Costs and cost-effectiveness of management of possible serious bacterial infections in young infants in outpatient settings when referral to a hospital was not possible: Results from randomized trials in Africa.

INTRODUCTION: Serious bacterial neonatal infections are a major cause of global neonatal mortality. While hospitalized treatment is recommended, families cannot access inpatient treatment in low resource settings. Two parallel randomized control trials were conducted at five sites in three countries (Democratic Republic of Congo, Kenya, and Nigeria) to compare the effectiveness of treatment with experimental regimens requiring fewer injections with a reference regimen A (injection gentamicin plus injection procaine penicillin both once daily for 7 days) on the outpatient basis provided to young infants (0-59 days) with signs of possible serious bacterial infection (PSBI) when the referral was not feasible. Costs were estimated to quantify the financial implications of scaleup, and cost-effectiveness of these regimens. METHODS: Direct economic costs (including personnel, drugs and consumable costs) were estimated for identification, prenatal and postnatal visits, assessment, classification, treatment and follow-up. Data on time spent by providers on each activity was collected from 83% of providers. Indirect marginal financial costs were estimated for non-consumables/capital, training, transport, communication, administration and supervision by considering only a share of the total research and health system costs considered important for the program. Total economic costs (direct plus indirect) per young infant treated were estimated based on 39% of young infants enrolled in the trial during 2012 and the number of days each treated during one year. The incremental cost-effectiveness ratio was calculated using treatment failure after one week as the outcome indicator. Experimental regimens were compared to the reference regimen and pairwise comparisons were also made. RESULTS: The average costs of treating a young infant with clinical severe infection (a sub-category of PSBI) in 2012 was lowest with regimen D (injection gentamicin once daily for 2 days plus oral amoxicillin twice daily for 7 days) at US$ 20.9 (95% CI US$ 16.4-25.3) or US$ 32.5 (2018 prices). While all experimental regimens B (injection gentamicin once daily plus oral amoxicillin twice daily, both for 7 days), regimen C (once daily of injection gentamicin injection plus injection procaine penicillin for 2 days, thereafter oral amoxicillin twice daily for 5 days) and regimen D were found to be more cost-effective as compared with the reference regimen A; pairwise comparison showed regimen D was more cost-effective than B or C. For fast breathing, the average cost of treatment with regimen E (oral amoxicillin twice daily for 7 days) at US$ 18.3 (95% CI US$ 13.4-23.3) or US$ 29.0 (2018 prices) was more cost-effective than regimen A. Indirect costs were 32% of the total treatment costs. CONCLUSION: Scaling up of outpatient treatment for PSBI when the referral is not feasible with fewer injections and oral antibiotics is cost-effective for young infants and can lead to increased access to treatment resulting in potential reductions in neonatal mortality. CLINICAL TRIAL REGISTRATION: The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

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.

Extended-interval gentamicin administration in neonates: a simplified approach.

OBJECTIVE: Gentamicin dosing is highly variable and remains complicated in the neonatal population. Traditional dosing in our unit resulted in an excessive number of elevated trough serum gentamicin levels. We hypothesized that one uniform gentamicin dose for neonates of all gestational ages will reduce the incidence of elevated trough levels from 50 to 10%. STUDY DESIGN: Our prospective, randomized, controlled trial enrolled eligible neonates into two groups, according to gestational age (⩽34 6/7 (group I) and >35 0/7 weeks (group II)). Patients in the study arm received a dose of gentamicin 5 mg kg(-1) intravenous (i.v.) every 36 h, whereas patients in the control arm received traditional dosage. Patients were monitored for resolution of infection, serum gentamicin levels and adverse effects. We confirmed our findings in a follow-up study. Fisher's exact and Mann-Whitney tests were used for statistical analysis. RESULTS: We enrolled 96 neonates, 50 in group I (n=25 per arm) and 46 in group II (n=23 per arm). Elevated trough levels were reduced by 66% in group I (P=0.61) and 100% in group II (P=0.0015). In the study arm of both groups, 48/49 neonates had Cmin serum gentamicin concentration (SGC) <2 mg l(-1) and the majority had a trough SGC <1 mg l(-1) (P<0.0001). The study dose resulted in maximum gentamicin levels in the goal range and a 50% reduction in dosage modifications. There were no treatment failures or adverse effects. Our follow-up study phase confirmed these results. CONCLUSION: A standardized gentamicin dosage of 5 mg kg(-1) i.v. every 36 h to neonates of all gestational ages was safe and resulted in SGCs in goal therapeutic ranges. The implications of this simplified gentamicin dosage are to reduce health-care costs by less frequent dosing of gentamicin and reducing medication errors in physician prescribing from complicated dosing schemes.

