Test Of Cure Research Articles

Ertapenem versus ceftriaxone and metronidazole as treatment for complicated intra-abdominal infections

BackgroundPrompt surgical intervention supplemented by appropriate antimicrobial therapy is usually required for successful treatment of complicated intra-abdominal infections. The objective of this study was to further evaluate the efficacy and safety of ertapenem relative to ceftriaxone/metronidazole as treatment for complicated intra-abdominal infections. MethodsAdult patients with intra-abdominal infections requiring surgery were eligible for this open-label randomized trial comparing ertapenem 1g daily with ceftriaxone 2g daily plus metronidazole 30mg/kg/day. The primary efficacy outcome was the clinical response rate in clinically and microbiologically evaluable participants at the test-of-cure (TOC) visit 2 weeks after discontinuation of therapy. All treated patients were included in the safety analysis. ResultsParticipant demographics, disease characteristics, and duration of therapy in both treatment groups were generally similar. Escherichia coli was the most commonly isolated baseline pathogen, recovered in 52% of cases in each treatment group. Favorable clinical responses were achieved at TOC in 143 (96.6%) of 148 ertapenem recipients and in 146 (96.7%) of 151 ceftriaxone/metronidazole recipients. The frequencies of drug-related adverse events, most commonly nausea, diarrhea, vomiting, and elevated platelet count, were generally comparable in both treatment arms. Four ertapenem recipients (1.8%) and one ceftriaxone/metronidazole recipient (0.4%) experienced serious drug-related adverse events. ConclusionsIn this study, ertapenem and ceftriaxone/metronidazole were comparably effective treatments for adult patients with complicated intra-abdominal infections.

Linezolid eradicates MRSA better than vancomycin from surgical-site infections

Background The purpose of this analysis was to compare the efficacy of linezolid versus vancomycin in patients with suspected or proven gram-positive methicillin-resistant Staphylococcus aureus (MRSA) surgical-site infections. Methods An open-label, randomized, comparator-controlled, multicenter, multinational study was conducted in hospitalized patients. Patients were randomized 1:1 to receive linezolid 600 mg (intravenous [IV] or oral) every 12 hours (n = 66) or vancomycin 1 g every 12 hours IV (n = 69) for 7 to 21 days. Patients were assessed at the test-of-cure (TOC) visit, 7 days after completing therapy. Results Clinical success at TOC was documented in similar proportions of patients treated with linezolid or vancomycin. Of those with MRSA isolated, significantly more patients who received linezolid compared with those who received vancomycin were microbiologically cured (87% vs 48%, respectively; 95% confidence interval 16.51 to 60.27; P = 0.0022). Conclusion Intravenous or oral linezolid was well tolerated and superior to vancomycin in treating patients with MRSA-infected surgical-site infections.

Cefdinir versus levofloxacin in patients with acute rhinosinusitis of presumed bacterial etiology: A multicenter, randomized, double-blind study

Background: Treatment guidelines for acute bacterial rhinosinusitis (ABRS) recommend 10 to 14 days of therapy with high-dose amoxicillin, amoxicillin/clavulanate, cefdinir, cefpodoxime, cefuroxime, a macrolide, or a newer fluoroquinolone, among other agents. Objective: This study compared the clinical efficacy and tolerability of cefdinir and levofloxacin in patients with a diagnosis of acute rhinosinusitis of presumed bacterial origin. Methods: In this multicenter, double-blind, noninferiority study, ambulatory adult patients who had signs and symptoms for >7 to 21 days before the screening visit and radiographic findings consistent with acute rhinosinusitis were randomized to receive cefdinir 600 mg or levofloxacin 500 mg, each once daily for 10 days. Clinical and radiologic response rates were determined at the test-of-cure (TOC) visit, which took place 9 to 14 days after the completion of treatment. Results: Two hundred seventy-one patients (138 cefdinir, 133 levofloxacin) were enrolled and randomized to treatment at 27 study centers in the United States and Poland between November 2003 and March 2004. Of these, 241 (123 cefdinir, 118 levofloxacin) were clinically evaluable. The cefdinir group consisted of 75 women and 48 men, of whom 117 were white and 6 black; their mean (SD) age was 42.5 (14.3) years. The levofloxacin group consisted of 71 women and 47 men, of whom 111 were white and 7 black; their mean age was 40.4 (13.6) years. The 2 groups were similar in terms of presenting signs and symptoms and baseline radiographic findings. The most common presenting symptoms were sinus pain, sinus pressure, and purulent nasal discharge, each of which was reported by ≥89% of patients. Clinical cure rates at the TOC visit in the cefdinir and levofloxacin groups were 83% (102/123) and 86% (101/118), respectively (95% Cl for the difference in cure rates, -12.3 to 7.0). Cefdinir and levofloxacin were comparable in the treatment of infections classified as moderate to severe. The incidence of drug-related adverse events was generally comparable in the 2 treatment groups, although there were significant differences between cefdinir and levofloxacin in the incidence of vaginal moniliasis in women (11% vs 0%, respectively; P = 0.003), drug-related diarrhea (8% vs 1%; P = 0.005), and insomnia (0% vs 4%; P = 0.027). Only 2% of patients discontinued therapy prematurely as a result of a drug-related adverse event. Conclusion: In this population of patients with ABRS, the extended-spectrum cephalosporin cefdinir was as efficacious as the fluoroquinolone levofloxacin, suggesting that cefdinir may be a suitable alternative to the currently recommended fluoroquinolones.

