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Abstract Rationale Levofloxacin (LFX) and moxifloxacin (MXF) are the two most frequently recommended fluoroquinolones for treatment of patients with multidrug-resistant tuberculosis (MDR-TB). However, studies comparing the effectiveness of LFX and MXF among patients with MDR-TB are lacking. Objectives To compare the effectiveness of LFX and MXF in terms of culture conversion after 3 months of treatment for MDR-TB. Methods In this prospective multicenter randomized open label trial, we randomly assigned 182 patients with MDR-TB (sensitive to LFX and MXF) to receive either LFX (750 mg/day; 90 patients) or MXF (400 mg/day; 92 patients) with a background drug regimen. The primary outcome was the proportion of patients who achieved sputum culture conversion at 3 months of treatment. Secondary outcomes were time to culture conversion and time to smear conversion, with data censored at 3 months, and the proportions of adverse drug reactions. Measurements and Main Results At 3 months of treatment, 68 (88.3%) of the 77 patients in the LFX group and 67 (90.5%) of the 74 in the MXF group showed conversion to negative sputum cultures (odds ratio for LFX compared with MXF, 0.78; 95% confidence interval, 0.27–2.20). Adverse drug reactions were reported in six patients (7.7%) in the LFX group and four (5.2%) in the MXF group (P = 0.75). Conclusions The choice of LFX or MXF for treatment of patients with MDR-TB may not affect sputum culture conversion at 3 months of treatment. Clinical trial registered with www.clinicaltrials.gov (NCT 01055145).

With the introduction of new anti-tuberculosis drugs, all-oral regimens with shorter treatment durations for multidrug-resistant tuberculosis have been anticipated. We aimed to investigate whether a new all-oral regimen was non-inferior to the conventional regimen including second-line anti-tuberculosis drugs for 20–24 months in the treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis. In this multicentre, randomised, open-label phase 2/3 non-inferiority trial, we enrolled men and women aged 19–85 years with multidrug-resistant tuberculosis confirmed by phenotypic or genotypic drug susceptibility tests or rifampicin-resistant tuberculosis by genotypic tests at 12 participating hospitals throughout South Korea. Participants with fluoroquinolone-resistant multidrug-resistant tuberculosis were excluded. Participants were randomly assigned (1:1) to two groups using a block randomisation, stratified by the presence of diabetes and cavitation on baseline chest radiographs. The investigational group received delamanid, linezolid, levofloxacin, and pyrazinamide for 9 months, and the control group received a conventional 20–24-month regimen, according to the 2014 WHO guidelines. The primary outcome was the treatment success rate at 24 months after treatment initiation in the modified intention-to-treat population and the per-protocol population. Participants who were “cured” and “treatment completed” were defined as treatment success following the 2014 WHO guidelines. Non-inferiority was confirmed if the lower limit of a 97·5% one-sided CI of the difference between the groups was greater than −10%. Safety data were collected for 24 months in participants who received a predefined regimen at least once. This study is registered with ClinicalTrials.gov, NCT02619994. Between March 4, 2016, and Sept 14, 2019, 214 participants were enrolled, 168 (78·5%) of whom were included in the modified intention-to-treat population. At 24 months after treatment initiation, 60 (70·6%) of 85 participants in the control group had treatment success, as did 54 (75·0%) of 72 participants in the shorter-regimen group (between-group difference 4·4% [97·5% one-sided CI –9·5% to ∞]), satisfying the predefined non-inferiority margin. No difference in safety outcomes was identified between the control group and the shorter-regimen group. 9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis. Korea Disease Control and Prevention Agency, South Korea

Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma. TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35. Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8–13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51–0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group. Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy. UK National Institute for Health Research.

