Levofloxacin based non-rifampicin anti-tuberculous therapy: An effective alternative in renal transplant recipients in resource limited setting.

INTRODUCTION: Rifampicin is one of the most effective components of anti-tuberculous therapy (ATT). Since rifampicin is a hepatic enzyme (CYP3A4) inducer, in a post-renal transplant recipient, the dose of calcineurin inhibitors needs to be up-regulated and frequently monitored. In resource-limited (low- and lower-middle-income countries) setting this is not always feasible. Therefore, we evaluated a non-rifampicin-based ATT using levofloxacin in kidney transplant recipients. METHODS: We retrospectively studied the medical records of renal transplant recipients diagnosed with tuberculosis in our institute between 2014 and 2017. After a brief discussion with patients regarding the nature and course of ATT, those who opted for a non-rifampicin based therapy due to financial constraints were included in the study and followed for a minimum of 6 months period after the completion of ATT. RESULTS: Out of the 550 renal transplant recipients, 67 (12.2%) developed tuberculosis after a median period of 24 (1-228) months following transplantation, of them, 64 patients opted for non-rifampicin-based ATT. The mean age was 37.6 years. Only 25% were given anti-thymocyte globulin based induction, while the majority (56; 87.5%) of them were on tacrolimus-based triple-drug maintenance therapy. Extrapulmonary tuberculosis was noted in 33% of cases, while 12 (18.7%) had disseminated disease. The median duration of treatment was 12 months and the cure rate of 93.7% (n = 60) was achieved at the end of therapy. CONCLUSION: Levofloxacin based ATT appears to be a safe and effective alternative of rifampicin in kidney transplant recipients who cannot afford heightened tacrolimus dosage.

Levofloxacin prophylaxis in hospitalized children with leukemia: A cost-utility analysis.

BACKGROUND: Infections are common and are a major cause of morbidity and mortality during treatment of childhood leukemia. We evaluated the cost effectiveness of levofloxacin antibiotic prophylaxis, compared to no prophylaxis, in children receiving chemotherapy for acute myeloid leukemia (AML) or relapsed acute lymphoblastic leukemia (ALL). PROCEDURES: A cost-utility analysis was conducted from the perspective of the single-payer health care system using a lifetime horizon. A comprehensive literature review identified available evidence for effectiveness, safety, costs of antibiotic prophylaxis in children with leukemia, and health utilities associated with the relevant health states. The effects of levofloxacin prophylaxis on health outcomes, quality-adjusted life-years (QALY), and direct health costs were derived from a combined decision tree and state-transition model. One-way deterministic and probabilistic sensitivity analyses were performed to test the sensitivity of results to parameter uncertainty. RESULTS: The literature review revealed one randomized controlled trial on levofloxacin prophylaxis in childhood AML and relapsed ALL, by Alexander et al, that showed a significant reduction in rates of fever and neutropenia (71.2% vs 82.1%) and bacteremia (21.9% vs 43.4%) with levofloxacin compared to no prophylaxis. In our cost-utility analysis, levofloxacin prophylaxis was dominant over no prophylaxis, resulting in cost savings of $542.44 and increased survival of 0.13 QALY. In probabilistic sensitivity analysis, levofloxacin prophylaxis was dominant in 98.8% of iterations. CONCLUSIONS: The present analysis suggests that levofloxacin prophylaxis, compared to no prophylaxis, is cost saving in children receiving intensive chemotherapy for AML or relapsed ALL.

Cost-effectiveness of levofloxacin prophylaxis against bacterial infection in pediatric patients with acute myeloid leukemia.

BACKGROUND: Infections are the leading cause of therapy-related mortality in pediatric patients with acute myeloid leukemia (AML). Although effectiveness of levofloxacin antibacterial prophylaxis in oncology patients is recognized, its cost-effectiveness is unknown. This study evaluated epidemiologic data regarding levofloxacin use and the cost-effectiveness of this strategy as the cost per bacteremia episode, intensive care unit (ICU) admission, and death avoided in children with AML. PROCEDURE: A retrospective cohort study using the Pediatric Health Information System (PHIS) database compared demographic and clinical characteristics and receipt of levofloxacin prophylaxis in children with AML admitted for chemotherapy from January 1, 2014, through December 31, 2018. We then developed a decision analysis model in this population that compared costs associated with bacteremia, ICU admission, or death secondary to bacteremia to levofloxacin prophylaxis cost from a healthcare perspective. Time horizon is one chemotherapy cycle. Probabilistic and one-way sensitivity analyses evaluated model uncertainty. RESULTS: Prophylaxis cost $8491 per bacteremia episode prevented compared with an average added hospital cost of $119 478. Prophylaxis cost $81 609 per ICU admission avoided, compared with an average added hospital cost of $94 181. Prophylaxis cost $220 457 per death avoided. In sensitivity analysis, at a willingness-to-pay threshold of $100 000 per bacteremia episode avoided, prophylaxis remained cost-effective in 94.6% of simulations. Prophylaxis use was more common in recent years in patients with relapsed disease and with chemotherapy regimens considered more intensive. CONCLUSION: Prophylaxis is cost-effective in preventing bacterial infections in patients with AML. Findings support increased use in patients considered at high risk of bacterial infection secondary to myelosuppression.