Safety and efficacy of sequential i.v. to p.o. moxifloxacin versus conventional combination therapies for the treatment of community-acquired pneumonia in patients requiring initial i.v. therapy

To compare the efficacy of sequential i.v. to p.o. moxifloxacin with ceftriaxone ± azithromycin ± metronidazole for the treatment of patients with community acquired pneumonia (CAP), a multi-centered, prospective, randomized, open label study was performed. CAP patients were randomized to moxifloxacin (400 mg/d—at least one i.v. dose) or ceftriaxone (at least one dose of 2 g i.v. q.d. followed by cefuroxime 500 mg p.o. b.i.d.) ± azithromycin, ± metronidazole (cephalosporin/macrolide control: CMC). The primary endpoint was clinical response at test-of-cure (TOC) visit. Bacteriological response at TOC was the secondary endpoint. Clinical cure was found in 83.3% (90/108) of moxifloxacin patients and 79.6% (90/113) of control patients. Microbiological responses were 81.8% (18/22) for moxifloxacin and 60.7% (17/28) for CMC patients. Drug-related adverse events occurred in 18.0% of moxifloxacin and 16% of CMC patients. It is concluded that i.v. to p.o. moxifloxacin is as effective as CMC for treatment of CAP and is a reliable alternative antimicrobial therapy.

Ciprofloxacin extended release: in the treatment of urinary tract infections and uncomplicated pyelonephritis.

Ciprofloxacin extended release (XR) is a new oral formulation of a fluoroquinolone that allows once-daily administration while maintaining therapeutic serum levels of the drug. The maximum plasma concentrations (Cmax) of once-daily ciprofloxacin XR 500 mg was higher than that of twice-daily ciprofloxacin immediate release 250 mg and the Cmax of once-daily ciproflocaxin XR 1000 mg was higher than that of twice-daily ciprofloxacin 500 mg. No accumulation of ciprofloxacin XR at steady state was observed in healthy men and all other pharmacokinetic parameters were similar to those of the immediate-release formulation. In patients with uncomplicated urinary tract infection (UTI), bacteriological eradication rates were similar in recipients of ciprofloxacin XR and immediate-release ciprofloxacin at the test-of-cure (TOC) visit, as were rates of persistence or new infection. Clinical cure rates were also similar in the two treatment groups. Bacteriological eradication occurred in 89% of ciprofloxacin XR and 85% of immediate-release ciprofloxacin recipients with complicated UTIs or acute uncomplicated pyelonephritis at the TOC visit. Clinical cure rates were also similar in the two treatment groups. black triangle Ciprofloxacin XR was generally well tolerated in patients with uncomplicated or complicated UTIs or acute uncomplicated pyelonephritis and showed similar tolerability to that of the immediate-release formulation.

