Assessment of the In Vitro Cytotoxic Profile of Two Broad-Spectrum Antibiotics-Tetracycline and Ampicillin-On Pharyngeal Carcinoma Cells.

Background and Objectives: In spite of the fact that antibiotics are considered to be the cornerstone of modern medicine, their use in the treatment of cancer remains controversial. In the present study, the main objective was to examine the effects of two antibiotics-tetracycline and ampicillin-on the viability, morphology, migration, and organization and structure of the nuclei and the actin fiber network of pharyngeal carcinoma cells-Detroit-562. Materials and Methods: In order to determine the viability of the cells, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was applied after the cells were stimulated with five concentrations of tetracycline and ampicillin (10, 25, 50, 75, and 100 µM) for 72 h. A scratch assay was used to assess the migration ability of the cells. For the visualization of the nuclei and actin fibers, 4,6-diamidino-2-phenylindole (Dapi) and Rhodamine-Phalloidin were used. Results: There are different effects of tetracycline and ampicillin. Thus, tetracycline: (i) exhibited a concentration-dependent cytotoxic effect, decreasing cell viability to approximately 46%; (ii) inhibits cellular migration up to 16% compared to 60% for control cells; and (iii) induces changes in cell morphology as well as apoptotic changes in the nucleus and F-actin fibers. In contrast, in the case of ampicillin, an increase in viability up to 113% was observed at 10 µM, while a decrease in viability up to approximately 94% was observed at the highest concentration tested (100 µM). Conclusions: The results indicated a different effect regarding the impact on pharyngeal carcinoma cells. Thus, tetracycline has a concentration-dependent cytotoxic effect, while in the case of ampicillin a slight stimulation of cell viability was observed.

Simultaneous pharmacokinetic/pharmacodynamic (PKPD) assessment of ampicillin and gentamicin in the treatment of neonatal sepsis.

OBJECTIVES: This study aimed to simultaneously investigate the pharmacokinetics of ampicillin and gentamicin, currently the WHO standard of care for treating neonatal sepsis. METHODS: Pharmacokinetic data were collected in 59 neonates receiving ampicillin and gentamicin for suspected or proven sepsis in the NeoFosfo trial (NCT03453177). A panel of 23 clinical Escherichia coli isolates from neonates with sepsis, resistant to either ampicillin, gentamicin or both, were tested for susceptibility using chequerboards. Pharmacokinetic/pharmacodynamic (PKPD) modelling and simulations were used to compare single-agent (EUCAST MIC) and combination (chequerboard MIC) target attainment with standard dosing regimens. RESULTS: A model was established that simultaneously estimated parameters of a one-compartment ampicillin model and a two-compartment gentamicin model. A common clearance for both drugs was used (6.89 L/h/70 kg) relating to glomerular filtration (CLGFR), with an additional clearance term added for ampicillin (5.3 L/h/70 kg). Covariate modelling included a priori allometric weight and post-menstrual age scaling of clearance. Further covariate relationships on renal clearance were postnatal age and serum creatinine.Simulation-based PKPD assessments suggest good Gram-positive (MIC ≤ 0.25 mg/L) cover. However, less than one-quarter of neonates were predicted to receive efficacious coverage against Enterobacterales (MIC ≤ 2 mg/L). The benefit of the ampicillin/gentamicin combination was limited, with only 2/23 E. coli clinical strains showing FIC index < 0.5 (synergy) and most in the range 0.5-1 (suggesting additivity). Simulations showed that feasible dosing strategies would be insufficient to cover resistant strains. CONCLUSIONS: PKPD simulations showed ampicillin and gentamicin combination therapy was insufficient to cover Enterobacterales, suggesting the need for alternative empirical treatment options for neonatal sepsis.

Management Patterns in Pediatric Complicated Sinusitis.