Cost analysis of gentamicin-impregnated collagen sponges in preventing sternal wound infection post cardiac surgery.

OBJECTIVE: The use of antibiotic-impregnated sponges (Collatamp) during cardiac surgery is controversial. We analysed the cost-effectiveness of its selective use in patients at high-risk of sternal wound infection (SWI). METHOD: Postoperative costs were analysed in two groups of patients undergoing heart surgery between 2011 and 2013: those with SWI (group 1) and in high-risk patients without SWI (group 2). The potential cost of gentamicin-impregnated collagen sponges (GCS) use in high-risk patients was compared with our current practice. RESULTS: We identified 1,251 patients with at least one recognised risk factor for developing SWI in this period. Of these, 18 developed SWI (incidence 1.4%). The median postoperative cost per patient without SWI was £9,617. The additional cost per patient incurred by SWI was £4,860.75. The annual additional cost for treating patients with SWI was £43,749. With a 50% reduction in SWI, the annual additional cost of treating these patients would be reduced to £21,873. The cost of GCS is £80 per patient. Adding this to £21,873 gives a potential total cost of £71,913 in the treated high-risk cohort. CONCLUSION: In our practice the annual cost of treating SWI in high-risk patients without use of GCS is lower than the annual cost of using GCS in all high-risk patients (£43,749 versus £71,913) if it produces a 50% reduction in SWI. The reduction in the incidence of SWI poses no economic benefit when the cost of the product is factored in.

Comparing a combination of penicillin G and gentamicin to a combination of clindamycin and amikacin as prophylactic antibiotic regimens in prevention of clean contaminated wound infections in cancer surgery.

BACKGROUND AND AIM: Appropriate antibiotic selection and timing of administration for prophylaxis are crucial to reduce the likelihood of surgical site infection (SSI) after a clean contaminated cancer surgery. Our aim is to compare the use of two prophylactic antibiotic (PA) regimens as regards efficacy, timing, and cost. PATIENTS AND METHODS: Two hundred patients with gastric, bladder, or colorectal cancer were randomized to receive preoperative PA, group A received penicillin G sodium and gentamicin and group B received clindamycin and amikacin intravenously. The demographic data of patients were collected, and they were observed for wound infections. RESULTS: Infected wounds occurred in 19 patients with a rate of 9.5%. Highest incidence of SSI was among bladder cancer patients (14.2%); p=0.044. The rate of SSI was 11% in group A, and 8% in group B, p=0.469. The cost of PA administered in group A was significantly less than that of group B (21.96±3.22LE versus 117.05±12.74LE, respectively; p<0.001). SSI tended to be higher among those who had longer time for antibiotic and incision (≥30min) than those who had shorter time interval (<30min), (13% vs. 6.5%, respectively). CONCLUSION: Both penicillin+gentamicin and clindamycin+amikacin are safe and effective for the prevention of SSI in clean contaminated operative procedures. In a resource limited hospital, a regimen including penicillin+gentamicin is a cost-effective alternative for the more expensive and broader coverage of clindamycin+amikacin. Timing of PA is effective in preventing SSIs when administered 30min before the start of surgery.