Cost analysis of antibiotic therapy versus appendectomy for treatment of uncomplicated acute appendicitis: 5-year results of the APPAC randomized clinical trial.

BACKGROUND: The efficacy and safety of antibiotic treatment for uncomplicated acute appendicitis has been established at long-term follow-up with the majority of recurrences shown to occur within the first year. Overall costs of antibiotics are significantly lower compared with appendectomy at short-term follow-up, but long-term durability of these cost savings is unclear. The study objective was to compare the long-term overall costs of antibiotic therapy versus appendectomy in the treatment of uncomplicated acute appendicitis in the APPAC (APPendicitis ACuta) trial at 5 years. METHODS AND FINDINGS: This multicentre, non-inferiority randomized clinical trial randomly assigned 530 adult patients with CT-confirmed uncomplicated acute appendicitis to appendectomy or antibiotic treatment at six Finnish hospitals. All major costs during the 5-year follow-up were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis. Between November 2009 and June 2012, 273 patients were randomized to appendectomy and 257 to antibiotics. The overall costs of appendectomy were 1.4 times higher (p<0.001) (€5716; 95% CI: €5510 to €5925) compared with antibiotic therapy (€4171; 95% CI: €3879 to €4463) resulting in cost savings of €1545 per patient (95% CI: €1193 to €1899; p<0.001) in the antibiotic group. At 5 years, the majority (61%, n = 156) of antibiotic group patients did not undergo appendectomy. CONCLUSIONS: At 5-year follow-up antibiotic treatment resulted in significantly lower overall costs compared with appendectomy. As the majority of appendicitis recurrences occur within the first year after the initial antibiotic treatment, these results suggest that treating uncomplicated acute appendicitis with antibiotics instead of appendectomy results in lower overall costs even at longer-term follow-up.

Levofloxacin versus placebo for the prevention of tuberculosis disease in child contacts of multidrug-resistant tuberculosis: study protocol for a phase III cluster randomised controlled trial (TB-CHAMP).

BACKGROUND: Multidrug-resistant (MDR) tuberculosis (TB) presents a challenge for global TB control. Treating individuals with MDR-TB infection to prevent progression to disease could be an effective public health strategy. Young children are at high risk of developing TB disease following infection and are commonly infected by an adult in their household. Identifying young children with household exposure to MDR-TB and providing them with MDR-TB preventive therapy could reduce the risk of disease progression. To date, no trials of MDR-TB preventive therapy have been completed and World Health Organization guidelines suggest close observation with no active treatment. METHODS: The tuberculosis child multidrug-resistant preventive therapy (TB-CHAMP) trial is a phase III cluster randomised placebo-controlled trial to assess the efficacy of levofloxacin in young child contacts of MDR-TB cases. The trial is taking place at three sites in South Africa where adults with MDR-TB are identified. If a child aged < 5 years lives in their household, we assess the adult index case, screen all household members for TB disease and evaluate any child aged < 5 years for trial eligibility. Eligible children are randomised by household to receive daily levofloxacin (15-20 mg/kg) or matching placebo for six months. Children are closely monitored for disease development, drug tolerability and adverse events. The primary endpoint is incident TB disease or TB death by one year after recruitment. We will enrol 1556 children from approximately 778 households with an average of two eligible children per household. Recruitment will run for 18-24 months with all children followed for 18 months after treatment. Qualitative and health economic evaluations are embedded in the trial. DISCUSSION: If the TB-CHAMP trial demonstrates that levofloxacin is effective in preventing TB disease in young children who have been exposed to MDR-TB and that it is safe, well tolerated, acceptable and cost-effective, we would expect that that this intervention would rapidly transfer into policy. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN92634082 . Registered on 31 March 2016.

Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial.

