Consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in the community, European Union/European Economic Area, 1997-2017.

OBJECTIVES: Data on consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of main subgroups of tetracyclines, sulphonamides and trimethoprim and other antibacterials. METHODS: For the period 1997-2017, data on consumption of tetracyclines (ATC group J01A), sulphonamides and trimethoprim (ATC group J01E), and other antibacterials (ATC group J01X) in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials was analysed based on ATC-4 subgroups and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in the community expressed in DDD per 1000 inhabitants per day varied considerably between countries. Between 1997 and 2017, consumption of tetracyclines did not change significantly, while its seasonal variation significantly decreased over time. Consumption of sulphonamides and trimethoprim significantly decreased until 2006, and its seasonal variation significantly decreased over time. The consumption of other antibacterials showed no significant change over time or in seasonal variation. CONCLUSIONS: Consumption and composition of tetracyclines, sulphonamides and trimethoprim, and other antibacterials showed wide variations between EU/EEA countries and over time. This represents an opportunity to further reduce consumption of these groups in some countries and improve the quality of their prescription.

A cost-minimization analysis of treatment options for postmenopausal women with dysuria.

BACKGROUND: Empiric therapy for urinary tract infection is difficult in postmenopausal women because of the higher rates of confounding lower urinary tract symptoms and differential resistance profiles of uropathogens in this population. OBJECTIVE: The objective of the study was to determine the least costly strategy for treatment of postmenopausal women with the primary complaint of dysuria. STUDY DESIGN: We performed a cost minimization analysis modeling the following clinical options: (1) empiric antibiotic therapy followed by urine culture, (2) urinalysis with empiric antibiotic therapy only if positive nitrites and leukocyte esterase, or (3) waiting for culture prior to initiating antibiotics. For all strategies we included nitrofurantoin, trimethoprim/sulfamethoxazole, fosfomycin, ciprofloxacin, or cephalexin. Pathogens included Escherichia coli, Enterococcus faecalis, Klebsiella pneumonaie, or Proteus mirabalis. Pathogens, resistance, treatment success, and medication side effects were specific to postmenopausal women. RESULTS: Cost minimization modeling with TreeAge Pro assumed 73.4% of urinary tract infections were caused by Escherichia coli with 24.4% resistance to nitrofurantoin, trimethoprim/sulfamethoxazole. With our assumptions, empiric antibiotics with nitrofurantoin, trimethoprim/sulfamethoxazole was the least costly approach ($89.64/patient), followed by waiting for urine culture ($97.04/patient). Except for empiric antibiotics with fosfomcyin, empiric antibiotics was always less costly than using urinalysis to discriminate antibiotic use. This is due to the cost of urinalysis ($38.23), high rate of both urinary tract infection (91%), and positive urinalysis (69.3%) with dysuria in postmenopausal women and resultant high rate of antibiotic use with or without urinalysis. Options with fosfomycin were the most expensive because of the highest drug costs ($98/dose), and tornado analyses showed fosfomycin cost was the most impactful variable for model outcomes. Sensitivity analyses showed empiric fosfomycin became the least costly option if drug costs were $25.80, a price still more costly than almost all modeled baseline drug costs. This outcome was largely predicated on low resistance to fosfomycin. Conversely, ciprofloxacin was never the least costly option because of higher resistance and side effect cost, even if the drug cost was $0. We modeled 91% positive urine culture rate in postmenopausal women with dysuria; waiting for the urine culture prior to treatment would be the least costly strategy in a population with a predicted positive culture rate of <65%. CONCLUSION: The least costly strategy was empiric antibiotics with nitrofurantoin and trimethoprim/sulfamethoxazole, followed by waiting on culture results. Local resistance patterns will have an impact on cost minimization strategies. Empiric fosfomycin would be least costly with reduced drug costs, even at a level at which drug costs were higher than almost all other antibiotics. In a population with high posttest probability of positive urine culture, urinalysis adds unnecessary cost. Antibiotic stewardship programs should continue efforts to decrease fluoroquinolone use because of high resistance, side effects, and increased cost.

Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT.