OBJECTIVES: Sinusitis is a common pediatric illness that can be complicated by periorbital or intracranial extension. Patients can be managed with antimicrobials alone or in conjunction with surgical intervention. This article examines management patterns and outcomes in pediatric patients presenting with complicated sinusitis. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care pediatric hospital. SUBJECTS AND METHODS: An evaluation of 168 pediatric patients with complicated sinusitis with periorbital complications presenting at a single institution from 2008 to 2018 was performed. Demographics, disease characteristics, in-hospital management, and outcomes were recorded and analyzed. RESULTS: The most common complication was orbital cellulitis, seen in 49% of children. Surgical intervention occurred in 49% of patients, with 36% receiving medical therapy followed by surgery (MTS). Chandler I patients underwent surgical intervention 30% of the time, Chandler II patients 29%, and Chandler III patients 83%. Nineteen percent of initially nonoperative patients started on ampicillin-sulbactam required MTS vs 57% of those started on other antibiotic regimens (P = .01). Twelve percent of initially nonoperative Chandler I to II patients started on ampicillin-sulbactam needed MTS vs 40% started on other antibiotic regimens. Hospital charges for operative patients were $45,056 vs $14,311 for nonoperative patients (P < .01). Hospital charges for patients with surgery followed by medical therapy (SMT) were $45,563 vs $44,393 for MTS (P = .92). CONCLUSION: Nonoperative early stage patients started on ampicillin-sulbactam had a lower risk of MTS. MTS did not cost significantly more than SMT, and there were no significant outcome differences seen.

Informe diário de evidências COVID-19: busca realizada em 20 de maio de 2020 / COVID-19 daily evidence report: search conducted on May 20, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos e 7 protocolos.

Economic comparison of systemic antimicrobial therapies for metritis in dairy cows.

Metritis is a prevalent disease with effects on production, reproduction, and survival, thereby affecting dairy farm profitability. A component of the cost of metritis is antimicrobial therapy. Some antimicrobials result in milk withhold that adds to the cost of disease. The objectives were (1) to determine cost of metritis for 2 antimicrobial treatments using a herd budget that includes costs associated with incidence of concurrent diseases, milk production and reproduction losses, and removal from the herd and (2) to apply sensitivity analysis to determine the cost of different scenarios. Cows with metritis from a previous study assigned randomly to receive ampicillin (AMP, n = 259), an antimicrobial that requires milk withhold, or ceftiofur (CEFT, n = 269), an antimicrobial with no milk withhold, were used for the economic analysis. A group of cows with no metritis (NOMET, n = 268), matched by parity and calving day, served as the baseline for comparison. The incidence of other diseases in the first 60 d postpartum, culling and death, reproductive performance, discarded milk, milk yield, total milk sold per cow, and residual cow value were used as responses. The economic analysis considered the costs associated with therapy, reproductive management, discarded milk, estimated DM consumed, income from saleable milk, and the residual cow value at 300 d postpartum or earlier if the cow was removed from the herd. Sensitivity analyses were performed considering 3 scenarios for milk and feed prices. The incidence of diseases other than metritis (NOMET, 30.4%; AMP, 45.4%; CEFT, 34.0%) and days in the hospital (NOMET, 2.7 d; AMP, 8.6 d; CEFT, 3.5 d) were greater for cows treated with AMP than CEFT. Treatment did not affect the risk of leaving the herd (NOMET, 15.5%; AMP, 15.0%; CEFT, 19.1%). The 21-d pregnancy rate was lower for cows with metritis but did not differ between AMP and CEFT (NOMET, 24.9%; AMP, 18.9%; CEFT, 17.0%). Milk yield was greater for cows without metritis than those with metritis and greater for AMP than CEFT (NOMET, 33.7 kg/d; AMP, 32.5 kg/d; CEFT, 31.2 kg/d). Cost of metritis did not differ with choice of therapy, but it increased as milk price increased. When both milk and feed prices were the average values considered ($0.44/kg and $0.26/kg, respectively), the costs of a case of metritis for AMP and CEFT were, respectively, $344 and $410 when milk was discarded and $267 and $406 when milk was fed to calves. Cost of therapy for AMP and CEFT represented 16.6 and 24.6% of the total cost of metritis when milk was discarded and 21.5 and 24.8% of the total cost of metritis when milk was fed to calves. The largest component of cost of metritis for both therapies was the reduced income from milk minus feed cost, ranging from 40.0 to 56.7%. Collectively, metritis is an expensive disease, and choice of antimicrobial therapy did not influence survival, reproduction, or cost of the disease.