BACKGROUND: An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis. The objective of this study was to compare the costs of antibiotics alone versus appendicectomy in treating uncomplicated acute appendicitis within the randomized controlled APPAC (APPendicitis ACuta) trial. METHODS: The APPAC multicentre, non-inferiority RCT was conducted on patients with CT-confirmed uncomplicated acute appendicitis. Patients were assigned randomly to appendicectomy or antibiotic treatment. All costs were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis during the 1-year follow-up. The cost estimates were based on cost levels for the year 2012. RESULTS: Some 273 patients were assigned to the appendicectomy group and 257 to antibiotic treatment. Most patients randomized to antibiotic treatment did not require appendicectomy during the 1-year follow-up. In the operative group, overall societal costs (€5989·2, 95 per cent c.i. 5787·3 to 6191·1) were 1·6 times higher (€2244·8, 1940·5 to 2549·1) than those in the antibiotic group (€3744·4, 3514·6 to 3974·2). In both groups, productivity losses represented a slightly higher proportion of overall societal costs than all treatment costs together, with diagnostics and medicines having a minor role. Those in the operative group were prescribed significantly more sick leave than those in the antibiotic group (mean(s.d.) 17·0(8·3) (95 per cent c.i. 16·0 to 18·0) versus 9·2(6·9) (8·3 to 10·0) days respectively; P < 0·001). When the age and sex of the patient as well as the hospital were controlled for simultaneously, the operative treatment generated significantly more costs in all models. CONCLUSION: Patients receiving antibiotic therapy for uncomplicated appendicitis incurred lower costs than those who had surgery.

Cost-effectiveness analysis of oral versus intravenous drip infusion of levofloxacin in the treatment of acute lower respiratory tract infection in Chinese elderly patients.

AIM: Pharmacoeconomic cost-effectiveness analysis of two different dosage regimens of levofloxacin in the treatment of acute lower respiratory tract infection in elderly patients. METHODS: A total of 108 elderly patients with acute lower respiratory tract infection who visited by our hospital between September 2013 and September 2014 were randomly divided into Group A and Group B, with 54 patients in each group. In Group A, levofloxacin injection was given for continuous intravenous infusion treatment, whereas in Group B, levofloxacin injection and levofloxacin capsule were given as sequential therapy (ST). The period of treatment for both the groups was 10 days, and minimum cost analysis was used to analyze the treatment. RESULTS: Groups A and B had cure rates of 61.1% and 59.3% (P>0.05), effective rates of 88.9% and 83.3% (P>0.05), bacterial clearance rates of 96.3% and 92.6% (P>0.05), and incidence rates of adverse reactions of 7.4% and 3.7% (P>0.05), respectively. Treatment costs of Groups A and B were 1,588 RMB and 1,150 RMB, respectively, whereas the cost-effectiveness of the two groups was at 17.86 and 13.81, respectively (P<0.05). CONCLUSION: Levofloxacin ST had relatively higher cost-effectiveness ratio for the treatment of acute lower respiratory tract infection in elderly patients, especially Chinese.

Comparison of the effectiveness and antibiotic cost among ceftriaxone, ertapenem, and levofloxacin in treatment of community-acquired complicated urinary tract infections.

PURPOSE: To study characteristics of patients with community-acquired complicated urinary tract infections (cUTIs) and to compare effectiveness and antibiotic cost of treatment with ceftriaxone (CRO), levofloxacin (LVX), and ertapenem (ETP). METHODS: This retrospective study enrolled patients who had community-acquired cUTIs admitted to Division of Infectious Diseases in a single medical center from January 2011 to March 2013. Effectiveness, antibiotic cost, and clinical characteristics were compared among patients treated with CRO, LVX, and ETP. RESULTS: There were 358 eligible cases, including 139 who received CRO, 128 treated with ETP, and 91 with LVX. The most common pathogen was Escherichia coli. The susceptibilities of these three agents were higher and more superior than first-line antibiotics. Treatment with ETP was associated with a significantly shorter time to defervescence since admission (CRO: 39 hours, ETP: 30 hours, and LVX: 38 h; p = 0.031) and shorter hospitalization stay (CRO: 4 days, ETP: 3 days, and LVX: 4 days; p < 0.001). However, the average antibiotic costs in the CRO group were significantly lower than that in the other two groups [CRO: 62.4 United States dollars (USD), ETP: 185.33 USD, and LVX: 204.85 USD; p < 0.001]. CONCLUSION: The resistance of cUTIs isolates to first-line antibiotic is high. Using ETP, CRO, and LVX in the treatment of cUTIs for good clinical response should be suggested. Among the three agents, ETP had better susceptibility than CRO and LVX, reached defervescence sooner, and was associated with shorter hospital stays. However, using CRO in cUTIs was less expensive than the other two agents.

Prophylactic use of levofloxacin during medicinal leech therapy.

