Assessment of antibiotic prescribing pattern and cost for hospitalized patients: A study from Palestine.

BACKGROUND: One of the largest problems facing the world today is the morbidity and mortality caused by antibiotic resistance in bacterial infections. A major factor in antimicrobial resistance (AMR) is the irrational use of antibiotics. The objective of this study was to assess the prescribing pattern and cost of antibiotics in two major governmental hospitals in the West Bank of Palestine. METHODS: A retrospective cohort study was conducted on 428 inpatient prescriptions containing antibiotics from two major governmental hospitals, they were evaluated by some drug use indicators. The cost of antibiotics in these prescriptions was calculated based on the local cost. Descriptive statistics were performed using IBM-SPSS version 21. RESULTS: The mean ± SD number of drugs per prescription (NDPP) was 6.72 ± 4.37. Of these medicines, 38.9% were antibiotics. The mean ± SD number of antibiotics per prescription (NAPP) was 2.61 ± 1.54. The average ± SD cost per prescription (CPP) was 392 ± 744 USD. The average ± SD antibiotic cost per prescription (ACPP) was 276 ± 553 USD. The most commonly prescribed antibiotics were ceftriaxone (52.8%), metronidazole (24.8%), and vancomycin (21.0%). About 19% of the antibiotics were prescribed for intra-abdominal infections; followed by 16% used as prophylactics to prevent infections. Almost all antibiotics prescribed were administered intravenously (IV) 94.63%. In general, the average duration of antibiotic therapy was 7.33 ± 8.19 days. The study indicated that the number of antibiotics per prescription was statistically different between the hospitals (p = 0.022), and it was also affected by other variables like the diagnosis (p = 0.006), the duration of hospitalization (p < 0.001), and the NDPP (p < 0.001). The most commonly prescribed antibiotics and the cost of antibiotics per prescription were significantly different between the two hospitals (p < 0.001); The cost was much higher in the Palestinian Medical Complex. CONCLUSION: The practice of prescribing antibiotics in Palestine's public hospitals may be unnecessary and expensive. This has to be improved through education, adherence to recommendations, yearly immunization, and stewardship programs; intra-abdominal infections were the most commonly seen infection in inpatients and ceftriaxone was the most frequently administered antibiotic.

Antimicrobial resistance point-of-care testing for gonorrhoea treatment regimens: cost-effectiveness and impact on ceftriaxone use of five hypothetical strategies compared with standard care in England sexual health clinics.

BackgroundWidespread ceftriaxone antimicrobial resistance (AMR) threatens Neisseria gonorrhoeae (NG) treatment, with few alternatives available. AMR point-of-care tests (AMR POCT) may enable alternative treatments, including abandoned regimens, sparing ceftriaxone use. We assessed cost-effectiveness of five hypothetical AMR POCT strategies: A-C included a second antibiotic alongside ceftriaxone; and D and E consisted of a single antibiotic alternative, compared with standard care (SC: ceftriaxone and azithromycin).AimAssess costs and effectiveness of AMR POCT strategies that optimise NG treatment and reduce ceftriaxone use.MethodsThe five AMR POCT treatment strategies were compared using a decision tree model simulating 38,870 NG-diagnosed England sexual health clinic (SHC) attendees; A micro-costing approach, representing cost to the SHC (for 2015/16), was employed. Primary outcomes were: total costs; percentage of patients given optimal treatment (regimens curing NG, without AMR); percentage of patients given non-ceftriaxone optimal treatment; cost-effectiveness (cost per optimal treatment gained).ResultsAll strategies cost more than SC. Strategy B (azithromycin and ciprofloxacin (azithromycin preferred); dual therapy) avoided most suboptimal treatments (n = 48) but cost most to implement (GBP 4,093,844 (EUR 5,474,656)). Strategy D (azithromycin AMR POCT; monotherapy) was most cost-effective for both cost per optimal treatments gained (GBP 414.67 (EUR 554.53)) and per ceftriaxone-sparing treatment (GBP 11.29 (EUR 15.09)) but with treatment failures (n = 34) and suboptimal treatments (n = 706).ConclusionsAMR POCT may enable improved antibiotic stewardship, but require net health system investment. A small reduction in test cost would enable monotherapy AMR POCT strategies to be cost-saving.