Cost effectiveness of three drugs for the treatment of S. aureus infections in Nigeria.

BACKGROUND: Resistance of microorganisms to existing antimicrobial agents threatens the effective utilization of available resources in sub-Saharan Africa. Cost-effective utilization of antibacterial agents is essential in effective health care delivery in Nigeria. OBJECTIVES: To determine the most cost effective antibacterial agent in the treatment of S. aureus infections in Lagos metropolis. SETTING: The study was carried out in a teaching hospital, a specialist hospital, a referral center and two private hospitals. METHODS: Cost effectiveness analysis of ciprofloxacin, cefuroxime and gentamicin identified to be most effective agent against 463 clinical isolates of S. aureus obtained from the five hospitals was carried out on the basis of societal, health care and third party perspectives using 'decision table" as an analytical model. Criteria considered in the model included degree of efficacy of the agents, adherence tendencies and tolerability. Both direct (cost of drugs, diagnosis/monitoring, personnel and transportation) and indirect (loss of productivity) costs were evaluated. MAIN OUTCOME MEASURES: These include economic outcome as total therapy cost, clinical outcomes as extent of antibacterial effectiveness obtained from degree of antibacterial efficacy, a proxy measurement of cure rates, and adherence tendency. Humanistic outcome was also measured as tolerability prorated from literature reported degree of adverse drug reactions events, risk of infection and pains from drug administration. RESULTS: Ciprofloxacin tablet is a dominant option and much more cost-effective than either cefuroxime or gentamicin in the treatment of S. aureus in Lagos. Regardless of the perspective of analysis, ciprofloxacin has the least cost effectiveness ratio of NGN4214.66 ($28.09), NGN2392.63 ($16.00) and NGN2048.66 ($13.65) from societal, health care and third party payer perspectives, respectively. Sensitivity analysis by increasing the effectiveness index of gentamicin injection-the least cost effective option to the value for the most cost effective option did not change the results. CONCLUSION: Ciprofloxacin should be used as first-line-treatment of S aureus in Lagos as it will lead to significant cost savings in the treatment of S. aureus infections.

Ertapenem compared to combination drug therapy for the treatment of postpartum endometritis after cesarean delivery.

OBJECTIVE: Ertapenem is a broad spectrum carbapenem approved for the treatment of postpartum endometritis. Data regarding clinical outcomes after treatment with ertapenem for endometritis after cesarean delivery are limited. Our objectives were to compare clinical outcomes and cost of ertapenem versus a multi-drug regimen for treatment of endometritis after cesarean delivery. METHODS: Retrospectively, patients with endometritis after cesarean delivery who were treated with ertapenem (group A) were compared to those treated with a combination regimen (group B). Mann-Whitney U and Fisher's Exact were used for statistical analysis with p value <0.05 considered statistically significant. RESULTS: Sixty-three patients were included: 31 in group A and 32 in group B. Demographics and intrapartum characteristics did not differ. Number of administered doses (A: 3, B: 11.5 p < 0.0001), cost (A: $156.63, B: $54.48 p < 0.0001) and nursing time in minutes (A: 6.6, B: 25.3 p < 0.0001) were different between both groups. Wound complications were higher in group A, occurring in 7 patients compared to 1 patient in group B (p = 0.024). CONCLUSION: Although time and number of administered doses were less in group A, given the high wound complication rate in patients treated with ertapenem, this drug may not be appropriate for all patients with endometritis after CD.