Assessment of inpatient antibiotic use in Halibet National Referral Hospital using WHO indicators: a retrospective study.

OBJECTIVE: Inappropriate use of antibiotics in primary care and hospital settings is a major contributing factor to the spread of antibiotic resistance. Many microorganisms were tested in Eritrea and have proven resistant to ampicillin. The aim of this study was to investigate the prescription pattern, hospital indicator and patient care indicator of antibiotics among hospitalized patients in Halibet National Referral Hospital, Asmara, Eritrea. RESULTS: The data on prescription patterns showed 79% of hospitalizations had at least one antibiotic prescribed and on average 1.29 antibiotics were prescribed per hospitalization; prescribing using generic name was at 97%; all (100%) of the antibiotics were prescribed from the Eritrean National List of Medicines. On average an antibiotic was prescribed for 6.36 days (SD = 6.06). Ampicillin was the most commonly prescribed antibiotic (42.1%) and parenteral was the most common route prescribed (81.4%). The data on hospital indicators showed key antibiotics were out of stock on average for 78.18 days; 87.5% of key antibiotics were available on the day of the study. The data on patient care indicator showed patients taking antibiotics stayed in the hospital for 9.97 days (± 7.33 days).

Assessment of the comparability of CLSI, EUCAST and Stokes antimicrobial susceptibility profiles for Escherichia coli uropathogenic isolates.

BACKGROUND: As many clinical laboratories convert between Stokes, Clinical and Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) methods, the problem of comparing differently derived sets of antimicrobial susceptibility testing (AST) data with each other arises, owing to a scarcity of knowledge of inter-method comparability. The purpose of the current study was to determine the comparability of CLSI, EUCAST and Stokes AST methods for determining susceptibility of uropathogenic Escherichia coli to ampicillin, amoxicillin-clavulanate, trimethoprim, cephradine/cephalexin, ciprofloxacin and nitrofurantoin. METHODS: A total of 100 E. coli isolates were obtained from boric acid urine samples from patients attending GP surgeries. For EUCAST and CLSI, the Kirby-Bauer disc diffusion method was used and results interpreted using the respective breakpoint guidelines. For the Stokes method, direct susceptibility testing was performed on the urine samples. RESULTS: The lowest levels of agreement were for amoxicillin-clavulanate (60%) and ciprofloxacin (89%) between the three AST methods, when using 2017 interpretive guidelines for CLSI and EUCAST. A comparison of EUCAST and CLSI without Stokes showed 82% agreement for amoxicillin-clavulanate and 94% agreement for ciprofloxacin. Discrepancies were compounded by varying breakpoint susceptibility guidelines issued during the period 2011-2017, and through the inclusion of a definition of intermediate susceptibility in some cases. CONCLUSIONS: Our data indicate that the discrepancies generated through using different AST methods and different interpretive guidelines may result in confusion and inaccuracy when prescribing treatment for urinary tract infection.

Antibacterial Susceptibilities of Escherichia coli from Community-Acquired Urinary Tract Infections in the Faroe Islands, Associations with Antibacterial Sales, and Comparison with Iceland and Denmark.