Preventive Antibiotics in Stroke Study (PASS): A cost-effectiveness study.

OBJECTIVE: To evaluate the cost-effectiveness of preventive ceftriaxone vs standard stroke unit care without preventive antimicrobial therapy in acute stroke patients. METHODS: In this multicenter, randomized, open-label trial with masked endpoint assessment, 2,550 patients with acute stroke were included between 2010 and 2014. Economic evaluation was performed from a societal perspective with a time horizon of 3 months. Volumes and costs of direct, indirect, medical, and nonmedical care were assessed. Primary outcome was cost per unit of the modified Rankin Scale (mRS) and per quality-adjusted life year (QALY) for cost-effectiveness and cost-utility analysis. Incremental cost-effectiveness analyses were performed. RESULTS: A total of 2,538 patients were available for the intention-to-treat analysis. For the cost-effectiveness analysis, 2,538 patients were available for in-hospital resource use and 1,453 for other resource use. Use of institutional care resources, out-of-pocket expenses, and productivity losses was comparable between treatment groups. The mean score on mRS was 2.38 (95% confidence interval [CI] 2.31-2.44) vs 2.44 (95% CI 2.37-2.51) in the ceftriaxone vs control group, the decrease by 0.06 (95% CI -0.04 to 0.16) in favor of ceftriaxone treatment being nonsignificant. However, the number of QALYs was 0.163 (95% CI 0.159-0.166) vs 0.155 (95% CI 0.152-0.158) in the ceftriaxone vs control group, with the difference of 0.008 (95% CI 0.003-0.012) in favor of ceftriaxone (p = 0.006) at 3 months. The probability of ceftriaxone being cost-effective ranged between 0.67 and 0.89. Probability of 0.75 was attained at a willing-to-pay level of €2,290 per unit decrease in the mRS score and of €12,200 per QALY. CONCLUSIONS: Preventive ceftriaxone has a probability of 0.7 of being less costly than standard treatment per unit decrease in mRS and per QALY gained.

Prospective evaluation of Ceftriaxone use in medical and emergency wards of Gondar university referral hospital, Ethiopia.

Ceftriaxone is among the most commonly utilized antibiotics owing to its high potency, wide spectrum of activity, and low risk of toxicity. It is used to treat different types of bacterial infections including pneumonia, bone infections, abdominal infections, Skin and soft tissue infections, urinary tract infections. However, evidence around the globe shows the misuse of Ceftriaxone. This study aimed at evaluating the appropriateness of ceftriaxone use in medical and emergency wards of Gondar university referral hospital (GURH), Northwest Ethiopia. A prospective, cross-sectional study design was employed to evaluate the use of ceftriaxone. The medical records of patients who received ceftriaxone were reviewed prospectively between January 1 and March 30, 2017. Appropriateness of ceftriaxone use was evaluated as per the protocol developed from current treatment guidelines. A total of 390 patients' medical records were reviewed. The utilization rate of ceftriaxone was found to be high with a point prevalence of 59%. Ceftriaxone was empirically used in 79.5% of cases. The most common indications of Ceftriaxone were respiratory tract infections (29.3%), central nervous system infections (24.1%), and prophylactic indications (16.4%). The mean duration of ceftriaxone therapy in our study was 11.47 days, with a range of 1-52 days. More than two-thirds (80.2%) of ceftriaxone use were found to be inappropriate and majority of unjustified ceftriaxone use emanated from inappropriate frequency of administration (78.3%), absence of culture and sensitivity test (68.7%), and duration of therapy (47%). Empiric treatment with ceftriaxone and the presence of coadministered drugs was significantly associated with its inappropriate use. The present study revealed a very high rate of inappropriate use of ceftriaxone which may potentially lead to emergence of drug-resistant microorganisms and ultimately exposes the patient to treatment failure and increased cost of therapy.