Cost-Effectiveness of daptomycin versus vancomycin and gentamicin for patients with methicillin-resistant Staphylococcus aureus bacteremia and/or endocarditis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an increasingly common cause of bacteremia and endocarditis. The cost-effectiveness (CE) of daptomycin was compared with that of vancomycin-gentamicin in patients with MRSA bacteremia with or without endocarditis. METHODS: With use of data from an open-label, randomized study comparing daptomycin with vancomycin-gentamicin in the aforementioned patient population, 3 cost strata were considered: (1) study drug acquisition (daptomycin, $0.37/mg; vancomycin, $7/g; and gentamicin, $0.12/mg); (2) stratum 1 plus the cost of therapy for treatment failures and adverse events, therapeutic drug monitoring, and preparation and administration of all medications; and (3) stratum 2 plus hospital bed costs. Drug costs were based on mean wholesale price, with other costs based on those for a typical community hospital. Cost-effectiveness ratios were calculated as cost divided by proportion of successes. Sensitivity analyses were performed by varying the study drug cost. RESULTS: Forty-five (20 successes) and 44 (14 successes) patients received daptomycin and vancomycin-gentamicin, respectively. The respective median cost-effectiveness ratios for daptomycin and vancomycin-gentamicin for each cost stratum were as follows: $4082 (range, $1062-$13,893) and $560 (range, $66-$1649) for stratum 1 (P < .001); $4582 (range, $1109-$21,882) and $1635 (range, $163-$33,444) for stratum 2 (P = .026); $23,639 (range, $6225-$141,132) and $26,073 (range, $5349-$187,287) for stratum 3 (P = .82). Sensitivity analyses indicated that if the cost of vancomycin was $0, strata 3 cost-effectiveness ratios did not differ ($23,639 and $25,668, respectively; P = .85). Similar results between groups were seen among patients with bacteremia. CONCLUSIONS: When all costs of therapy were considered, the cost-effectiveness of daptomycin and vancomycin-gentamicin was similar, even if the cost of vancomycin was $0.

Liquid gentamicin and vancomycin in bone cement: a potentially more cost-effective regimen.

This study investigated the use of liquid gentamicin, a much less costly antibiotic (<1/20 the price of tobramycin) with a broad antimicrobial spectrum, alone and in combination with vancomycin in bone cement. Standardized cement specimens loaded with 480 mg of liquid gentamicin, 4 g of powdered vancomycin, or both antibiotics were tested for elution characteristics, bioactivity, compressive strength, and porosity. Vancomycin elution was enhanced by 146% with the addition of gentamicin liquid, and gentamicin elution was enhanced by 45% when combined with vancomycin. Bioassay confirmed the bactericidal activity of the released antibiotics. Adding liquid gentamicin increased porosity, whereas adding vancomycin did not. Compressive strength decreased by 13%, 37%, and 45% in specimens containing vancomycin, liquid gentamicin, and both antibiotics, respectively. Despite inferior mechanical properties, the temporary nature of cement beads and spacers makes the liquid gentamicin-vancomycin mixture a potentially more cost-effective regimen in bone cement to treat musculoskeletal infections.

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.

Mastite subclínica causada por Staphylococcus aureus: custo-benefício da antibioticoterapia de vacas em lactação / Subclinical mastitis caused by Staphylococcus aureus: cost benefit analysis of antibiotic therapy in lactating cows

Avaliou-se a relação custo-benefício do tratamento da mastite subclínica bovina causada por Staphylococcus aureus. Foram selecionados 270 quartos mamários com mastite subclínica e sadios, divididos em quatro grupos de acordo com o estádio de lactação e o tratamento. O grupo 1 foi formado por animais entre 10 e 60 dias da lactação e tratados contra mastites; o grupo 2 incluiu animais entre 61 dias da lactação e dois meses antes da secagem e tratados contra mastite; o grupo 3 foi formado por animais entre 10 e 60 dias da lactação, não tratados contra mastite; e o grupo 4 foi formado por animais entre 61 dias em lactação e dois meses antes da secagem, não tratados. O tratamento foi realizado pela infusão intramamária de 150mg de gentamicina, uma vez ao dia. A reavaliação foi efetuada após 30 dias. Para os cálculos dos custos com o tratamento, foram considerados uma prevalência de S. aureus de 5 por cento e os gastos com medicamento, descarte do leite, antibiograma e mão-de-obra. Observou-se redução de 2 por cento e 14 por cento das receitas nos grupos 1 e 2, respectivamente, quando comparada com as receitas obtidas antes do tratamento, demonstrando ser economicamente inviável o tratamento da mastite subclínica bovina causada por S. aureus, durante a lactação.

