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We previously showed that the choice of levofloxacin or moxifloxacin for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-TB) did not affect sputum culture conversion at 3 months of treatment. To compare final treatment outcomes between patients with MDR-TB randomized to levofloxacin or moxifloxacin. A total of 151 participants with MDR-TB who were included for the final analysis in our previous trial were followed through the end of treatment. Treatment outcomes were compared between 77 patients in the levofloxacin group and 74 in the moxifloxacin group, based on the 2008 World Health Organization definitions as well as 2013 revised definitions of treatment outcomes. In addition, the time to culture conversion was compared between the two groups. Treatment outcomes were not different between the two groups, based on 2008 World Health Organization definitions as well as 2013 definitions. With 2008 definitions, cure was achieved in 54 patients (70.1%) in the levofloxacin group and 54 (73.0%) in the moxifloxacin group (P = 0.72). Treatment success rates, including cure and treatment completed, were not different between the two groups (87.0 vs. 81.1%, P = 0.38). With 2013 definitions, cure rates (83.1 vs. 78.4%, P = 0.54) and treatment success rates (84.4 vs. 79.7%, P = 0.53) were also similar between the levofloxacin and moxifloxacin groups. Time to culture conversion was also not different between the two groups (27.0 vs. 45.0 d, P = 0.11 on liquid media; 17.0 vs. 42.0 d, P = 0.14 on solid media). Patients in the levofloxacin group had more adverse events than those in the moxifloxacin group (79.2 vs. 63.5%, P = 0.03), especially musculoskeletal ones (37.7 vs. 14.9%, P = 0.001). The choice of levofloxacin or moxifloxacin made no difference to the final treatment outcome among patients with fluoroquinolone-sensitive MDR-TB. Clinical trial registered with www.clinicalrials.gov (NCT01055145).

Tuberculous meningitis remains highly lethal. In this trial, an intensified regimen of levofloxacin and higher-dose rifampin added to standard therapy was compared with standard antituberculosis therapy alone. The intensified regimen did not result in a higher survival rate. Early treatment with antituberculosis chemotherapy and adjunctive treatment with glucocorticoids reduce the rate of death and disability from tuberculous meningitis, but the disease still kills or disables almost half the patients with the condition. 1 , 2 The current guidelines recommend treatment with four antituberculosis drugs for at least the first 2 months of therapy, followed by treatment with two drugs (rifampin and isoniazid) for an additional 7 to 10 months. 3 , 4 However, these recommendations are based on data from pulmonary tuberculosis and do not take into account the differential ability of antituberculosis drugs to penetrate the brain. Rifampin is considered to . . .

Prevention of drug-resistant tuberculosis is a global health priority. However, trials evaluating the effectiveness of treating infection among contacts of persons with drug-resistant tuberculosis are lacking. We conducted a double-blind, randomized, controlled trial comparing 6 months of daily levofloxacin (weight-based doses) with placebo to treat infection. The trial population comprised household contacts of persons with bacteriologically confirmed rifampicin-resistant or multidrug-resistant (MDR) tuberculosis in Vietnam. Contacts of any age with a positive tuberculin skin test or immunologic impairment were eligible. The primary end point was bacteriologically confirmed tuberculosis within 30 months. Secondary end points included grade 3 or 4 adverse events, death from any cause, and acquired drug resistance. Of 3948 persons screened for eligibility, 61 (1.5%) had coprevalent tuberculosis (defined as active tuberculosis disease diagnosed before randomization) and 2041 underwent randomization. Of these 2041 participants, 1995 (97.7%) completed 30 months of follow-up, had a primary end-point event, or died. Confirmed tuberculosis occurred in 6 participants (0.6%) in the levofloxacin group and 11 (1.1%) in the placebo group (incidence rate ratio, 0.55; 95% confidence interval [CI], 0.19 to 1.62); this difference was not significant. There was little difference in grade 3 or 4 adverse events between the two groups (risk difference, 1.0 percentage point; 95% CI, -0.3 to 2.4). Adverse events of any grade were reported in 306 participants (31.9%) taking levofloxacin and 125 (13.0%) taking placebo (risk difference, 18.9 percentage points; 95% CI, 14.2 to 23.6). No acquired fluoroquinolone resistance was observed. Although the incidence of tuberculosis was lower in the levofloxacin group than in the placebo group at 30 months, the difference was not significant. (Funded by the National Health and Medical Research Council of Australia; VQUIN MDR Australia New Zealand Clinical Trials Registry number, ACTRN12616000215426.).