Once-Daily Ceftriaxone Plus Metronidazole Versus Ertapenem and/or Cefoxitin for Pediatric Appendicitis.

BACKGROUND: Appendicitis is a common surgical emergency in pediatric patients, and broad-spectrum antibiotic therapy is warranted in their care. A simplified once-daily regimen of ceftriaxone and metronidazole (CTX plus MTZ) is cost effective in perforated patients. The goal of this evaluation is to compare a historic regimen of cefoxitin (CFX) in nonperforated cases and ertapenem (ERT) in perforated and abscessed cases with CTX plus MTZ for all cases in terms of efficacy and cost. METHODS: A retrospective review compared outcomes of nonperforated, perforated, and abscessed cases who received the historic regimen or CTX plus MTZ. Length of stay, time to afebrile, time to full feeds, postoperative abscess, and wound infection rates, inpatient readmissions, and antibiotic costs were evaluated. RESULTS: There were a total of 841 cases reviewed (494 nonperforated, 247 perforated, and 100 abscessed). Overall, the CTX plus MTZ group had a shorter time to afebrile (P < .001). Treatment groups did not differ in length of stay. Postoperative abscess rates were similar between groups (4.1% vs 3.3%, not significant). Other postoperative complications were similar between groups. Total antibiotic cost savings were over $110 000 during the study period (from November 2010 to June 2013). CONCLUSIONS: Both CFX and/or ERT and CTX plus MTZ result in low abscess and complication rates, suggesting both are effective strategies. Treatment with CTX plus MTZ results in a shorter time to afebrile, while also providing significant antibiotic cost savings. Ceftriaxone plus MTZ is a streamlined, cost-effective regimen in the treatment of nonperforated, perforated, and abscessed appendicitis.

Gentamicin versus ceftriaxone for the treatment of gonorrhoea (G-TOG trial): study protocol for a randomised trial.

BACKGROUND: Gonorrhoea is a common sexually transmitted infection which causes genital pain and discomfort; in women it can also lead to pelvic inflammatory disease and infertility, and in men to epididymo-orchitis. Current treatment is with ceftriaxone, but there is increasing evidence of antimicrobial resistance which is reducing its effectiveness against gonorrhoea. A small, but increasing, number of patients have already been found to have highly resistant strains of gonorrhoea which has been associated with clinical failure. This trial aims to determine whether gentamicin is not clinically worse than ceftriaxone in the treatment of gonorrhoea. METHODS/DESIGN: This is a blinded, two-arm, multicentre, noninferiority randomised trial. Patients are eligible if they are aged 16-70 years with a diagnosis of genital, pharyngeal and/or rectal gonorrhoea. Exclusion criteria are: known concurrent sexually transmitted infection(s) (excluding chlamydia); bacterial vaginosis and/or Trichomonas vaginalis infection; contraindications or an allergy to gentamicin, ceftriaxone, azithromycin or lidocaine; pregnancy or breastfeeding; complicated gonorrhoeal infection; weight under 40 kg; use of ceftriaxone, gentamicin or azithromycin within the preceding 28 days. Randomisation is to receive a single intramuscular injection of either gentamicin or ceftriaxone, all participants receive 1 g oral azithromycin as standard treatment. The estimated sample size is 720 participants (noninferiority limit 5%). The primary outcome is clearance of Neisseria gonorrhoeae at all infected sites by a negative Nucleic Acid Amplification Test, 2 weeks post treatment. Secondary outcomes include clinical resolution of symptoms, frequency of adverse events, tolerability of therapy, relationship between clinical effectiveness and antibiotic minimum inhibitory concentration for N. gonorrhoeae, and cost-effectiveness. DISCUSSION: The options for future treatment of gonorrhoea are limited. Results from this randomised trial will demonstrate whether gentamicin is not clinically worse than ceftriaxone for the treatment of gonorrhoea. This will inform clinical practice and policy for the treatment of gonorrhoea when current therapy with cephalosporins is no longer effective, or is contraindicated. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number - ISRCTN51783227 , Registered on 18 September 2014. Current protocol version 2.0 17 June 2015.