Economic evaluation of the treatment bovine subclinical mastitis caused by S. aureus was evaluated. Two hundred and seventy udder quarters with or without subclinical mastitis were distributed into four groups, in conformity to lactational stage and treatments. Group 1 included animals treated between 10 and 60 days of lactation; group 2 included animals treated from 61 days of lactation to two months before drying; group 3 included animals no treated between 10 and 60 days of lactation; group 4 included animals no treated from 61 days of lactation to two months before drying. Treatment with gentamicin (150mg) was accomplished by intramammary doses, once a day, after performing sensitivity tests. The mammary quarters were re-evaluated after 30 days. The costs with the treatment were calculated considering a S. aureus prevalence of 5 percent as well as expenses with antibiotic, milk disposal, tests of drug sensitivity and workload. There was loss of income of 2 percent and 14 percent in the groups 1 and 2, respectively, when compared with the values before the treatment. In such case, the treatment of bovine subclinical mastitis caused by S. aureus in the lactation was economically unviable.

Cost effectiveness of local collagen-gentamicin as prophylaxis for sternal wound infections in different risk groups.

OBJECTIVES: In a randomized trial addition of local collagen-gentamicin in the sternal wound reduced the rate of sternal wound infection (SWI) to about 50% compared to intravenous prophylaxis alone. The aim of the present study was to evaluate the economic rationale for its use in every-day clinical practice. This includes the question whether high-risk groups that may have particular benefit should be identified. DESIGN: For each patient with SWI in the trial the costs attributable to the SWI were calculated. Risk factors for SWI were identified and any heterogeneity of the effect of the prophylaxis examined. RESULTS: The mean cost of a SWI was about 14500 Euros. A cost effectiveness analysis showed that the prophylaxis was cost saving. The positive net balance was even higher in risk groups. Assignment to the control group, overweight, diabetes, younger age, mammarian artery use, left ventricular ejection fraction <35% and longer operation time were independent risk factors for infection. CONCLUSION: The addition of local collagen-gentamicin to intravenous antibiotic prophylaxis was dominant, i.e. resulted in both lower costs and fewer wound infections.

A clinical and economic study of community-acquired pneumonia between single versus combination therapy.

BACKGROUND: Pneumonia is one of the leading causes of morbidity and mortality among children in many developing countries. It is reported that 12.9 million children under 5 years of age died world-wide in 1990 and one-third of these deaths or 4.3 million annually were attributed to acute respiratory infection with pneumonia. OBJECTIVES: On this basis, a study was conducted in a district hospital to study the therapy outcomes of antibiotic regimens used in pediatric community-acquired pneumonia (CAP) management and to conduct a cost-effectiveness analysis (CE) between IV ampicillin versus combination therapy of IV ampicillin and IV gentamicin. METHOD: A prospective, randomized, controlled, single blind study was conducted in a pediatric ward in a 80-bed district hospital. Pediatric patients diagnosed with CAP aged 2 months to 5 years old were randomly and equally divided into two treatment arms: ampicillin versus ampicillin plus gentamicin. The dose of IV ampicillin used in this study was 100 mg/kg/day divided every 6 h and 5 mg/kg of IV gentamicin as a single daily dose. Both clinical and economic evaluations were carried out to compare both treatment arms. RESULTS: With the inclusion and exclusion criteria, only 40 patients diagnosed with CAP were included in the study. The results showed that the two treatment arms were significantly different (P < 0.05) in terms of duration of patients on ampicillin, number of days of hospitalization and time to switch to oral therapy. A significant difference was noted between the two treatment modalities in terms of effectiveness and cost (P < 0.05). CONCLUSION: Overall, the endpoint of this study showed that the total cost per patient of ampicillin-treated group is cheaper than the total cost with the combination therapy (ampicillin plus gentamicin) and reduced unnecessary exposure to adverse effects or toxicities. Besides that, addition of gentamicin in the treatment modalities will only increase the cost of treatment without introducing any changes in the treatment outcome.