BACKGROUND: People carrying out clean intermittent self-catheterisation (CISC) to empty their bladder often suffer repeated urinary tract infections (UTIs). Continuous once-daily, low-dose antibiotic treatment (antibiotic prophylaxis) is commonly advised but knowledge of its effectiveness is lacking. OBJECTIVE: To assess the benefit, harms and cost-effectiveness of antibiotic prophylaxis to prevent UTIs in people who perform CISC. DESIGN: Parallel-group, open-label, patient-randomised 12-month trial of allocated intervention with 3-monthly follow-up. Outcome assessors were blind to allocation. SETTING: UK NHS, with recruitment of patients from 51 sites. PARTICIPANTS: Four hundred and four adults performing CISC and predicted to continue for ≥ 12 months who had suffered at least two UTIs in the previous year or had been hospitalised for a UTI in the previous year. INTERVENTIONS: A central randomisation system using random block allocation set by an independent statistician allocated participants to the experimental group [once-daily oral antibiotic prophylaxis using either 50 mg of nitrofurantoin, 100 mg of trimethoprim (Kent Pharmaceuticals, Ashford, UK) or 250 mg of cefalexin (Sandoz Ltd, Holzkirchen, Germany); n = 203] or the control group of no prophylaxis (n = 201), both for 12 months. MAIN OUTCOME MEASURES: The primary clinical outcome was relative frequency of symptomatic, antibiotic-treated UTI. Cost-effectiveness was assessed by cost per UTI avoided. The secondary measures were microbiologically proven UTI, antimicrobial resistance, health status and participants' attitudes to antibiotic use. RESULTS: The frequency of symptomatic antibiotic-treated UTI was reduced by 48% using prophylaxis [incidence rate ratio (IRR) 0.52, 95% confidence interval (CI) 0.44 to 0.61; n = 361]. Reduction in microbiologically proven UTI was similar (IRR 0.49, 95% CI 0.39 to 0.60; n = 361). Absolute reduction in UTI episodes over 12 months was from a median (interquartile range) of 2 (1-4) in the no-prophylaxis group (n = 180) to 1 (0-2) in the prophylaxis group (n = 181). The results were unchanged by adjustment for days at risk of UTI and the presence of factors giving higher risk of UTI. Development of antimicrobial resistance was seen more frequently in pathogens isolated from urine and Escherichia coli from perianal swabs in participants allocated to antibiotic prophylaxis. The use of prophylaxis incurred an extra cost of £99 to prevent one UTI (not including costs related to increased antimicrobial resistance). The emotional and practical burden of CISC and UTI influenced well-being, but health status measured over 12 months was similar between groups and did not deteriorate significantly during UTI. Participants were generally unconcerned about using antibiotics, including the possible development of antimicrobial resistance. LIMITATIONS: Lack of blinding may have led participants in each group to use different thresholds to trigger reporting and treatment-seeking for UTI. CONCLUSIONS: The results of this large randomised trial, conducted in accordance with best practice, demonstrate clear benefit for antibiotic prophylaxis in terms of reducing the frequency of UTI for people carrying out CISC. Antibiotic prophylaxis use appears safe for individuals over 12 months, but the emergence of resistant urinary pathogens may prejudice longer-term management of recurrent UTI and is a public health concern. Future work includes longer-term studies of antimicrobial resistance and studies of non-antibiotic preventative strategies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67145101 and EudraCT 2013-002556-32. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 22, No. 24. See the NIHR Journals Library website for further project information.

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.

Antibiotic treatment of urinary tract infection by community pharmacists: a cross-sectional study.

BACKGROUND: Urinary tract infections (UTIs) are one of the most common conditions seen in female patients within primary care. Community pharmacists are familiar with symptomatic UTI management and supplying trimethoprim under patient group direction (PGD) for moderate-to-severe uncomplicated UTIs could improve patient access to treatment. AIM: To compare the care pathway of patients with UTI symptoms attending GP services with those receiving management, including trimethoprim supply under PGD, via community pharmacies. DESIGN AND SETTING: Prospective, cross-sectional, mixed methods approach in 10 community pharmacies within NHS Greater Glasgow and Clyde. METHOD: Pharmacies invited a purposive sample of female patients to participate. Pharmacists had the option of supplying trimethoprim under PGD to patients with moderate-to-severe infection meeting the PGD inclusion criteria. Data from patient (questionnaires and semi-structured telephone interviews) and pharmacist (questionnaires and semi-structured, face-to-face interviews) were quantitatively and qualitatively analysed. RESULTS: Data were recorded on 153 patients, 97 presenting with GP prescriptions and 56 presenting directly in the pharmacy with symptoms suggestive of UTI, of whom 41 received trimethoprim via PGD and 15 received symptomatic management. Both GP adherence to local infection management guidelines and pharmacist application of PGD inclusion/exclusion criteria required improvement. There was demand and support, from patients and pharmacists, for access to antibiotic treatments for UTIs, without prescription, through community pharmacies. CONCLUSION: Operating within PGD controls, antibiotic treatments for UTIs could be provided via community pharmacy to improve patient access to treatment which may also maintain antibiotic stewardship and reduce GP workload.