Cost-Effectiveness of Dual Antimicrobial Therapy for Gonococcal Infections Among Men Who Have Sex With Men in the Netherlands.

BACKGROUND: In response to the rising threat of resistance to first-line antibiotics for gonorrhea, international guidelines recommend dual antimicrobial therapy. However, some countries continue to recommend monotherapy. We assess the cost-effectiveness of dual therapy with ceftriaxone and azithromycin compared with monotherapy with ceftriaxone, for control of gonorrhea among men who have sex with men in the Netherlands. METHODS: We developed a transmission model and calculated the numbers of new gonorrhea infections, consultations at health care specialists, tests, and antibiotic doses. With these numbers, we calculated costs and quality-adjusted life-years (QALY) with each treatment; and the incremental cost-effectiveness ratio (ICER) of dual therapy compared to monotherapy. The impact of gonorrhea on human immunodeficiency virus transmission was not included in the model. RESULTS: In the absence of initial resistance, dual therapy can delay the spread of ceftriaxone resistance by at least 15 years, compared to monotherapy. In the beginning, when there is no resistance, dual therapy results in high additional costs, without any QALY gains. When resistance spreads over time, the additional costs of dual therapy decline, the gained QALYs increase, the ICER drops off and, after 50 years, falls below &OV0556;20,000 per QALY gained. If azithromycin resistance is initially prevalent, resistance to the first-line treatment rises almost equally fast with both treatment strategies and the ICER remains extremely high. CONCLUSIONS: Compared with ceftriaxone monotherapy, dual therapy with ceftriaxone and azithromycin can considerably delay the spread of ceftriaxone resistance, but may only be cost-effective in the long run and in the absence of initial resistance.

Assessment of the price-efficacy relationship for multiple brands of ceftriaxone sodium in Kabul: a cross-sectional study.

BACKGROUND: Most medicines are imported for health service practices in Afghanistan. A major concern for patients and practitioners in Kabul is the wide brand assortment and price range choices for the same drug. Ceftriaxone sodium is a broadly used antibiotic for infections caused by certain types of gram-positive and gram-negative bacteria. It is available in Kabul in a range of brands and prices. The objective of this study was to assess the relationship between cost/brand name and efficacy of this antibiotic. METHODS: 40 brands of ceftriaxone, obtained from Kabul's main pharmacy, were derived from 12 countries including Pakistan, Turkey, India, and China. Ten samples/brand were tested for efficacy by the minimal bactericidal concentration assay against a sensitive strain of Staphylococcus aureus according to the Clinical Institute and Laboratory Standards Protocols. Efficacy data were obtained by inoculating suspensions of S. aureus grown in Mueller-Hinton medium with various concentrations (6.25-800 mcg/ml) of each brand followed by incubation at 37 °C for 18-24 h. Aliquots of inoculated cultures were transferred to agar plates, incubated at 37 °C for 18-24 h and visible colonies counted. Results were analyzed using ANOVA, Student's t test, and Pearson correlation by SPSS 19. A p value ≤ 0.05 was considered statistically significant. RESULTS: Ceftriaxone sodium price varied from 20-270 Afghanis/brand (average price = 69.80 Afghanis/brand). Of the 40 brands tested, 10 (25 %) were not registered with the General Directorate of Pharmaceutical Affairs of the Ministry of Public Health in Afghanistan. More importantly, we observed no statistically significant difference in efficacy against S. aureus among these brands (p = 0.59). CONCLUSIONS: Our study showed no significant correlation among price, brand, and efficacy of ceftriaxone sodium against S. aureus, an important consideration when treating S. aureus infection in Afghanistan and elsewhere. Differences in brand prices are likely due to other factors including manufacturing and exportation costs, regulations of good manufacturing practice and seller's profit ceiling and patient preferences. Based on our results, we suggest that further chemical and clinical studies of ceftriaxone sodium brands are warranted and recommend that physicians consider alternative cost-effective generic brands in patient prescriptions.