Currently, data on Escherichia coli antibacterial susceptibilities in the Faroe Islands are lacking. The aim was to investigate the antibacterial susceptibilities of E. coli from patients with community-acquired urinary tract infections in the Faroe Islands, correlate with antibacterial sales, and compare with Iceland and Denmark. From 2009 to 2010 and in 2012, 12 general practitioners from the Faroe Islands were recruited to provide urine samples from patients. Antibacterial susceptibilities were determined by disc diffusion testing according to the Clinical and Laboratory Standards Institute methods and criteria. Logistic regression (quasibinomial) of the antibacterial resistance proportions versus mean sales during the period of 2008-2011 was used to determine association. Nonsusceptibility to at least 1 of the 14 antibacterial drugs investigated was found in 54% of the E. coli isolates and was most common to ampicillin (46%), followed by sulfamethoxazole (39%), trimethoprim (27%), trimethoprim/sulfamethoxazole (27%), and <10% to the remaining 10 antibiotics. The resistance prevalence did not change significantly with time. From logistic regression modeling, we find significant associations between antibacterial mean sales and antibacterial resistances. For the resistances in the Faroe Islands compared with data from Denmark and Iceland, we infer two groups of resistances indicating different responses-one steep and one gradual-to antibacterial sales. For these two groups, we find ß1 = 4.77 (Std. Error = 0.624, p-value = 0.002) and ß1 = 0.26 (Std. Error = 0.020, p-value = 4e-7) for the steep and gradual groups, respectively. This knowledge can potentially be used to predict and control the future increase in E. coli resistance with antibacterial sales.

PHARMACOECONOMIC ANALYSIS OF EFFICACY OF DIFFERENT MODES OF ANTIBIOTIC PROPHYLAXIS IN CHOLECYSTECTOMY.

Pharmacoeconomic assessment of efficacy of different modes of antibiotic prophylaxis was made in 27 patients with diagnosis of acute calculous cholecystitis using method of «cost-efficacy¼. Patients have taken ampicillin/sulbactam intravenously in the dose of 1,5 g or cephazolin intravenously in the dose 2,0 g. Medicine should be taken in 30 min. before the operation. The most expensive was antibiotic prophylaxis by cephazolin. The coefficient of «cost-efficacy¼ was 774,2 rubles on 1 unit of efficacy in case of cephazolin and it was 506,1 rubles on 1 unit of efficacy in other group with antibiotic prophylaxis by ampicillin/sulbactam. The authors noted the economical and clinical advantage of antibiotic prophylaxis by ampicillin /sulbactam.

Clinical response at Day 3 of therapy and economic outcomes in hospitalized patients with acute bacterial skin and skin structure infection (ABSSSI).

OBJECTIVE: The FDA recently issued guidance for the types of infections that should be included in trials to support an indication for antibacterial treatment. The latest FDA guidance recommends assessing response to drug therapy at 48 to 72 hours as the primary endpoint in clinical trials. This study evaluated clinical and economic outcomes among acute bacterial skin and skin structure infections (ABSSSI) patients hospitalized at a 3000-bed healthcare system in New Jersey. RESEARCH DESIGN AND METHODS: In this retrospective cohort analysis, adult ABSSSI patients hospitalized between July 2010 and December 2011 were stratified based on infection type: cellulitis/erysipelas and major cutaneous abscess, wound infection, and all ABSSSI. Initial antibiotic therapy was assessed by individual agent, regimen, and MRSA coverage. Day 3 response to initial antibiotic therapy was evaluated based on temperature and lesion cessation outcomes; clinical response rates were assessed by initial therapy and pathogen for each cohort. The impact of response on length of stay (LOS), cost of care, and antibiotic treatment duration were also evaluated. RESULTS: Commonly used antibiotics included vancomycin, cefazolin, piperacillin-tazobactam, and ampicillin-sulbactam; over 40% of patients received empiric therapy with activity against MRSA. Clinical non-response to initial antimicrobial therapy at Day 3 was 39.9%, 30.3%, and 60.7%, for all ABSSSI, cellulitis/abscess, and wound infection patients, respectively. The cost of care among non-responders was over 1.5 times that of responders (p < 0.0001). Non-response to initial therapy was associated with a 3.7 day increase in duration of antibiotic treatment (p < 0.0001). CONCLUSIONS: Results of this study demonstrate that a significant percentage of ABSSSI patients, particularly those with wound infection, were not achieving clinical response at Day 3 of therapy. Failure to respond to drug therapy is associated with substantial increases in LOS, antibiotic treatment duration, and cost of care. LIMITATIONS: This had the inherent limitations associated with a retrospective chart review; because data was initially collected for clinical rather than research purposes, certain information may have been absent, incomplete, or missed by data abstractors.

Efficacy of prophylactic antibiotic administration for breast cancer surgery in overweight or obese patients: a randomized controlled trial.