Liquid gentamicin in bone cement: a laboratory study of a potentially more cost-effective cement spacer.

BACKGROUND: Liquid gentamicin is approved by the Food and Drug Administration, is readily available, and is much less costly than tobramycin, the more commonly used antibiotic in cement spacers. The purpose of the present study was to test the mechanical properties, elution characteristics, and antibacterial activity of liquid gentamicin in an acrylic bone cement spacer. METHODS: Standardized specimens consisting of Palacos cement combined with liquid gentamicin, powdered tobramycin, or no antibiotic were fashioned, and the three groups were tested with regard to compressive and tensile strength, elution characteristics (with use of radioimmunoassays), and antibacterial activity (with use of bioassays). RESULTS: The ultimate compression strength decreased by 49% (from 64.65 +/- 3.89 MPa to 32.96 +/- 3.33 MPa) and the ultimate tension strength decreased by 46% (from 35.85 +/- 2.97 MPa to 19.20 +/- 0.36 MPa) when the specimens containing 480 mg of liquid gentamicin were compared with the controls. The addition of tobramycin had no significant effect compared with the controls. The majority of gentamicin was released from the cement during the initial twenty-four hours (mean concentration, 26.4 mcg/mL). The mean concentrations at three and six weeks were 4.15 and 0.65 mcg/mL, respectively. The bioassays confirmed the bactericidal activity of the gentamicin released from the cement. CONCLUSIONS: Liquid gentamicin in bone cement is potent and bactericidal. Although the mechanical properties of the cement are significantly diminished by the addition of liquid gentamicin, the temporary nature of the cement spacer makes its use potentially worthwhile given the substantial cost savings to the hospital and the patient.

Choice of antibiotics for infection prophylaxis in emergency cesarean sections in low-income countries: a cost-benefit study in Mozambique.

BACKGROUND: There is a need to assess the cost-benefit of different models of antibiotic administration for the prevention of post cesarean infection, particularly in resource-scarce settings. DESIGN: Randomized, nonblinded comparative study of a single combined preoperative dose of gentamicin and metronidazole vs. a post cesarean scheme for infection prophylaxis. METHODS: Pregnant women (n = 288) with indication for emergency cesarean section were randomly allotted to two groups. Group 1 (n = 143) received the single, combined dose of prophylactic antibiotics and group 2 (n = 145) received, over 7 days, the postoperative standard scheme of antibiotics followed in the department. Both groups were followed up during 7 days for detection of signs of wound infection, endometritis, peritonitis and urinary tract infection. MAIN OUTCOME MEASURES: Prevalence of postoperative infection, mean hospital stay and costs of antibiotics used. RESULTS: Women completing the study (n = 241) were distributed into group 1 (n = 116) and group 2 (n = 125). No significant difference was found neither in the prevalence of postoperative infection nor in the mean hospital stay. No death occurred. The cost of the single dose of prophylactic antibiotics was less than one-tenth of the cost of the standard postoperative scheme. CONCLUSION: In our setting, the administration of a single dose of 160 mg of gentamicin in combination with 500 mg of metronidazole before emergency cesarean section for prevention of infection is clinically equivalent to existing conventional week-long postoperative therapy, but at approximately one-tenth of the cost.

Piperacillin-tazobactam is more effective than ceftriaxone plus gentamicin in febrile neutropenic patients with hematological malignancies: a randomized comparison.