Treatment of complicated urinary-tract infections is challenging due to rising antimicrobial resistance. We assessed the efficacy and safety of ceftolozane-tazobactam, a novel antibacterial with Gram-negative activity, in the treatment of patients with complicated lower-urinary-tract infections or pyelonephritis. ASPECT-cUTI was a randomised, double-blind, double-dummy, non-inferiority trial done in 209 centres in 25 countries. Between July, 2011, and September, 2013, hospital inpatients aged 18 years or older who had pyuria and a diagnosis of a complicated lower-urinary-tract infection or pyelonephritis were randomly assigned in a 1:1 ratio to receive intravenous 1·5 g ceftolozane-tazobactam every 8 h or intravenous high-dose (750 mg) levofloxacin once daily for 7 days. The randomisation schedule was computer generated in blocks of four and stratified by study site. The next allocation was obtained by the study site pharmacist via an interactive voice-response system. The primary endpoint was a composite of microbiological eradication and clinical cure 5–9 days after treatment in the microbiological modified intention-to-treat (MITT) population, with a non-inferiority margin of 10%. This study is registered with ClinicalTrials.gov, numbers NCT01345929 and NCT01345955. Of 1083 patients enrolled, 800 (73·9%), of whom 656 (82·0%) had pyelonephritis, were included in the microbiological MITT population. Ceftolozane-tazobactam was non-inferior to levofloxacin for composite cure (306 [76·9%] of 398 vs 275 [68·4%] of 402, 95% CI 2·3–14·6) and, as the lower bound of the two-sided 95% CI around the treatment difference was positive and greater than zero, superiority was indicated. Adverse event profiles were similar in the two treatment groups and were mainly non-serious. Treatment with ceftolozane-tazobactam led to better responses than high-dose levofloxacin in patients with complicated lower-urinary-tract infections or pyelonephritis. Cubist Pharmaceuticals.

In this randomized, controlled trial involving children with household exposure to multidrug-resistant tuberculosis, levofloxacin led to a lower incidence of tuberculosis than placebo, but the difference was not significant.

Commonly prescribed drugs called fluoroquinolones cause rare, disabling side effects. Researchers are struggling to work out why. Commonly prescribed drugs called fluoroquinolones cause rare, disabling side effects. Researchers are struggling to work out why.

To compare the safety of intracameral levofloxacin and intracameral cefazolin in patients undergoing cataract surgery. In this prospective, double-blind, randomized study, patients with senile cataracts who were undergoing phacoemulsification were assigned to receive intracameral levofloxacin (0.1 ml/0.5 mg; Cravit® 0.5%; Santen Pharmaceutical Ltd.) or intracameral cefazolin (0.1 ml/1 mg; generic). The endpoints were the occurrence of endophthalmitis during the 3-month follow-up period, best-corrected visual acuity (BCVA), the presence of anterior chamber (AC) inflammation with grading of AC cells and presence of flare, along with intraocular pressure (IOP), central corneal thickness (CCT), central foveal thickness (CFT), and cell density. A total of 50 patients (50 eyes) were enrolled, randomized, and completed the study. No cases of endophthalmitis were reported in either treatment group. There were no significant differences in BCVA, AC inflammation, IOP, CCT, CFT, or cell density between the groups at any timepoint. Importantly, no dose errors or serious adverse events were reported in either group. This study provides proof of concept that prophylactic intracameral levofloxacin (0.1 ml/0.5 mg) may have a comparable safety profile to intracameral cefazolin (0.1 ml/1 mg) in patients undergoing cataract surgery. Intracameral levofloxacin (0.1 ml/0.5 mg) may offer a viable alternative to cefazolin (0.1 ml/1 mg), particularly for patients with penicillin allergies, while also reducing the risk of dilution errors by eliminating the need for reconstitution. Larger, multicenter studies are warranted to confirm the efficacy of levofloxacin (0.1 ml/0.5 mg) in preventing endophthalmitis. NCT06710977, 02/12/2024, retrospectively registered.