OBJECTIVE: To assess the impact of prophylactic antibiotics on the prevention of surgical site infection (SSI) and the cost-effectiveness of this prophylaxis for breast cancer surgery in overweight or obese women. BACKGROUND DATA: SSI is higher than expected after breast surgery. Obesity was found to be one of the risk factors. METHODS: The trial was designed as a phase IV randomized, controlled, parallel-group efficacy trial. It was conducted at a tertiary university hospital. Overweight or obese women with clinically early-stage breast cancer who had been assigned to undergo surgery were eligible. Patients were randomly allocated to either a prophylaxis or a control group by using a computer-generated list. The prophylaxis group received 1 g ampicillin-sulbactam intravenously at anesthesia. The control group received no intervention. Patients and observers were blinded to the assignments. The primary outcome was the comparison of SSI incidences of the 2 groups. Patients were monitored for 30 days. RESULTS: A total of 369 patients were included in final analysis, out of which 187 were allocated for prophylaxis and 182 were randomly assigned to the control group. Analysis was done according to the intention-to-treat principle. Prophylaxis significantly reduced the SSI rate (4.8%) in the prophylaxis group when compared with that in the control group [13.7%; relative risk (RR) 0.35; 95% CI: 0.17-0.73]. No adverse reaction was observed. The mean SSI-related cost (20.26 USD) was found to be significantly higher in the control group when compared with that (8.48 USD) in the prophylaxis group. CONCLUSION: Antibiotic prophylaxis significantly decreased SSI incidence after elective surgery and was shown to be cost-effective in obese breast cancer patients. ClinicalTrials.gov Identifier: NCT00356148.

[Cost of therapeutic failure of ampicillin plus amikacin in the treatment of early neonatal sepsis]. / Costo económico marginal del fracaso terapéutico con ampicilina más amikacina en el tratamiento de la sepsis neonatal temprana.

OBJECTIVE: To evaluate the marginal cost of therapeutic failure with Ampicillin/amikacin as the first-line antibiotic treatment of early-onset neonatal sepsis (ENS). METHODS: Out of a total of 121 newborns, 86 failed to respond to Ampicillin/amikacin when it was used as first-line treatment within their first 72h of life. All of them were admitted to the NICU between 2001 and 2005 with suspicion of sepsis. After this failure to respond, vancomycin and/or cefotaxime were used as the second treatment option for these newborns. Using a full cost method we performed a cost analysis with an activity-based-costing (ABC) perspective, identifying the costs generated by these 86 patients. RESULTS: The costs comprising medication, hospitalization, supplies and clinical staff salaries were higher when vancomycin and/or cefotaxime were used (350,924 dollars or 275,116 euros) compared to those generated with an Ampicillin/amikacin regimen (159,251 dollars or 124,878 euros). When compared as protective factors, the relative risk was 1.09 (95% CI; 0.39-2.1 P=0.8) for Ampicillin/amikacin vs. 0.02 (95% CI; 0.04-0.32 P<0.05) for vancomycin and/or cefotaxime. CONCLUSIONS: Even though vancomycin and/or cefotaxime are initially more costly, there is a cost saving derived from the use of this antibiotic treatment as the first-line therapeutic option instead of as a rescue therapy when a lower-efficacy regimen (Ampicillin/amikacin) has failed.

Management and prevention of diabetic foot ulcers and infections: a health economic review.