Antimicrobial prescribing in nursing homes in Finland: results of three point prevalence surveys.

PURPOSE: The purpose of this study was to analyse the Finnish European Surveillance of Antimicrobial Consumption (ESAC) nursing home (NH) point prevalence surveys' (PPSs) data in detail, i.e. to evaluate the variability in the prevalence of antimicrobial prescription between NHs and its relationship to resident characteristics. METHODS: All residents present in NHs for ≥ 24 h and receiving systemic antimicrobials on the day of the survey were included. Data on antimicrobials and their indications (prophylaxis or treatment, type of infection) were collected. RESULTS: Three PPSs were performed: eight NHs participated in April and November 2009 and nine in May-September 2010. In total, there were 5,691 eligible residents (range by survey, 1,706-2,320; range by NH, 60-688), 716 (12.6 %; range by NH, 3.2-33.3 %) of which received at least one antimicrobial and 40 residents received two. The most common indication was prophylaxis (487/5,691, 8.6 %), mainly for urinary tract infection (UTI) (460/487, 94.5 %). Of the residents, 269/5,691 (4.7 %, range by NH, 1.5-6.0 %) were on antimicrobial treatment. UTI (119/269; 44.2 %) was the most common indication for treatment. Methenamine (306/756, 40.5 %) was the most commonly used antimicrobial, followed by trimethoprim (13.6 %) and pivmecillinam (11.0 %). In the eight NHs participating in all three surveys, the prevalence of residents receiving antimicrobials decreased from 16.6 to 9.7 %. CONCLUSIONS: Antimicrobial use was common in NHs in Finland and most were used for UTI prophylaxis and treatment. The usage, however, varied among NHs and tended to decrease during the surveys. NHs may benefit from antimicrobial stewardship interventions focused on UTI.

Prospective blinded laboratory assessment of prophylactic antibiotic compliance in a pediatric outpatient setting.

PURPOSE: Prophylactic antibiotics are commonly used to prevent urinary tract infections in children with conditions such as vesicoureteral reflux. Patient compliance with antibiotics is salient, given the effects that noncompliance can have on development of antibiotic resistance and outcomes of clinical trials. Prior series have shown variable compliance (17% to 70%). However, no study has used objective methods. We hypothesized that direct measurement of urine antibiotic levels can reveal poor compliance. MATERIALS AND METHODS: During a pediatric urology clinic visit patients 0 to 18 years old taking trimethoprim prophylaxis for any urological diagnosis were invited to participate in the study. They were unaware of any potential urine testing before the visit. Urine was sent for chromatography to quantify trimethoprim levels. Parents also completed a compliance self-assessment. RESULTS: Of patients invited to participate 97% consented (54 patients). Of the patients 91% were compliant based on urine levels. Factors not associated with compliance included age, gender, self-report of compliance, duration of time on antibiotics, insurance status and history of breakthrough infection, surgery, pyelonephritis or hospitalization. CONCLUSIONS: This study demonstrates the highest compliance reported for children taking prophylactic antibiotics to prevent urinary tract infection. We attribute this unexpected result to the discussion by specialists of 1 problem for the duration of an office visit. All education in this study was part of clinical care. Thus, our results should be generalizable to nonstudy environments. Future studies should confirm whether this high level of compliance can be achieved by nephrologists and pediatricians. If such compliance cannot be achieved at nonsurgical clinics, then early referral to a pediatric urologist may be warranted.

Inequality in quality? Regional and educational differences in treatment with fluoroquinolone in urinary tract infection of 236,376 Swedish patients.