GOALS: Efficacy and costs of empirical antibacterial therapy in febrile neutropenic patients are important issues. Several strategies have been reported to be similarly effective: monotherapy with cefepime, ceftazidime or a carbapenem or duotherapy with an antipseudomonal beta-lactam antibiotic or ceftriaxone in combination with an aminoglycoside. Piperacillin-tazobactam monotherapy is promising, but its role in this setting still has to be defined. PATIENTS AND METHODS: Of 212 consecutive febrile episodes in 130 neutropenic patients with hematological malignancies randomized to receive either piperacillin-tazobactam (4.5 g every 8 h; group A) or ceftriaxone (2 g once daily plus gentamicin 5 mg/kg once daily; group B), 183 episodes (98 group A, 85 group B) were evaluable for response. RESULTS: Defervescence within 72 h without modification of the antibiotic therapy was achieved in 56/98 episodes (57.1%) in group A and in 30/85 (35.3%) in group B (P=0.0047). If fever persisted, teicoplanin plus gentamicin (group A) or teicoplanin plus ciprofloxacin (group B) were added. All patients still febrile then received meropenem, teicoplanin and amphotericin B. With these modifications of antibiotic therapy, 89.8% of patients in group A had responded at 21 days but only 71.8% in group B (P=0.005). The mean total antibiotic drug cost in group A was only 39.4% of that in group B (euro 445 versus euro 1129; P=0.010). CONCLUSION: Piperacillin-tazobactam monotherapy is significantly more effective and cost-efficient than ceftriaxone plus gentamicin as first-line therapy in febrile neutropenic patients with hematological malignancies.

[Comparative clinical-economic analysis of antibiotic therapy in pyogenic inflammatory diseases of the lower extremities]. / Sravnitel'nyi kliniko-ékonomicheskii analiz programm antibiotikoterapii gnoino-vospalitel'nykh zabolevanii nizhnikh konechnostei.

A randomized comparative investigation was carried out in two equal groups of patients with pyo-inflammatory diseases of lower extremities (the total number 50 patients) in order to study effectiveness and tolerance to Netilmycin (1st group) and Gentamycin (2nd group) given in combination with Cefasolin. Clinical symptoms were estimated immediately after operation, in 3, 6 and 10-12 days after it. Bacteriological investigations were fulfilled immediately after operation, in 72 h and in 6-10 days after the beginning of antibacterial therapy. Clinical and biochemical investigations of blood were fulfilled before and in 10 days after the beginning of the treatment. Effectiveness of the treatment in the first group was 100%, in the second group--80%. In the second group the antibiotics were changed in 20% of cases and the average duration of hospitalization among the patients of this group was reliably longer that in the first group. The eradication rating of Netilmycin was higher than that of Gentamycin (25 strains from 25 and 20 from 25 respectively). Gentamycin had a pronounced nephrotoxic effect (elevation of the level of creatinin and urea of blood in dynamics by 21% and 32%), as compared with Netilmycin (9% and 3%). Total expenses to antibiotic therapy in the first group made up 97,650 rub, and in the second group 106,245 rub. Netilmycin in combination with Cefasolin was more effective for acute pyo-inflammatory diseases of lower extremities than a combination of Gentamycin with Cefasolin, it more rapidly resulted in reduction of clinical signs of inflammation, was better endured and more economical.

[Health Economical Evaluation of antibiotic prophylaxis against postoperative endophthalmitis]. / Gesundheitsökonomische Bewertung einer antibiotischen Prophylaxe gegenüber postoperativen Endophthalmitiden.