Diabetic foot ulcers and infections are common and incur substantial economic burden for society, patients and families. We performed a comprehensive review, on a number of databases, of health economic evaluations of a variety of different prevention, diagnostic and treatment strategies in the area of diabetic foot ulcers and infections. We included English-language, peer-reviewed, cost-effectiveness, cost-minimization, cost-utility and cost-benefit studies that evaluated a treatment modality against placebo or comparator (i.e. drug, standard of care), regardless of year. Differences were settled through consensus. The search resulted in 1885 potential citations, of which 20 studies were retained for analysis (3 cost minimization, 13 cost effectiveness and 4 cost utility). Quality scores of studies ranged from 70.8% (fair) to 87.5% (good); mean = 78.4% +/- 5.33%.In diagnosing osteomyelitis in patients with diabetic foot infection, magnetic resonance imaging (MRI) showed 82% sensitivity and 80% specificity. MRI cost less than 3-phase bone scanning + Indium (In)-111/Gallium (Ga)-67; however, when compared with prolonged antibacterials, MRI cost $US120 (year 1993 value) more without additional quality-adjusted life-expectancy. Prevention strategies improved life expectancy and QALYs and reduced foot ulcer rates and amputations.Ampicillin/sulbactam and imipenem/cilastatin were both 80% successful in treating diabetic foot infections but the latter cost $US2924 more (year 1994 value). Linezolid cure rates were higher (97.7%) than vancomycin (86.0%) and cost $US873 less (year 2004 value). Ertapenem costs were significantly lower than piperacillin/tazobactam ($US356 vs $US503, respectively; year 2005 values). Becaplermin plus good wound care may be cost effective in specific populations. Bioengineered living-skin equivalents increased ulcer-free months and ulcers healed, but costs varied between countries. Promogran produced more ulcer-free months than wound care alone (3.75 vs 3.41 months, respectively). Treatment with cadexomer iodine resulted in higher rates of healed ulcer (29% vs 11%) and lower weekly treatment costs (Swedish krona [SEK]903 vs SEK1421; year 1993 values) than standard care. Filgrastim decreased hospital stays, time to resolution and costs (36% lower) compared with usual care. Adjunctive hyperbaric oxygen produced an incremental cost per QALY at year 1 of $US27 310 and $US2255 at year 12 (year 2001 values).Overall, preventive strategies were shown to be cost effective and potentially cost saving. Various antibacterial regimens are cost effective but empiric choices should be based on local resistance patterns. MRI was cost effective compared with three-phase bone scanning + In-111/Ga-67 but not against prolonged antibacterial therapy. Other innovations (becaplermin, bioengineered living-skin equivalents, filgrastim, cadexomer iodine ointment, hyperbaric oxygen, Promogran may be cost effective in this population but more studies are needed to confirm these findings.

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.

A trial of preventing early- and late-onset Group B streptococcal sepsis with combined intrapartum chemoprophylaxis and universal neonatal screening.

BACKGROUND: Prevention of early-onset Group B Streptococcal (GBS) infection has been attempted by employing universal maternal screening for GBS, intrapartum chemoprophylaxis, and a single dose of penicillin given to neonates in the first hour of life. This strategy, however, does not seem to prevent the occurrence of late-onset neonatal group B streptococcal disease. STUDY DESIGN: We assessed early and late-onset GBS disease with the use of a before-after study designed to evaluate the implementation of intrapartum antimicrobial prophylaxis. Moreover, universal neonatal screening for colonization of GBS was carried out with swabs of the external ear canal. Newborns with GBS colonization received a preventive treatment with oral amoxicillin for 10 days. RESULTS: Early-onset GBS infection decreased from 0.5 per thousand at baseline period to 0.19 per thousand at the study period. The incidence of late-onset GBS disease decreased from 1:1348 (0.74 per thousand) to 1:20,710 (0.048 per thousand). The overall cost for universal neonatal screening paid for by the Italian Health System in the study period was 31,065 US dollars with an antibiotic prophylaxis cost of 2,399 US dollars. CONCLUSIONS: A combined strategy based on GBS culture screening and assessment of risk factors for perinatal GBS disease can significantly reduce the rate of both early and late-onset GBS infections.

A series of systematic reviews to inform a decision analysis for sampling and treating infected diabetic foot ulcers.