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 We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. Methods This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. Results Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI − 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). Conclusions The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

Vonoprazan, a novel and potent acid suppressant, has recently been incorporated into Helicobacter pylori eradication regimens. However, the data on combination of vonoprazan with levofloxacin remains scarce. This study represents one of the first evaluations comparing 7-day and 14-day once-daily regimens containing vonoprazan, levofloxacin, clarithromycin-MR, and bismuth for H. pylori eradication in regions characterized by high clarithromycin and metronidazole resistance. Between March 2022 and December 2023, patients presenting with dyspepsia who underwent upper gastrointestinal endoscopy at a tertiary care hospital in Thailand were recruited. Those testing positive for H. pylori infection were randomly assigned to receive either a 7-day or 14-day once-daily regimen comprising vonoprazan 40 mg, clarithromycin-MR 1 g, levofloxacin 500 mg, and bismuth subsalicylate 1,048 mg. CYP3A4 polymorphism testing and antimicrobial susceptibility assessment (using either the Epsilometer test or the GenoType ® HelicoDR assay) were performed. Eradication was confirmed by a negative ¹³C-urea breath test conducted no sooner than four weeks after completing therapy. A total of 312 dyspeptic patients who underwent EGD were screened, and 102 (32.7%) were diagnosed with H. pylori infection. The study enrolled and randomized these patients into two treatment groups: 51 received the 7-day once-daily vonoprazan-based bismuth therapy, and 51 received the 14-day regimen. Baseline characteristics were similar between the two groups, except for a higher prevalence of hypertension in the 7-day regimen group (49% vs. 27.5%, p  = 0.025). The eradication rates for the 7-day regimen were 88.2% (45/51) in the intention-to-treat (ITT) analysis and 89.6% (43/48) in the per-protocol (PP) analysis. Similarly, the 14-day regimen achieved eradication rates of 88.2% (45/51) in the ITT analysis and 93.8% (45/48) in the PP analysis. The risk difference for eradication in the PP analysis was 4.17% (95% CI: -6.86 to 15.19, p  = 0.71). Adverse events were comparable between the two regimens, occurring in 35.3% (18/51) of patients in the 7-day regimen and 38.8% (19/51) in the 14-day regimen ( p  = 0.130). The most frequently reported adverse event was black stool (35.3% vs. 38.8%, p  = 0.130). Other adverse events included nausea and vomiting (15.7% vs. 22.5%, p  = 0.742), bitter taste (17.7% vs. 18.4%, p  = 1.000), and dizziness (7.8% vs. 6.1%, p  = 0.113). All adverse events resolved spontaneously without requiring medical intervention, and no serious adverse events were reported. The 14-day regimen demonstrated excellent eradication rate (> 90%) regardless of CYP3A4 polymorphisms. These findings suggest that vonoprazan, levofloxacin, clarithromycin-MR, and bismuth for 14 days is a promising alternative first-line treatment option, particularly in regions with high clarithromycin and metronidazole resistance.

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.

Due to the different effects of various drugs and the lack of authoritative and unified guidelines in clinical practice, the choice of therapeutic drugs for pulmonary tuberculosis (TB) remains controversial. Rifampicin, levofloxacin, and isoniazid are all anti-TB drugs. However, no comparative studies of the treatment effects of rifampicin + levofloxacin and rifampicin + isoniazid have occurred. The study intended to analyze the therapeutic effects of rifampicin + levofloxacin compared to rifampicin + isoniazid in the treatment of pulmonary TB to provide a clinical reference, which could provide new references for future clinical treatment of the disease. The research team conducted a prospective controlled study. The study took place at Zibo Zhoucun District People's Hospital in Zibo, China. Participants were 100 patients with pulmonary TB admitted to the hospital between March 2021 and December 2022. The research team assigned participants to one of two groups: (1) the intervention group, with 56 participants who received rifampicin + levofloxacin therapy, and (2) the control group, with 44 participants who received rifampicin + isoniazid. The research team measured: (1) clinical efficacy, (2) incidence of adverse reactions, (3) changes in inflammatory factors, (4) changes in immunoglobulins (Igs), and (5) changes in T lymphocyte subsets. The intervention group's total effective rate for treatment was significantly higher than that of the control group (P = .049). However, no significant difference existed between the groups in the incidence of adverse reactions (P > .05). Postintervention, the intervention group's inflammatory factors-IL-6, TNF-α, hs-CRP, and β-EP-were significantly lower and its immunoglobulins (Igs) G/A/M (IgG/A/M) were significantly higher than those of the control group (P < .05). In addition, the intervention group's T lymphocyte subpopulations of CD3+ and CD4+ and CD4+/CD8+ were significantly higher and CD8+ was significantly lower than those in the control group (P < .05). In other words, the intervention group had a better immune function. Compared with rifampicin + isoniazid, rifampicin + levofloxacin had a better clinical effect in the treatment of pulmonary TB and could effectively regulate patients' immune functions and inhibit inflammatory reactions. The current research team recommends that rifampicin + levofloxacin become the preferred treatment for pulmonary TB in the absence of a drug allergy.