Efficacy and Tolerability of Telithromycin for 5 or 10 Days vs Amoxicillin/Clavulanic Acid for 10 days in Acute Maxillary Sinusitis

Telithromycin (HMR 3647) is a new ketolide antimicrobial that was developed for the treatment of community-acquired respiratory tract injections. We conducted a randomized, double-blind, multicenter study to compare the clinical efficacy and safety of oral telithromycin, at 800 mg once daily for 5 or 10 days, with that of amoxicillin/clavulanic acid, at 500/125 mg three times daily for 10 days, in adults with acute maxillary sinusitis (AMS). A total of 754 patients with AMS of less than 28 days' duration were randomized to receive either telithromycin for 5 days followed by placebo for 5 days, telithromycin for 10 days, or amoxicillin/clavulanic acid for 10 days. Clinical outcome was assessed at a test-of-cure (TOC) visit between days 17 and 24 and at a late post-therapy visit between days 31 and 45. Analysis of clinical outcome on a per-protocol basis (n = 434) demonstrated therapeutic equivalence among the three regimens at the TOC visit; in each treatment group, the clinical cure rate was approximately 75%. Only a few patients (3 to 5 in each group) had relapsed by the late post-therapy follow-up visit. Telithromycin was generally safe and well tolerated. The most common adverse events were mild or moderate gastrointestinal effects, which occurred with similar frequency in all three groups. We conclude that 5 or 10 days of telithromycin at 800 mg once daily is as effective clinically and as well tolerated as 10 days of treatment with amoxicillin/clavulanic acid. Telithromycin, therefore, appears to be a valuable option for the treatment of AMS.

PID5: MOXIFLOXACIN VS AMOXICILLIN/CLAVULANATE IN THE TREATMENT OF ACUTE MAXILLARY SINUSITIS (AMS): EFFICACY, SAFETY AND PATIENT-REPORTED OUTCOMES IN PRIMARY CARE

OBJECTIVE: This study was designed to reflect real-world experience in the treatment of patients with AMS. Efficacy, safety, and patient-reported outcomes variables were compared between moxifloxacin (MXF) and amoxicillin/clavulanate (AC) for the management of AMS in a primary care setting. METHODS: In this prospective, multicenter, non-blinded phase IIIb trial, 475 adult patients with symptoms of AMS were randomized to receive a 10-day oral regimen of either MXF (400mg once-daily) or AC (875mg twice-daily). Clinical success at the test-of-cure (TOC) visit (post-therapy days 14–21) was the primary efficacy measure. Secondary outcomes included rate of clinical relapse at follow-up (post-therapy days 26–46) and exploratory evaluation of patient-reported outcomes variables. Safety data was also tabulated from intent-to-treat (ITT) patients. RESULTS: Of 471 adults comprising the ITT population (234 MXF, 237 AC), MXF treatment was statistically equivalent to AC at the TOC visit (85.2% vs 81.8%; 95%CI = −6%,13%). Per-protocol analysis also confirmed statistical equivalence between MXF and AC (86.5% vs 83.6%; 95%CI = −7%,13%). Rates of relapse were similar for the ITT (4% MXF, 5% AC) and the per-protocol (4% both) populations. The frequency of drug-related adverse events were similar between MXF (30%) and AC (25%) and were primarily gastrointestinal-related: nausea (11% MXF, 5% AC) and diarrhea (3% MXF, 10% AC). At the TOC visit, significantly more MXF-treated patients (n = 47; 24%) in the ITT population than AC-treated patients (n = 28; 14%) reported symptomatic improvement by day 3 (p < 0.02). No differences existed in terms of lost work hours or time to return to normal activities between treatment groups. CONCLUSIONS: In this primary care clinical trial, once-daily MXF was as effective and safe as twice-daily AC in the treatment of AMS. In some patients, MXF was associated with more rapid symptomatic relief, which has potential clinical and socioeconomic implications.

The value of tests of cure following cervical chlamydial infection.