OBJECTIVES: To review systematically the evidence on the performance of diagnostic tests used to identify infection in diabetic foot ulcers (DFUs) and of interventions to treat infected DFUs. To use estimates derived from the systematic reviews to create a decision analytic model in order to identify the most effective method of diagnosing and treating infection and to identify areas of research that would lead to large reductions in clinical uncertainty. DATA SOURCES: Electronic databases covering period from inception of the database to November 2002. REVIEW METHODS: Selected studies were assessed against validated criteria and described in a narrative review. The structure of a decision analytic model was derived for two groups of patients in whom diagnostic tests were likely to be used. RESULTS: Three studies that investigated the performance of diagnostic tests for infection on populations including people with DFUs found that there was no evidence that single items on a clinical examination checklist were reliable in identifying infection in DFUs, that wound swabs perform poorly against wound biopsies, and that semi-quantitative analysis of wound swabs may be a useful alternative to quantitative analysis. However, few people with DFUs were included, so it was not possible to tell whether diagnostic performance differs for DFUs relative to wounds of other aetiologies. Twenty-three studies investigated the effectiveness (n = 23) or cost-effectiveness (n = 2) of antimicrobial agents for DFUs. Eight studied intravenous antibiotics, five oral antibiotics, four different topical agents such as dressings, four subcutaneous granulocyte colony stimulating factor (G-CSF), one evaluated oral and topical Ayurvedic preparations and one compared topical sugar versus antibiotics versus standard care. The majority of trials were underpowered and were too dissimilar to be pooled. There was no strong evidence for recommending any particular antimicrobial agent for the prevention of amputation, resolution of infection or ulcer healing. Topical pexiganan cream may be as effective as oral antibiotic treatment with ofloxacin for the resolution of local infection. Ampicillin and sulbactam were less costly than imipenem and cilastatin, a growth factor (G-CSF) was less costly than standard care and cadexomer iodine dressings may be less costly than daily dressings. A decision analytic model was derived for two groups of people, those for whom diagnostic testing would inform treatment--people with ulcers which do not appear infected but whose ulcer is not progressing despite optimal concurrent treatment--and those in whom a first course of antibiotics (prescribed empirically) have failed. There was insufficient information from the systematic reviews or interviews with experts to populate the model with transition probabilities for the sensitivity and specificity of diagnosis of infection in DFUs. Similarly, there was insufficient information on the probabilities of healing, amputation or death in the intervention studies for the two populations of interest. Therefore, we were unable to run the model to inform the most effective diagnostic and treatment strategy. CONCLUSIONS: The available evidence is too weak to be able to draw reliable implications for practice. This means that, in terms of diagnosis, infection in DFUs cannot be reliably identified using clinical assessment. This has implications for determining which patients need formal diagnostic testing for infection, on whether empirical treatment with antibiotics (before the results of diagnostic tests are available) leads to better outcomes, and on identifying the optimal methods of diagnostic testing. With respect to treatment, it is not known whether treatment with systemic or local antibiotics leads to better outcomes or whether any particular agent is more effective. Limited evidence suggests that both G-CSF and cadexomer iodine dressings may be less expensive than 'standard' care, that ampicillin/sulbactam may be less costly than imipenem/cilastatin, and that an unlicensed cream (pexiganan) may be as effective as oral ofloxacin. Further research is needed to ascertain the characteristics of infection in people with DFUs that influence healing and amputation outcomes, to determine whether detecting infection prior to treatment offers any benefit over empirical therapy, and to establish the most effective and cost-effective methods for detecting infection, as well as the relative effectiveness and cost-effectiveness of antimicrobial interventions for DFU infection.

Pharmaceutical cost comparison analysis of antimicrobial use for surgical prophylaxis on gastrectomy patients in a tertiary care hospital.

The present study investigated the clinical effects and therapeutic cost of cefazolin (CEZ) and ampicillin/sulbactam (SBT/ABPC) compared to analyze cost-effectiveness for surgical prophylaxis in gastric cancer patients. 157 inpatients who underwent surgery for gastric cancer were investigated. There was no difference between the two groups with regard to sex, age, incidence of complication, stage of cancer, operative time and blood loss, length of hospitalization, the appearance of systematic inflammatory responses syndrome and the prophylactic effect of infection. Meanwhile, decision analysis indicated that the anticipated therapeutic cost per patient in CEZ group was less than that of SBT/ABPC group (USD 142.72 and USD 187.17, respectively). In this case, CEZ use was more cost-effective, insofar as only drug cost was considered.

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.