BACKGROUND: Two independent epidemiological studies recently suggested the prophylactic relevance of an intraocular antibiosis against endophthalmitis after cataract surgery. The resulting intervention programme, however, has not only ethical drawbacks, but also has a health economical dimension, which will be focussed in this paper. MATERIAL AND METHODS: A cost analysis is performed to compare the direct costs saved by prevention of endophthalmitis cases and the costs generated by the prophylaxis itself. Furthermore, the clinics' indirect costs due to treatment of unprevented endophthalmitis cases are estimated. RESULTS: The overall gain in direct costs turns out to be about 368 000 Euro p. a., the indirect costs from the clinics' view can be reduced by about 260 000 Euro p. a. due to prevention of endophthalmitis cases by the antibiotic intervention. CONCLUSIONS: From an economical point of view, antibiotic prophylaxis can be suggested; the risk of longitudinally reduced antibiotic effectiveness of the antibiotic agents, however, strongly calls for an overall health political decision rather than for an immediate implementation of the corresponding intervention programme.

A pilot study evaluating the safety and microbiologic efficacy of an economically viable antimicrobial lozenge in patients with head and neck cancer receiving radiation therapy.

BACKGROUND: Mucositis occurs in almost all radiotherapy-treated head and neck cancer patients, in approximately 75% of patients receiving hematopoietic marrow transplantation, and in approximately 40% of all patients who receive chemotherapy. Mucositis is painful, may affect all oral functions, and is a dose- and rate-limiting toxicity of therapy for cancer. Radiation-associated mucositis (onset, intensity, and duration) has been shown in recent clinical trials to be modified by the use of antibacterial/antifungal lozenges. PURPOSE: The aim of this collaborative two-center phase II study was to assess the toxicity and microbiologic efficacy of an economically viable antimicrobial lozenge in the management of patients receiving radiation therapy for head and neck cancer. MATERIALS AND METHODS: Seventeen patients scheduled to receive radical or postoperative radiotherapy were provided with bacitracin, clotrimazole, and gentamicin (BCoG) lozenges (one lozenge dissolved in the mouth qid from day 1 of radiotherapy until completion). Ease of use and palatability of the lozenges, patients' symptoms (swallowing and pain), and quantitative and qualitative microbiologic evaluation of an oral rinse collection was conducted at least once weekly during radiation therapy. RESULTS: No significant side effects were reported from the use of the lozenges. The lozenges were well tolerated at the beginning of treatment by all patients, with some minor difficulty associated with oral discomfort toward the end of the treatment. Microbiologic evaluation showed consistent elimination of yeast organisms in all patients. In four patients there was no growth of gram-negative bacilli on culture, whereas in two patients, fluctuating counts were seen, and one patient had increased counts. The remaining patients had significant reduction in the gram-negative bacilli counts. CONCLUSIONS: This study demonstrated that the BCoG lozenge is tolerable and microbiologically efficacious, achieving elimination of Candida in all patients and reduction in gram-negative flora in most patients. A phase III study is underway to evaluate the clinical efficacy of this lozenge.

Once daily dosing of gentamicin in infants and children.

BACKGROUND: Aminoglycosides are frequently used in children. The standard daily dosing (SDD) in infants and children is twice or three times daily depending on age. The aim of this paper is to review the current data regarding the safety and effectiveness of once daily dosing (ODD) of gentamicin in children. METHODS: A Medline search was conducted for comparison studies between ODD and SDD of gentamicin in children in term of pharmacokinetic indices and toxicity. RESULTS: Overall 13 studies describing ODD of gentamicin in children were found suitable for this review. In most studies steady state peak serum gentamicin concentrations were significantly higher in the ODD groups. Steady state trough concentrations >2 microg/ml were documented in 5 to 55% of patients treated with the SDD as compared with 0 to 24% in the ODD groups. The mode of dosing did not affect the volume of distribution; however, the t1/2 was significantly longer in the ODD groups. ODD was found to be cost-saving. In a few studies the efficacy of ODD was similar to that of SDD. CONCLUSIONS: These studies suggest that ODD compared with SDD of gentamicin is theoretically more efficacious and has no higher toxicity at 48 to 96 h in neonates and at 3 to 10 days of therapy in older infants and children.