic in the California Central Valley, an area endemic for coccidioidomycosis. METHODS: We reviewed medical records of a convenience sample of pediatric patients (≤17 years of age) diagnosed with coccidioidomycosis who visited an infectious diseases clinic in Madera, CA, during January 1 to October 1, 2012. We described demographic characteristics, symptoms, diagnostic testing, extent of infection (acute/pulmonary or disseminated), treatment and management. RESULTS: Of 108 patients, 90 (83%) had acute/pulmonary coccidioidomycosis and 18 (17%) had disseminated disease. The median age at diagnosis was 9 years (range, 5 months to 17 years). Only 3 (3%) patients were immunocompromised. Before coccidioidomycosis diagnosis, 72 (82%) patients received antibiotics, and 31 (29%) had at least 1 negative coccidioidomycosis serology at the time of or before diagnosis. Coccidioidomycosis was diagnosed significantly later after symptom onset among patients with disseminated (median, 57 days) than with acute/pulmonary (median, 16 days) disease (p < 0.01). A total of 104 (96%) patients received antifungal therapy, 51 (47%) visited an emergency room and 59 (55%) were hospitalized with a median stay of 44 days (range, 1-272 days). CONCLUSIONS: Substantial acute/pulmonary and disseminated coccidioidomycosis was seen among pediatric patients at this infectious disease clinic in California. In endemic areas, increased coccidioidomycosis awareness and vigilance among families and providers is necessary to facilitate early diagnosis and appropriate management.

Safety and immunogenicity of single-dose live oral cholera vaccine strain CVD 103-HgR in healthy adults age 18-45.

The attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR, re-developed as PXVX0200, elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera diarrhea in volunteer challenge studies. We performed a phase 3, placebo controlled, double blind, multi-center study to further assess the safety, immunogenicity, and lot-to-lot consistency of PXVX0200. Adult volunteers 18-45 years of age were randomized 8:1 to receive a single dose of 1 × 109 CFU of PXVX0200 from three production lots or saline placebo. Immunogenicity endpoints included SVA and anti-cholera toxin (CT) antibody levels on days 1, 11, 29, 91 and 181. Safety was assessed by comparing solicited signs and symptoms on days 1-8, unsolicited adverse events through day 29 and serious adverse events through day 181. A total of 3146 participants were enrolled, including 2795 vaccine and 351 placebo recipients. The SVA seroconversion rates at day 11 were 94% and 4% in the PXVX0200 and placebo recipients, respectively (P < .0001). Cumulative SVA seroconversion occurred among 96% of vaccine recipients. PXVX0200 SVA GMTs peaked on day 11 and remained significantly higher than placebo through day 181 while the fold-rise over baseline in PXVX0200 anti-CT antibody was significantly greater than placebo at every post-vaccination time point. Most reactogenicity was mild and resolved within 1-3 days with headache and diarrhea more frequently reported in PXVX0200 recipients. There were no differences in unsolicited adverse events and no study-related serious adverse events. Immunogenicity and safety endpoints were equivalent between the three production lots. PXVX0200 is immunogenic and well tolerated across multiple production lots. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT02094586.

Epidemiology of Pediatric Coccidioidomycosis in California, 2000-2012.