BACKGROUND: Medicinal leech therapy is effective in establishing venous outflow in congested flaps and replants. However, its use is also associated with infections, especially from Aeromonas species. To prevent this nosocomial infection, levofloxacin has been established as prophylaxis during leech therapy in our hospital. OBJECTIVES: To study the implementation rate of a guideline, to study the effect of levofloxacin on possible Aeromonas infections, and to evaluate the financial impact of this preventive measure. SETTING: A retrospective analysis on all patients treated with Hirudo medicinalis between July 2007 and March 2011 was performed at the Ghent University Hospital, Belgium. METHOD: A list of patients treated with leeches was retrieved from the pharmacy database. Patient characteristics, date of start and stop of leech therapy were collected. Data on routine diagnostic cultures during leech therapy, date and type of clinical sample, while cultivated micro-organism with antibiotic susceptibility were obtained from the laboratory database. MAIN OUTCOME MEASURE: percentage implementation rate of a guideline, presence of Aeromonas infections, financial impact of levofloxacin prophylaxis. RESULTS: Fifty-one patients were treated with leeches. Forty-six (90.2 %) patients were treated according the guideline. Fourteen out of 51 patients (27.5 %) were suspected for postoperative wound infections. From them, 60 clinical samples were sent for microbiological analysis. These included exudates (26.7 %), peroperative samples (5.0 %), puncture fluid (1.7 %), blood cultures (3.3 %) or smears from burns (63.3 %). No Aeromonas species were cultivated. Comparison between period before and after implementation of levofloxacin prophylaxis revealed that levofloxacin prevents colonization or infection with Aeromonas species in relation to leech therapy. The direct cost for levofloxacin prophylaxis in the current study was 2,570 euro. Based on data obtained in a previous study, we presume that a minimum cost-saving of 20,500 euro was realised during the current study period by implementation of antimicrobial prophylaxis. CONCLUSIONS: This study demonstrates successful implementation of a guideline for levofloxacin prophylaxis during leech therapy. Following its introduction, no Aeromonas species related to the use of leeches were isolated as compared to 8.5 % in the baseline period.

Economic evaluation of adjustments of levofloxacin dosage by dispensing pharmacists for patients with renal dysfunction.

Since April 2011, a dosage adjustment program has been implemented at Gifu Municipal Hospital. In this program, upon receiving a prescription for renally eliminated drugs, pharmacists verify patients' serum creatinine concentrations by using a computerized medical record system to evaluate the patient's kidney function and suggest the appropriate dosage to doctors, if necessary. In our study, we used questionnaires that were administered to pharmacists and doctors at the hospital to investigate their respective working times and the cost of the program, in order to comprehensively analyze the clinical resource costs of the hospital and evaluate the economic burden of the program for levofloxacin. In addition, we studied the pharmacists' and doctors' attitudes toward the program and the circumstances of prescriptions for patients with renal dysfunction. The questionnaire comprised items such as time required for the program; attitude toward the program, including satisfaction; and attitude toward the circumstances of prescriptions for patients with renal dysfunction. The pharmacists' and doctors' working times and cost of the program were obtained from the questionnaire responses. For cost estimation, we used data from this study as well as those of our previous study that suggested that the levofloxacin program was economically beneficial. Furthermore, their attitudes toward the program and circumstances of prescriptions for patients with renal dysfunction were clarified. Regarding the pharmacists' tasks and interventions, we need to not only investigate attitudes toward them but also perform a cost analysis by the method of the economic evaluation of the medical techniques used in our study.

[Antibiotic therapy regimens for mild community-acquired pneumonia in patients with risk factors for ineffective treatment: clinical and economic comparisons].

AIM: To evaluate the clinical efficiency, tolerance, and pharmacoeconomic parameters of treatment for mild community-acquired pneumonia (CAP) in patients with risk factors for ineffective treatment with levofloxacin (Glevo) versus original levofloxacin and standard pharmacotherapy regimens for mild pneumonia (real practice). SUBJECTS AND METHODS: An open-label comparative randomized trial was conducted in parallel groups of 147 patients aged > or = 18 years with mild CAP and risk factors for ineffective treatment. Group 1 included 61 patients (59 men and 2 women; mean age 23.3 +/- 11.2 years) receiving levofloxacin (Glevo) 500 mg/day; Group 2 comprised 41 patients (39 men and 1 woman; mean age 26.4 +/- 13.4 years) treated with original levofloxacin 500 mg/day; Group 3 consisted of 45 patients (all men; mean age 23.7 +/- 9.9 years) on standard therapy. The trial was performed in 3 pulmonology centers. RESULTS: The use of the respiratory fluoroquinolone levofloxacinto treat mild CAP in the patients with risk factors for failure for its therapy demonstrated a higher efficiency than the antibiotic regimens used in real clinical practice. This suggests that physicians underestimate risk factors and do not always make a rational choice of an antimicrobial agent in the given clinical situation. CONCLUSION: The generic form of levofloxacin (Glevo) is as clinically effective as its original drug in the treatment of CAP and characterized by its optimal pharmacoeconomic parameters.