BACKGROUND: In an international effort to reduce antibiotic resistance, in part suggested to be the effect of inappropriate antibiotic use, several quality indicators for outpatient antibiotic use have been proposed. In this study, geographical and educational differences in fluoroquinolone prescription in the treatment of urinary tract infection in women are presented. METHODS: The age-adjusted ratio of women who were dispensed fluoroquinolones (ciprofloxacin or norfloxacin) among all 236,376 women dispensed any of the following antibiotics used in the treatment of lower urinary tract infection were studied: ciprofloxacin, norfloxacin, pivmecillinam, trimethoprim and nitrofurantoin. Only the first prescription during July 2006 to June 2007 was studied. Prescription data were linked to information on geographical area, marital status, country of birth and educational attainment, which allowed multivariate analysis of the importance of these factors. RESULTS: The rate of fluoroquinolone prescription varied from 29.5% to 17.1% in the 21 regions in Sweden. Middle-aged women with ≥15 years of schooling were more often prescribed fluoroquinolones compared to those with only 9 years (OR 1.28, 95% CI 1.23 to 1.34). CONCLUSION: Quality indicators in healthcare should be developed bearing in mind the overall level of adherence to guidelines and whether there are regional or socioeconomic or other differentials in their distribution in the population because such differentials in healthcare quality might further contribute to inequalities in health.

A multilevel analysis of trimethoprim and ciprofloxacin prescribing and resistance of uropathogenic Escherichia coli in general practice.

OBJECTIVES: A retrospective analysis of databases was performed to describe trimethoprim and ciprofloxacin prescribing and resistance in Escherichia coli within general practices in the West of Ireland from 2004 to 2008. METHODS: Antimicrobial susceptibility testing was performed by disc diffusion methods according to the CLSI methods and criteria on significant E. coli isolates (colony count >10(5) cfu/mL) from urine samples submitted from general practice. Data were collected over a 4.5 year period and aggregated at practice level. Data on antimicrobial prescribing of practices were obtained from the national Irish prescribing database, which accounts for approximately 70% of all medicines prescribed in primary care. A multilevel model (MLwiN) was fitted with trimethoprim/ciprofloxacin resistance rates as outcome and practice prescribing as predictor. Practice and individual routinely collected variables were controlled for in the model. RESULTS: Seventy-two general practices sent between 13 and 720 (median 155) samples that turned out to be E. coli positive. Prescribing at practice level was significantly correlated with the probability of antimicrobial-resistant E. coli with an odds ratio of 1.02 [95% confidence interval (CI) 1.01-1.04] for every additional prescription of trimethoprim per 1000 patients per month in the practice and 1.08 (1.04-1.11) for ciprofloxacin. Age was a significant risk factor in both models. Higher variation between practices was found for ciprofloxacin as well as a yearly increase in resistance. Comparing a 'mean' practice with 1 prescription per month with one with 10 prescriptions per month showed an increase in predicted probability of a resistant E. coli for the 'mean' patient from 23.9% to 27.5% for trimethoprim and from 3.0% to 5.5% for ciprofloxacin. CONCLUSIONS: A higher level of antimicrobial prescribing in a practice is associated with a higher probability of a resistant E. coli for the patient. The variation in antimicrobial resistance levels between practices was relatively higher for ciprofloxacin than for trimethoprim.

Toltrazuril and sulphonamide treatment against naturally Isospora suis infected suckling piglets: is there an actual profit?

A study was carried out to assess the efficacy and the economic profit of prophylactic treatment against Isopsora suis with toltrazuril or with a sulfamethazine/trimethoprim combination in piglets from an intensive pig farm. Thirty-one litters were included in study. Eight litters were treated once with toltrazuril (20 mg/kg b.w.) at 3 days of age (Toltra group); 8 litters were treated with 2 ml/animal of a [corrected] sulphonamide combination (sodium sulfamethazine 250 [DOSAGE ERROR CORRECTED] mg and trimethoprim 50 [DOSAGE ERROR CORRECTED] mg/kg b.w.) for 3 consecutive days starting at 3 days of age (Sulfa group), and 15 litters were untreated (control group). Counts of oocyst per gram on pooled feces sampled from each litter were carried out on Days 7, 14, 21 and 28 and diarrhea was registered daily from pooled samples. Piglets were weighed on Days 1, 7 and 28 and mean weight gain (WG) and daily weight gain (DWG) were evaluated. The economic profit of treatment was evaluated comparing the WG of piglets of each treatment group from the day of birth to Day 28. On Days 14, 21 and 28, toltrazuril showed a better efficacy in controlling fecal oocyst output, diarrhea and weight gain compared with sulphamidic treatment (P<0.001). The budgeting analysis showed a return of economic benefit of euro 0.915 per toltrazuril-treated piglets and an additional cost of euro 1.155 per sulphonamide-treated piglets.

Appropriate antibiotic utilization in seniors prior to hospitalization for community-acquired pneumonia is associated with decreased in-hospital mortality.