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.

Association of clinical practice guidelines with emergency department management of febrile infants ≤56 days of age.

BACKGROUND: Differences among febrile infant institutional clinical practice guidelines (CPGs) may contribute to practice variation and increased healthcare costs. OBJECTIVE: Determine the association between pediatric emergency department (ED) CPGs and laboratory testing, hospitalization, ceftriaxone use, and costs in febrile infants. DESIGN: Retrospective cross-sectional study in 2013. SETTING: Thirty-three hospitals in the Pediatric Health Information System. PATIENTS: Infants aged ≤56 days with a diagnosis of fever. EXPOSURES: The presence and content of ED-based febrile infant CPGs assessed by electronic survey. MEASUREMENTS: Using generalized estimating equations, we evaluated the association between CPG recommendations and rates of urine, blood, cerebrospinal fluid (CSF) testing, hospitalization, and ceftriaxone use at ED discharge in 2 age groups: ≤28 days and 29 to 56 days. We also assessed CPG impact on healthcare costs. RESULTS: We included 9377 ED visits; 21 of 33 EDs (63.6%) had a CPG. For neonates ≤28 days, CPG recommendations did not vary and were not associated with differences in testing, hospitalization, or costs. Among infants 29 to 56 days, CPG recommendations for CSF testing and ceftriaxone use varied. CSF testing occurred less often at EDs with CPGs recommending limited testing compared to hospitals without CPGs (adjusted odds ratio: 0.5, 95% confidence interval: 0.3-0.8). Ceftriaxone use at ED discharge varied significantly based on CPG recommendations. Costs were higher for admitted and discharged infants 29 to 56 days old at hospitals with CPGs. CONCLUSIONS: CPG recommendations for febrile infants 29 to 56 days old vary across institutions for CSF testing and ceftriaxone use, correlating with observed practice variation. CPGs were not associated with lower healthcare costs.

Estimating costs associated with a community outbreak of meningococcal disease in a colombian Caribbean city.

Meningococcal disease is a serious and potentially life-threatening infection that is caused by the bacterium Neisseria meningitidis (N. meningitidis), and it can cause meningitis, meningococcaemia outbreaks and epidemics. The disease is fatal in 9-12% of cases and with a death rate of up to 40% among patients with meningococcaemia. The objective of this study was to estimate the costs of a meningococcal outbreak that occurred in a Caribbean city of Colombia. We contacted experts involved in the outbreak and asked them specific questions about the diagnosis and treatment for meningococcal cases during the outbreak. Estimates of costs of the outbreak were also based on extensive review of medical records available during the outbreak. The costs associated with the outbreak were divided into the cost of the disease response phase and the cost of the disease surveillance phase. The costs associated with the outbreak control and surveillance were expressed in US$ (2011) as cost per 1,000 inhabitants. The average age of patients was 4.6 years (SD 3.5); 50% of the cases died; 50% of the cases were reported to have meningitis (3/6); 33% were diagnosed with meningococcaemia and myocarditis (2/6); 50% of the cases had bacteraemia (3/6); 66% of the cases had a culture specimen positive for Neisseria meningitidis; 5 of the 6 cases had RT-PCR positive for N. meningitidis. All N. meningitidis were serogroup B; 50 doses of ceftriaxone were administered as prophylaxis. Vaccine was not available at the time. The costs associated with control of the outbreak were estimated at US$ 0.8 per 1,000 inhabitants, disease surveillance at US$ 4.1 per 1,000 inhabitants, and healthcare costs at US$ 5.1 per 1,000 inhabitants. The costs associated with meningococcal outbreaks are substantial, and the outbreaks should be prevented. The mass chemoprophylaxis implemented helped control the outbreak.

Update of the Preventive Antibiotics in Stroke Study (PASS): statistical analysis plan.

BACKGROUND: Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were still blinded for all outcomes. RESULTS: The primary outcome is the score on the modified Rankin Scale (mRS), assessed by ordinal logistic regression analysis according to a proportional odds model. Secondary analysis of the primary outcome is the score on the mRS dichotomized as a favorable outcome (mRS 0 to 2) versus unfavorable outcome (mRS 3 to 6). Secondary outcome measures are death rate at discharge and 3 months, infection rate during hospital admission, length of hospital admission, volume of post-stroke care, use of antibiotics during hospital stay, quality-adjusted life years and costs. Complications of treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) are reported as safety outcomes. CONCLUSIONS: The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection and will be analyzed according to this pre-specified SAP. TRIAL REGISTRATION: Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.

Determinants, outcomes and costs of ceftriaxone v. amoxicillin-clavulanate in the treatment of community-acquired pneumonia at Witbank Hospital.

BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of death and morbidity worldwide. Treatment is centred on antibiotics with ceftriaxone and amoxicillin-clavulanate being some of the most commonly prescribed agents. OBJECTIVE: To compare treatment outcomes and costs in patients receiving either of these two antibiotics at Witbank Hospital (WH). METHODS: A total of 200 randomly selected adult patient files (100 receiving ceftriaxone and 100 amoxicillin-clavulanate) recording a diagnosis of CAP were studied to determine the length of hospital stay, comorbid conditions and treatment outcomes. A descriptive and comparable analysis was performed. RESULTS: Male gender, higher CURB-65 scores and death were associated with the use of ceftriaxone. Severity of disease and previous antibiotic exposure influenced the duration of hospital admission. CONCLUSION: Gender and severity of disease (based on the CURB-65 score) were the determinants of antibiotic choice at WH. Male gender increased the likelihood of being treated with ceftriaxone, as did a CURB-65 score of > 2. There were no differences in the outcomes of CAP patients treated with ceftriaxone compared with those treated with amoxicillin-clavulanate. Irrespective of antibiotic used, gender and severity of disease influenced treatment outcomes. Male gender was associated with a higher mortality and longer hospital stay. The average duration of stay for both antibiotics was not significantly different. Thus, only level 1 and 2 costs need to be considered when comparing the two regimens. On this basis, ceftriaxone was cheaper than amoxicillin-clavulanate.

Oral versus intravenous antibiotics for patients with Klebsiella pneumoniae liver abscess: study protocol for a randomized controlled trial.

BACKGROUND: Klebsiella pneumoniae liver abscess is the most common etiology of liver abscess in Singapore and much of Asia, and its incidence is increasing. Current management includes prolonged intravenous antibiotic therapy, but there is limited evidence to guide oral conversion. The implicated K1/K2 capsule strain of Klebsiella pneumoniae is almost universally susceptible to ciprofloxacin, an antibiotic with high oral bioavailability. Our primary aim is to compare the efficacy of early (< one week) step-down to oral antibiotics, to continuing four weeks of intravenous antibiotics, in patients with Klebsiella liver abscess. METHODS/DESIGN: The study is designed as a multi-center randomized open-label active comparator-controlled non-inferiority trial, with a non-inferiority margin of 12%. Eligible participants will be inpatients over the age of 21 with a CT or ultrasound scan suggestive of a liver abscess, and Klebsiella pneumoniae isolated from abscess fluid or blood. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. Participants randomized to active control will receive IV ceftriaxone 2 grams daily to complete a total of four weeks of IV antibiotics. Participants randomized to intervention will be immediately converted to oral ciprofloxacin 750 mg twice daily. At Week four, all participants will undergo abdominal imaging and be assessed for clinical response (CRP < 20 mg/l, absence of fever, plus scan showing that the maximal diameter of the abscess has reduced). If criteria are met, antibiotics are stopped; if not, oral antibiotics are continued, with reassessment for clinical response fortnightly. If criteria for clinical response are met by Week 12, the primary endpoint of clinical cure is met. A cost analysis will be performed to assess the cost saving of early conversion to oral antibiotics, and a quality of life analysis will be performed to assess whether treatment with oral antibiotics is less burdensome than prolonged IV antibiotics. DISCUSSION: Our results would help inform local and international practice guidelines regarding the optimal antibiotic management of Klebsiella liver abscess. A finding of non-inferiority may translate to the wider adoption of a more cost-effective strategy that reduces hospital length of stay and improves patient-centered outcomes and satisfaction. TRIAL REGISTRATION: Clinical trials gov NCT01723150.

The impact of a nationwide antibiotic restriction program on antibiotic usage and resistance against nosocomial pathogens in Turkey.

PURPOSE: Antimicrobial resistance among microorganisms is a global concern. In 2003, a nationwide antibiotic restriction program (NARP) was released in Turkey. In this study we evaluated the effect of NARP on antibiotic consumption, antimicrobial resistance, and cost. MATERIALS AND METHODS: The data obtained from all of the four university hospitals, and one referral tertiary-care educational state hospital in Ankara. Antimicrobial resistance profiles of 14,233 selected microorganisms all grown in blood cultures and antibiotic consumption from 2001 to 2005 were analyzed retrospectively. RESULTS: A negative correlation was observed between the ceftriaxone consumption and the prevalence of ceftriaxone resistant E.coli and Klebsiella spp. (rho:-0.395, p:0.332 and rho:-0.627, p:0.037, respectively). The decreased usage of carbapenems was correlated with decreased carbapenems-resistant Pseudomonas spp. and Acinetobacter spp (rho:0.155, p:0.712 and rho:0.180, p:0.668, respectively for imipenem). Methicillin resistance rates of S.aureus were decreased from 44% to 41%. After two years of NARP 5,389,155.82 USD saving occurred. CONCLUSION: NARP is effective in lowering the costs and antibiotic resistance.

A prospective, controlled, randomized, non-blind, comparative study of the efficacy and safety of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in empirical therapy for febrile neutropenic patients.

BACKGROUND: Empirical antibiotic treatment for febrile neutropenia is well established. The best regimen is still controversial. The purpose of this study was to evaluate the efficacy, safety, and cost of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in neutropenic febrile patients. METHODS: Ninety-five patients with febrile neutropenia were included in a prospective, controlled, randomized, non-blind, comparative study. Patients were randomly assigned to one of the treatment groups (63 to the ceftriaxone/ciprofloxacin group and 32 to the ceftazidime/amikacin group) and evaluated as successes or failures according to defined criteria. Daily assessments were made of all patients and all adverse events were recorded. RESULTS: The overall incidence of documented infections was 45.9%: 24/47 (51.1%) in the ceftriaxone/ciprofloxacin group and 10/27 (37%) in the ceftazidime/amikacin group. There was a significant difference in clinical efficacy between the groups (p=0.011) at the end of therapy. The ceftriaxone/ciprofloxacin group had an overall incidence of resolution and improvement of 95.7% in comparison to 75% in the ceftazidime/amikacin group. Thirty-nine organisms were isolated, 26 (66.67%) gram-negative and 13 (33.33%) gram-positive. There was a low incidence of adverse events in both groups. CONCLUSION: The combination of a single, high dose of ceftriaxone plus ciprofloxacin daily was more effective than the standard combination of thrice daily ceftazidime plus amikacin with no significant adverse events in either group.

Comparison of ceftriaxone versus triple drug regimen in the prevention of cesarean section infectious morbidities.

OBJECTIVE: To compare the effectiveness of single dose ceftriaxone versus multiple doses of ampiclox, gentamicin, and metronidazole to prevent infectious morbidity at elective cesarean section. METHODS: This was a randomized clinical trial involving 200 pregnant women who had an elective cesarean section for various reasons during the study period. Outcome measures included endometritis, urinary tract infections, febrile morbidities, wound infections, duration of hospital stay, and cost of antibiotic therapy. Data were managed using SPSS. RESULTS: There was no statistically significant difference in the mean duration of hospital stay between the two groups, but a significant statistical difference was found in the mean cost of antibiotic treatment ($15 for the combination and $9 for ceftriaxone; p = 0.000), with the group of patients taking a single dose of ceftriaxone (ROPHEX) having a lower mean cost of treatment than those taking a combination of ampiclox, gentamicin, and metronidazole. The study groups did not differ significantly in the incidence of endometritis (14% versus 15%), urinary tract infection (11% versus 15%), wound infections (7% versus 8%), febrile morbidity (7% versus 6%), and peritonitis (0% versus 0%). CONCLUSION: Single dose ceftriaxone was as effective as a combination of ampiclox, gentamicin, and metronidazole in preventing post-elective cesarean section complications.

Single daily dosing ceftriaxone and metronidazole vs standard triple antibiotic regimen for perforated appendicitis in children: a prospective randomized trial.

INTRODUCTION: Appendicitis is the most common emergency condition in children. Historically, a 3-drug regimen consisting of ampicillin, gentamicin, and clindamycin (AGC) has been used postoperatively for perforated appendicitis. A retrospective review at our institution has found single day dosing of ceftriaxone and metronidazole (CM) to be a more simple and cost-effective antibiotic strategy. Therefore, we performed a prospective, randomized trial to compare efficacy and cost-effectiveness of these 2 regimens. METHODS: After internal review board approval (IRB no. 04 12-149), children found to have perforated appendicitis at appendectomy were randomized to either once daily dosing of CM (2 total doses per day) or standard dosing of AGC (11 total doses per day). Perforation was defined as an identifiable hole in the appendix. The operative approach (laparoscopic), length of antibiotic use, and criteria for discharge were standardized for the groups. Based on our retrospective analysis using length of postoperative hospitalization as a primary end point, a sample size of 100 patients was calculated for an alpha of .5 and a power of 0.82. RESULTS: One hundred patients underwent laparoscopic appendectomy for perforated appendicitis. On presentation, there were no differences in sex distribution, days of symptoms, temperature, or leukocyte count. There was no difference in abscess rate or wound infections between groups. The CM group resulted in significantly less antibiotic charges then the AGC group. CONCLUSIONS: Once daily dosing with the 2-drug regimen (CM) offers a more efficient, cost-effective antibiotic management in children with perforated appendicitis without compromising infection control when compared to a traditional 3-drug regimen.

A cost-minimisation analysis comparing moxifloxacin with levofloxacin plus ceftriaxone for the treatment of patients with community-acquired pneumonia in Germany: results from the MOTIV trial.

OBJECTIVE: This study presents a cost-minimisation analysis of moxifloxacin compared to combination treatment with levofloxacin and ceftriaxone in patients hospitalised with community-acquired pneumonia (CAP) in Germany. RESEARCH DESIGN AND METHODS: In the MOTIV study, 738 adult patients with CAP requiring hospitalisation and initial parenteral antibiotic therapy were randomised to sequential IV/oral therapy with either moxifloxacin (n = 368), or levofloxacin and ceftriaxone (n = 365). The primary effectiveness endpoint was the proportion of patients demonstrating clinical improvement 5-7 days after the completion of study treatment. Subgroup analysis considered patients with severe CAP according to pneumonia severity index (PSI) risk class IV and V, microbiologically proven infection, a history of chronic obstructive pulmonary disease, and a history of cardiovascular disease. The analysis included the cost of study medication, hospital stay, readmission and inpatient procedures and diagnostics. Event frequency in the study was multiplied by German unit costs to estimate per-patient expenditure. The analysis was conducted from a hospital perspective. Sensitivity analysis investigated the effect of costing from an insurer perspective. RESULTS: No significant difference was found in the percentage of successfully treated patients. Average per patient cost was euro 2190 for the moxifloxacin group, and euro 2619 for the levofloxacin + ceftriaxone group (difference -euro 430, 95% CI: -euro 138, -euro 740; p < 0.05). Variability in total costs was wide, with some patients accruing up to euro 18,000. Medication cost was significantly lower with moxifloxacin than levofloxacin + ceftriaxone (-euro 470, 95% CI: -euro 522, -euro 421), and accounted for between 15 and 30% of total costs. CONCLUSIONS: In this analysis of patients hospitalised with CAP in Germany, treatment with moxifloxacin was significantly less costly than treatment with levofloxacin and ceftriaxone.