Test of cure (TOC) was performed 2, 4 and 6 weeks after treatment for cervical chlamydia infection with 10-14 days of Deteclo one tablet twice daily, erythromycin 500 mg twice daily or doxycycline 100 mg twice daily. Testing was by chlamydia culture and IDEIA (DAKO diagnostics Ltd). Discrepant results were subsequently checked by immunofluorescence (Syva MicroTrak) of both sets of left over transport media. Two hundred and three patients attended on at least one occasion; 189, 146 and 107 at 2, 4 and 6 weeks respectively. Of these 127, 70 and 34, respectively, denied sexual intercourse or had consistently used condoms. Fourteen were positive over the study period by either or both methods of detection. Of 8 culture positive results 3 were negative by IDEIA. Two of these had elementary bodies (EBs) on immunofluorescence of both sets of saved transport media. One had EBs on immunofluorescence of the saved culture transport medium only. None of the 6 IDEIA positive, culture negative patients had immunofluorescent EBs in the IDEIA transport media although one had EBs in the saved culture transport medium. One IDEIA suspicious, culture negative patient had EBs in both sets of saved transport media. There was no significant difference in the rate of chlamydia detection from patients admitting to or denying unprotected intercourse. TOC has a low yield in cases of cervical chlamydial infection when there has been careful contact tracing and treatment has been completed. If TOC is performed culture should be used if available and where antigen detection methods are used confirmation should be sought for any positive results.

Survey of the management of Chlamydia trachomatis infection of the cervix.

A questionnaire was sent to all genitourinary medicine (GUM) clinics in the United Kingdom. Physicians were asked whether women attending the clinics were routinely screened for Chlamydia trachomatis, what treatment was given and whether and how a test of cure (TOC) was carried out after treatment; 94.5% of clinics responded. Screening for chlamydia was not carried out routinely in 4.8% of clinics. Treatments and their costs varied widely between clinics; six antibiotics were prescribed in 35 different ways. Less than half the clinics used regimens compatible with the advice of the World Health Organisation (WHO) and the Centers for Disease Control (CDC). Antibiotics in larger doses and/or for longer durations than those known to be effective were prescribed in 85% of clinics. Unnecessary routine TOC were carried out by 86% of clinics in 29 different ways. Sixteen percent of clinics carried out TOC immediately after completion of therapy, which is inadvisable on technical grounds. There is a need to standardise and improve the treatment and follow-up of chlamydial infection in women attending GUM clinics.

Test of cure for gonorrhea in teenagers: Who complies and does continuity of care help?

This study evaluates factors influencing test of cure (TOC) compliance for gonorrhea in teenagers attending a public sexually transmitted disease (STD) clinic. The efficacy of providing continuity of care to improve the TOC rate is also evaluated. Overall, females complied better (54%) than males (33%), and younger males better than older males (>16 years of age). Of patients with a prior history of gonorrhea, the TOC rates were significantly higher for those who had previously kept their TOC appointment. Continuity of care did not improve the TOC rate, but initial contact with a clinician appeared to influence the return rate of female adolescents. Male adolescents will apparently require a different intervention strategy to improve their appointment keeping.

STUDIES ON NEISSERIA GONORRHOEAE STRAINS FROM TEST‐OF‐CURE SPECIMENS

Sixty-seven out of 88 Neisseria gonorrhoeae strains isolated from test-of-cure (TOC) specimens during a five-months' period were included in the study. For 62 patients sufficient information was obtained in order to distinguish between relapse (34 ptt) and re-infection (28 ptt). For comparison with strains from these two groups of patients, 63 urogenital and 21 pharyngeal gonococcal strains isolated during the same period of time were randomly selected. The distributions according to susceptibility to penicillin for TOC strains and control strains corresponded to those found for the total number of TOC strains (275) and other strains (3,345) tested in 1979, respectively. The TOC strains did not differ from the control strains in sensitivity to the complement-dependent. The TOC strains did not differ from the control strains in sensitivity to the complement-dependent bactericidal activity of normal human serum. However, gonococcal strains less susceptible to penicillin in vitro (MIC values within the range 0.1-2.0 microgram/ml) were significantly more sensitive to the complement-dependent activity of normal human serum (P less than 0.01) than strains fully susceptible to penicillin (MIC less than 0.01 microgram/ml.) Penicillin-resistant strains (MIC greater than 2.0 microgram/ml) did not differ from strains susceptible to less than 0.1 microgram penicillin/ml and were slightly more serum-resistant than the less susceptible strains (P less than 0.05). No difference in serum-sensitivity of urogenital and pharyngeal isolates could be demonstrated. The level of bactericidal activity of homologous convalescent serum was unrelated to the presence of antibodies either to gonococcal pili or crude gonococcal antigen preparations. The sensitivity to normal human serum of a certain strain was not correlated with sensitivity to homologous convalescent serum.