Recommended treatment for travelers' diarrhea includes the combination of an antibiotic, usually a fluoroquinolone or azithromycin, and loperamide for rapid resolution of symptoms. However, adverse events, postdose nausea with high-dose azithromycin, effectiveness of single-dose rifaximin, and emerging resistance to front-line agents are evidence gaps underlying current recommendations. A randomized, double-blind trial was conducted in 4 countries (Afghanistan, Djibouti, Kenya, and Honduras) between September 2012 and July 2015. US and UK service members with acute watery diarrhea were randomized and received single-dose azithromycin (500 mg; 106 persons), levofloxacin (500 mg; 111 persons), or rifaximin (1650 mg; 107 persons), in combination with loperamide (labeled dosing). The efficacy outcomes included clinical cure at 24 hours and time to last unformed stool. Clinical cure at 24 hours occurred in 81.4%, 78.3%, and 74.8% of the levofloxacin, azithromycin, and rifaximin arms, respectively. Compared with levofloxacin, azithromycin was not inferior (P = .01). Noninferiority could not be shown with rifaximin (P = .07). At 48 and 72 hours, efficacy among regimens was equivalent (approximately 91% at 48 and 96% at 72 hours). The median time to last unformed stool did not differ between treatment arms (azithromycin, 3.8 hours; levofloxacin, 6.4 hours; rifaximin, 5.6 hours). Treatment failures were uncommon (3.8%, 4.4%, and 1.9% in azithromycin, levofloxacin, and rifaximin arms, respectively) (P = .55). There were no differences between treatment arms with postdose nausea, vomiting, or other adverse events. Single-dose azithromycin, levofloxacin, and rifaximin with loperamide were comparable for treatment of acute watery diarrhea. NCT01618591.

Background. Previous studies have demonstrated increased cardiovascular mortality related to azithromycin and levofloxacin. Risks associated with alternative drugs in the same class, including clarithromycin and moxifloxacin, were unknown. We used the Taiwan National Health Insurance Database to perform a nationwide, population-based study comparing the risks of ventricular arrhythmia and cardiovascular death among patients using these antibiotics. Methods. Between January 2001 and November 2011, a total of 10 684 100 patients were prescribed oral azithromycin, clarithromycin, moxifloxacin, levofloxacin, ciprofloxacin, or amoxicillin-clavulanate at outpatient visits. A logistic regression model adjusted for propensity score was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for adverse cardiac outcomes occurring within 7 days after the initiation of antibiotic treatment. Results. Compared with amoxicillin-clavulanate treatment, the use of azithromycin and moxifloxacin was associated with significant increases in the risks of ventricular arrhythmia and cardiovascular death. The adjusted ORs for ventricular arrhythmia were 4.32 (95% CI, 2.95–6.33) for azithromycin, 3.30 (95% CI, 2.07–5.25) for moxifloxacin, and 1.41 (95% CI, .91–2.18) for levofloxacin. For cardiovascular death, the adjusted ORs for azithromycin, moxifloxacin, and levofloxacin were 2.62 (95% CI, 1.69–4.06), 2.31 (95% CI, 1.39–3.84), and 1.77 (95% CI, 1.22–2.59), respectively. No association was noted between clarithromycin or ciprofloxacin and adverse cardiac outcomes. Conclusions. Healthcare professionals should consider the small but significant increased risk of ventricular arrhythmia and cardiovascular death when prescribing azithromycin and moxifloxacin. Additional research is needed to determine whether the increased risk of mortality is caused by the drugs or related to the severity of infection or the pathogens themselves.

Drug-resistant (DR) strains of Mycobacterium tuberculosis ( M . tb ) are increasingly recognised as a threat to global tuberculosis (TB) control efforts. Identifying people with DR-TB exposure/ infection and providing TB preventive therapy (TPT) is a public health priority. TB guidelines advise the evaluation of household contacts of newly diagnosed TB cases, with the provision of TPT to vulnerable populations, including young children (<5 years). Many children become infected with TB through exposure in their household. Levofloxacin is under evaluation as TPT in children exposed to M . tb strains with resistance to rifampicin and isoniazid (multidrug-resistant TB; MDR-TB). Prior to opening a phase 3 prevention trial in children <5 years exposed to MDR-TB, the pharmacokinetics and safety of a novel formulation of levofloxacin given daily was evaluated as part of a lead-in study. We conducted an exploratory qualitative study of 10 caregivers’ experiences of administering this formulation. We explored how the acceptability of levofloxacin as TPT is shaped by the broader impacts of MDR-TB on the overall psychological, social, and financial wellbeing of caregivers, many of whom also had experienced MDR-TB. Caregivers reported that the novel levofloxacin formulation was acceptable. However, caregivers described significant psychosocial challenges in the process of incorporating TPT administration to their children into their daily lives, including financial instability, withdrawal of social support and stigma. When caregivers themselves were sick, these challenges became even more acute. Although new child-friendly formulations can ameliorate some of the pragmatic challenges related to TPT preparation and administration, the overall psychosocial burden on caregivers responsible for administering TPT remains a major determinant of effective MDR-TB prevention in children.