BACKGROUND: Reported coccidioidomycosis cases have increased in the southwestern US since 2000. However, there are few publications on pediatric coccidioidomycosis. We sought to describe the epidemiology of coccidioidomycosis in the California pediatric population during 2000-2012. METHODS: We reviewed surveillance and hospitalization datasets for years 2000-2012 and death datasets for years 2000-2010 to identify coccidioidomycosis-associated cases, hospitalizations and deaths in pediatric (≤17 years old) California residents. We calculated rates and described demographic characteristics of cases and hospitalized patients and, using Poisson regression, calculated bivariate relative risks to identify potential demographic risk factors. We identified immunocompromising conditions associated with hospitalization and death and calculated hospitalization charges. RESULTS: We identified 3453 cases, 1301 hospitalizations and 11 deaths associated with coccidioidomycosis in the California pediatric population. During 2000-2012, annual case and hospitalized patient rates increased and were highest in males, those in the 12-17 age group, and residents of the California endemic region. Compared with White children, African-American children were significantly more likely to be hospitalized (relative risk = 1.4, P = 0.01). Approximately 12.0% of those hospitalized and 27% of those who died had an immunocompromising condition. Hospitalized patients accrued $149 million in total hospital charges. CONCLUSIONS: Similar to recent increases among adults, reported pediatric coccidioidomycosis cases and hospitalizations have increased in California since 2000, disproportionately affecting certain demographic groups. The burden of coccidioidomycosis among California children emphasizes the need for more awareness and research into this reemerging fungal disease in endemic and nonendemic areas.

Treatment of pediatric refractory coccidioidomycosis with combination voriconazole and caspofungin: a retrospective case series.

BACKGROUND: Coccidioidomycosis is a spectrum of diseases caused by the dimorphic fungi Coccidioides. Current regimens for severe or disseminated disease include fluconazole, itraconazole, or amphotericin; newer triazoles (ie, voriconazole, posaconazole) have been demonstrated to be useful in refractory disease. Previous reported experience with combination triazole and caspofungin therapy has been very limited; however, the utility of this combination for treatment of other invasive fungal diseases suggests potential benefit in refractory coccidioidomycosis. METHODS: We conducted a retrospective review of 9 pediatric patients treated with combination voriconazole and caspofungin (V/C) salvage therapy for refractory coccidioidomycosis at two children's hospitals between January 2000 and June 2012. RESULTS: Nine children with refractory coccidioidomycosis were treated with V/C salvage therapy after failing conventional therapy consisting of a triazole, amphotericin B, or a combination of both. Eight of the 9 patients are currently in remission; 1 patient with central nervous system involvement continues to progress. CONCLUSIONS: We report our positive clinical experience treating medically refractory coccidioidomycosis in the pediatric population with concurrent voriconazole and caspofungin therapy. Additional in vitro and in vivo evaluations are warranted to support the role of V/C salvage therapy for refractory coccidioidomycosis.

Pediatric coccidioidomycosis in central California: a retrospective case series.

BACKGROUND: Coccidioidomycosis, an endemic fungal infection seen throughout the southwestern United States, is not well described in children. METHODS: We performed a retrospective observational study of all children admitted to Children's Hospital Central California with coccidioidomycosis from 1 January 2010 to 1 September 2011. RESULTS: Thirty-three children, aged 6 months to 17 years, were hospitalized during the study period. These included patients with pneumonia (n = 28), pleural effusion (n = 13), pleural empyema (n = 4), lung abscess (n = 7), pericarditis (n = 2), osteomyelitis (n = 5), meningitis/cerebritis (n = 2), and vocal cord infection (n = 1). Mediastinitis, with radiographic evidence of purulence and necrotic/abscessed lymph nodes in the mediastinum, was present in 7 patients (21%) and tended to occur more often in younger children (median age, 3 years [range, 0.5-11 years] vs 7 years [range, 0.6-17 years] for non-mediastinitis patients; P = .10). Seven patients were admitted to the intensive care unit and 10 required surgical intervention. One patient died of meningitis. Hospitalizations were longer for patients with mediastinitis (median, 130 days [range, 58-200 days] vs 43 days [range, 3-273 days for non-mediastinitis patients]; P < .01) and those with maximum coccidioidal complement fixing antibody titers ≥1:128 (median, 174 days [range, 53-273 days] vs 33 days [range, 3-200 days] for those with maximum titers <1:128; P < .01). CONCLUSIONS: Coccidioidomycosis causes a substantial disease burden in the children of central California. Mediastinitis is common and tends to occur in younger children. Patients with mediastinitis or elevated coccidioidal complement fixation titers require longer hospitalizations. Further research is needed on the prevention and treatment of this disease.

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.