Background Helicobacter pylori ( H. pylori ) is affecting half of the globe. It is considered a main causative organism of chronic gastritis, peptic ulcer disease, and different gastric maliganacies. It has been also correlated to extraintestinal diseases, including refractory iron deficiency anaemia, vitamin B12 deficiency, and immune thrombocytopenic purpura. The misuse of antibiotics during the coronavirus diseases 2019 (COVID-19) pandemic time can affect H. pylori eradication rates. Our aim was to compare the efficacy of clarithromycin versus levofloxacin-based regimens for H. pylori treatment in naïve patients after the COVID-19 pandemic misuse of antibiotics. Methods A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were recruited. Patients were randomized to receive either clarithromycin, esomeprazole, and amoxicillin, or levofloxacin, esomeprazole, and amoxicillin. Results A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were included, 135 in each arm. In total, 19 patients in the clarithromycin group and 18 patients in the levofloxacin group stopped treatment after 2–4 days because of side effects or were lost for follow-up. Finally, 116 subjects in the clarithromycin group and 117 in the levofloxacin group were assessed. The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: group I, 55.56% and 64.66%; and Group II, 64.44% and 74.36% respectively (p = 0.11). Conclusion As COVID-19 pandemic has moved forward fast, high resistance rates of H. pylori to both clarithromycin and levofloxacin were developed after less than two years from the start of the pandemic. Molecular & genetic testing is highly recommended to identify antimicrobial resistance patterns. Strategies to prevent antibiotic misuse in the treatment of COVID-19 are needed to prevent more antibiotic resistance. Trial Registration : The trial was registered on Clinicaltrials.gov NCT05035186. Date of registration is 2-09-2021.

Fosfomycin, approved in the United States only for cystitis, is an attractive alternative for oral treatment of outpatient complicated urinary tract infections (cUTIs) as it has antimicrobial activity against most common uropathogens. The study was a multicenter, randomized, open-label pragmatic superiority clinical trial evaluating the efficacy of oral fosfomycin versus oral levofloxacin strategies in cUTIs (FOCUS study). The trial compared two strategies for initial or step-down oral therapy of cUTI without bacteremia after 0–48 hours of parenteral antibiotic therapy. Subjects were assigned to 3 g of fosfomycin or 750 mg (or dose adjusted for kidney function) of levofloxacin daily for 5–7 days. Clinical and microbiological cures were assessed at the end of therapy (EOT) and test of cure (TOC) (approximately 21 days from the start of antibiotics). The trial did not meet accrual goals; thus, the results were descriptive. Only 51 subjects were included in the microbiological intention-to-treat population. The subjects were mainly females (76%), with a mean age of 46.7 years (standard deviation [SD] = 20.8) and acute pyelonephritis (88%). At the end of therapy, clinical cure remained similar (69% and 68% for fosfomycin and levofloxacin strategies, respectively), and microbiological success was 100% for both strategies. At the test of cure, clinical cure was similar (84% and 86% in the fosfomycin and levofloxacin strategies, respectively); however, a numerically lower microbiological success was observed for fosfomycin (69% compared to 84% for levofloxacin). These limited data suggest that fosfomycin could be an oral alternative as a step-down therapy for the treatment of cUTIs (registry number NCT 03697993). Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics.