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.

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.

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.

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.

Intravenous push antibiotics in the emergency department: Education and implementation.

PURPOSE: Intravenous push antibiotics can serve as an alternative to intravenous piggyback antibiotics while providing the same pharmacodynamics and adverse effect profile, easing shortage pressures and decreasing order to administration time, as well as representing a potential cost savings. The purpose of this study was to determine whether intravenous push antibiotics could decrease the time from an order to the start of administration compared to piggyback antibiotics in emergency departments. This study also measured the cost savings of antibiotic preparation and administration and assessed nursing satisfaction when using intravenous push antibiotics. METHODS: Sample instances of use of intravenous push and piggyback antibiotics were identified. Patients were included if they were 18 years of age or older and received at least a single dose of intravenous push or piggyback ceftriaxone, cefepime, cefazolin, or meropenem in one of the institution's emergency departments. The primary outcome of the study was to compare the time from the order to the start of administration of intravenous push vs piggyback antibiotics. The secondary outcome was to compare the cost of antibiotic preparation for the 2 methods. RESULTS: The intravenous push and piggyback groups each had 43 patients. The time from the order to the start of administration decreased from 74 (interquartile range, 29-114) minutes in the piggyback group to 31 (interquartile range, 21-52) minutes in the push group (P = 0.003). When the estimated monthly cost savings for ceftriaxone, cefepime, and meropenem were added together, across the emergency departments, an estimated $227,930.88 is saved per year when using intravenous push antibiotics. CONCLUSION: Intravenous push antibiotics decrease the time from ordering to the start of administration and result in significant cost savings.

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.

Cost-effectiveness of oral gemifloxacin versus intravenous ceftriaxone followed by oral cefuroxime with/without a macrolide for the treatment of hospitalized patients with community-acquired pneumonia.

We studied the cost-effectiveness of oral gemifloxacin with intravenous ceftriaxone followed by oral cefuroxime with or without a macrolide to treat patients hospitalized with community-acquired pneumonia. Data were prospectively collected as part of a randomized multicenter study. The costs evaluated included antimicrobial acquisition (1st level); plus preparation, dispensing, and administration costs, and treatment of antimicrobial-related adverse events and clinical failures (2nd level); plus per diem costs for hospital stay related to study drug administration (3rd level). At follow-up, clinical success was similar between gemifloxacin (76.9%)- and ceftriaxone (79.1%)-treated patients. The median 1st-level costs for gemifloxacin and ceftriaxone were $136 and $470 (P<0.001), respectively. For the 2nd level, these costs were $158 and $542 (P<0.001), and for the 3rd level, these were $5052 and $5789 (P=0.025), respectively. The median cost per expected success was $6568 for gemifloxacin and $7321 for ceftriaxone (P=0.29). Oral gemifloxacin is clinically effective and has an economic advantage over ceftriaxone, followed by oral cefuroxime with or without a macrolide.

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 cefepime versus ceftriaxone for nursing home-acquired pneumonia.

OBJECTIVES: To compare once-daily intramuscular cefepime with ceftriaxone controls. DESIGN: Double-blind study. SETTING: Six skilled nursing facilities. PARTICIPANTS: Residents aged 60 and older with nursing home-acquired pneumonia. INTERVENTION: Cultures were obtained, and patients were randomized to cefepime or ceftriaxone 1 g intramuscularly every 24 hours. MEASUREMENTS: Clinical success: cure or improvement. Cure was defined as complete resolution of all symptoms and signs of pneumonia or a return to the patient's baseline state. Improvement was defined as clear improvement but incomplete resolution of all pretherapy symptoms or signs or incomplete return to the patient's usual baseline status. Safety and pharmacoeconomics were also assessed. RESULTS: Sixty-nine patients were randomized; 61 were evaluable: (32 to cefepime, 29 ceftriaxone). Patients were predominately female (76%). They had a mean age+/-standard deviation of 85+/-6, with a mean 5.8+/-1.9 comorbidities; they had age-appropriate renal dysfunction, with a mean estimated creatinine clearance of 35+/-7 mL/min. Clinical success occurred in 78% of cefepime- and 66% of ceftriaxone-treated patients (P=.39). Fifty-seven patients (93%) were switched to oral antibiotics after 3 days. Antibiotic-related adverse events occurred in 5% of patients. Seven patients (11.5%) were hospitalized. The overall mortality rate was 8%. Mean antibiotic costs were 117+/-40 dollars for cefepime- and 215+/-68 dollars for ceftriaxone-treated patients (P<.001). Cost-effectiveness analysis of total costs showed that cefepime would cost 597 dollars and ceftriaxone 1,709 dollars per expected successfully treated patient. One- and two-way sensitivity analyses using a generic price for ceftriaxone and improving its comparative efficacy revealed that the results were robust. CONCLUSIONS: Once-daily cefepime was a cost-effective alternative to ceftriaxone for the treatment of elderly nursing home residents who developed pneumonia and did not require hospitalization.

Retrospective analysis of a new antibiotic chemoprophylaxis regimen in 170 patients undergoing endoscopic endonasal transsphenoidal surgery.

BACKGROUND: The aim of this study is to evaluate the rate of infectious complications post endoscopic transspheinodal neurosurgery in patients receiving a new antibiotic chemoprophylaxis regimen. METHODS: Clinical records of 170 patients who received prophylaxis with a third-generation cephalosporin plus aminoglycoside (160 cases) or alone (10 cases) were retrospectively analyzed. Twenty-eight patients (16.4%) had CSF leakage. The postsurgical follow-up ranged from 3 months to 4 years. RESULTS: Of 170 patients, 2 (1.17%) developed infectious complications: 1 case of meningitis by Staphylococcus epidermidis and 1 case of sphenoid sinusitis (without microbiological diagnosis). In addition, asymptomatic sphenoid sinusitis was diagnosed in 2 other patients. The cost ranged from 22.50 to 33.34 euros/d. CONCLUSIONS: The rate of infectious complications was very low in patients receiving prophylaxis with a third-generation cephalosporin plus aminoglycoside or alone; because of the broad-spectrum of antibiotics and their high cost, this regimen could be used in at-risk patients (eg, smokers, patients with cerebrospinal leak, or patients with Cushing diseases).

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.

Doxycycline versus ceftriaxone for the treatment of patients with chronic Lyme borreliosis.

BACKGROUND: Therapeutic guidelines for treatment of late manifestations of Lyme borreliosis have not yet become well established. Patients with symptoms suggesting central nervous system involvement are often treated with courses of intravenous ceftriaxone. This is an expensive treatment approach with potentially severe side effects. We compared the efficacy, side effects and costs of doxycycline and ceftriaxone in the treatment of such patients. PATIENTS AND METHODS: Adult patients qualified for the study if they had nonspecific symptoms suggesting central nervous system involvement for more than six months (but without overt clinical signs of the involvement), had positive serum borrelial antibody titers and/or erythema migrans prior to the onset of symptoms, had not been previously treated with antibiotics and did not have pleocytosis in the cerebrospinal fluid. Patients were given either 100 mg of oral doxycycline twice daily for 4 weeks (23 patients) or 2 g of intravenous ceftriaxone daily for 2 weeks followed by 100 mg of doxycycline twice daily for another 2 weeks (23 patients). Clinical outcome was assessed during a 12-month follow-up period. RESULTS: Improvement in the frequency and/or the intensity of symptoms was reported by more than two-thirds of the 46 patients enrolled in the study. The two treatment regimens were found to be correspondingly effective. Photosensitivity reactions and gastrointestinal symptoms were noted more often among patients receiving doxycycline than in those receiving ceftriaxone. Treatment with doxycycline proved to be much cheaper than with ceftriaxone. CONCLUSIONS: In patients with previously untreated chronic Lyme borreliosis with symptoms suggesting central nervous system involvement but without overt clinical signs of it, and without pleocytosis in the cerebrospinal fluid, treatment with doxycycline is as effective as with ceftriaxone. Treatment with doxycycline is cheap and relatively safe, but gastrointestinal symptoms and photosensitivity reactions can be expected more often than with ceftriaxone.

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.

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.

A cost-minimization analysis comparing azithromycin-based and levofloxacin-based protocols for the treatment of patients hospitalized with community-acquired pneumonia: results from the CAP-IN trial.

BACKGROUND: A randomized trial was performed comparing azithromycin and levofloxacin for treating moderately to severely ill patients hospitalized with community-acquired pneumonia. This is a cost-minimization analysis comparing those regimens. METHODS: The cost-minimization analysis compares 81 patients receiving sequential therapy with IV azithromycin plus IV ceftriaxone followed by oral azithromycin with 82 patients receiving IV levofloxacin followed by oral levofloxacin, all with complete economic data over approximately 30 days, including information about hospitalization, study medications, home care, postdischarge utilization, and lost productivity. Units of utilization were multiplied by unit prices in order to estimate cost per patient. These total costs were compared using a two-sample t test. RESULTS: Direct medical costs of the azithromycin group were 2,481 US dollars less than the corresponding costs in the levofloxacin group (p = 0.03; 95% confidence interval, 238 US dollars to 4,724 US dollars). Most of the cost difference (2,300 US dollars) is attributable to hospital days, with the majority of these days being spent on the general medicine wards. The precise magnitude of the cost advantage attributable to azithromycin, if any, depends on both the reduction in length of hospital stay and its associated daily cost. CONCLUSIONS: Azithromycin was no more costly than levofloxacin, and perhaps less so. Cost is but one of many factors that should be considered by clinicians in decisions involving any individual patient.

Ceftriaxone prophylaxis in abdominal, cardiovascular, thoracic, orthopaedic, neurosurgical and general surgery: a review of practice 1996 - 2003.

The microbiology, efficacy and cost-effectiveness of ceftriaxone prophylaxis were compared with those of alternative antimicrobial agents in abdominal, cardiovascular, thoracic, orthopaedic, neurosurgical and general surgical procedures published since 1996. Ceftriaxone was compared with cefazolin +/- metronidazole, cefoxitin, cefuroxime, ceftazidime, cefotaxime, cefepime + metronidazole, penicillins, ticarcillin/clavulanic acid, ampicillin/sulbactam, vancomycin and combined clindamycin/gentamicin. Ceftriaxone, used primarily as 'single shot prophylaxis', was at least as clinically effective if not better than the comparative single- and multiple-dose agents over the broad range of surgical procedures. Furthermore the overall cost of ceftriaxone prophylaxis has often been shown to be markedly less than comparators, despite the relatively high acquisition cost of ceftriaxoe, when factors other than acquisition cost were considered. Advances in surgical techniques, the changes in bacterial ecology in hospitals, the spread of bacterial resistance and the substantial increase in the surgical population at risk suggest that third generation cephalosporins, particularly ceftriaxone, should be taken into consideration for surgical prophylaxis.

In vitro activity, pharmacokinetics, clinical efficacy, safety and pharmacoeconomics of ceftriaxone compared with third and fourth generation cephalosporins: review.

Due to their wide spectrum of activity, good pharmacokinetics, established clinical efficacy and high tolerability, cephalosporins are among the most widely used antibiotics worldwide. The third and fourth generation cephalosporins are predominantly parenteral agents, administered two or three times daily, used in the treatment of a wide range of moderate to severe infections. Ceftriaxone, a third generation cephalosporin, is unique in exhibiting an unusually long elimination half-life that allows for once-daily administration. Among third generation cephalosporins, ceftazidime and cefoperazone are unusual among cephalosporins in possessing activity, albeit moderate, against Pseudomonas aeruginosa. However, both of these agents also exhibit marked loss of activity against Gram-negative organisms producing high levels of Class A or C beta-lactamases. Sulperazone, a 1:1 combination of cefoperazone and the beta-lactamase inhibitor sulbactam, is more resistant to attack by Class A beta-lactamases but remains vulnerable to isolates producing Class C beta-lactamases. Ceftriaxone exhibits the widest antibacterial spectrum of third generation cephalosporins and this is reflected in clinical responses. Cefoperazone and sulperazone exhibit the poorest clinical responses. Although the fourth generation cephalosporins cefpirome and cefepime exhibit enhanced stability to bacterial beta-lactamases and marginally enhanced in vitro antibacterial activity over ceftriaxone, there is no clinical advantage in terms of clinical or bacteriological success. The cephalosporins are well tolerated, with few and generally transient adverse effects; the major exception being haematological abnormalities including blood coagulation disorders associated with cefoperazone. Several pharmacoeconomic studies indicate that the once-daily dosing regimen required for ceftriaxone is the major factor responsible for its cost-effectiveness over third and fourth generation cephalosporins.

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.