BACKGROUND: We analysed the association of mortality and prescription of antibiotics prior to hospitalization for community-acquired pneumonia. METHODS: We used administrative data (hospital abstracts, physician claims, prescriptions) for seniors (age 61 years and over) for Alberta, Canada from 1 April 1994 to 31 March 1999. RESULTS: Hospitalization of 21 191 seniors occurred during the study period. In about 43% of hospitalizations (n = 9034), a physician was consulted prior to hospital admission. Antibiotics were dispensed to 31% of those with a prior physician visit and in about 72%, the antibiotic choice was deemed appropriate. The odds for mortality were significantly decreased in those with prior physician visits (OR = 0.87, P < 0.01), with any antibiotic prescription (OR = 0.66, P < 0.0001), and with an appropriate antibiotic (OR = 0.68, P = 0.03). The choice of an appropriate antibiotic as opposed to an inappropriate antibiotic resulted in a 2.6% absolute and 38% relative mortality reduction. CONCLUSION: Choosing an appropriate outpatient antibiotic in accordance with published expert opinion guidelines compared with inappropriate antibiotic prescriptions decreased hospital mortality in patients subsequently hospitalized for community-acquired pneumonia.

Environmental risk assessment of antibiotics: comparison of mecillinam, trimethoprim and ciprofloxacin.

The effects of mecillinam, trimethoprim and ciprofloxacin, antibiotics used in the treatment of urinary tract infections, on the aquatic environment were assessed. Mecillinam and ciprofloxacin were both readily biodegradable (primary degradation) in activated sludge, whereas trimethoprim persisted. The toxicity of these antibiotics towards sludge bacteria, a green alga, a cyanobacterium, a crustacean and a fish were investigated; both mecillinam and ciprofloxacin were highly toxic to the cyanobacterium Microcystis aeruginosa (EC50 in the range 5-60 microg/L). Risk characterization for the aquatic environment was performed for the three compounds by calculating the predicted environmental concentration (PEC) and the predicted no-effects concentration (PNEC). A PEC/PNEC ratio of <1 indicates that, with the present pattern of use, no environmental risk is expected. PEC/PNEC ratios of <1 for present usage in Europe were found for mecillinam and trimethoprim whereas a PEC/PNEC ratio >1 was found for ciprofloxacin.

Not so simple cystitis: how should prescribers be supported to make informed decisions about the increasing prevalence of infections caused by drug-resistant bacteria?

Trimethoprim is a safe, effective, and inexpensive treatment for cystitis. However, at least 25% of bacteria isolated from urine samples in general practice are now resistant to trimethoprim in the laboratory. The relationship between laboratory resistance and clinical outcome is complex. Cephalexin appears to be more active than trimethoprim in the laboratory but has been consistently less effective in clinical trials. There is little point in collecting data about the prevalence of drug resistance in urinary bacteria unless it is linked to evidence about the impact of resistance on clinical outcomes. Pragmatic clinical trials are required to provide practices with clear thresholds for managing their antibiotic policies; for example, 'Change from trimethoprim to drug X when the probability of trimethoprim resistance reaches Y%.' Prescribers should be aware that trimethoprim resistance is most likely to occur in patients who have been exposed to trimethoprim or other antibiotics in the previous six months, and that the risk increases with age. This information could be used to stratify women according to risk of infection by trimethoprim-resistant bacteria. Health education leaflets are an effective method for reducing the frequency of recurrent cystitis. Symptomatic treatment can control symptoms and allow time for microbiological investigation. Both of these strategies may help to reduce unnecessary prescribing of antibiotics in general and quinolones in particular.

Economic assessment of three antimicrobial therapies for uncomplicated urinary tract infection in women.

This retrospective cohort study used North Carolina Medicaid paid-claims data to assess clinical and economic outcomes of treatments for urinary tract infection (UTI). The study population comprised female Medicaid recipients, between 15 and 64 years of age, with a paid claim filed for a primary diagnosis of UTI or acute UTI from January 1 to June 30, 1994, who were treated with ciprofloxacin, nitrofurantoin, or trimethoprim/sulfamethoxazole (TMP/SMZ). Patients had follow-up for 6 months after the primary diagnosis. Patients who did not receive further treatment for UTI with 1 of the 3 drugs within 30 days after initial treatment were assumed to be cured. Costs were measured as the sum of reimbursements for UTI-related medical services and drug treatments. Outcomes for 409 patients were assessed. Cure rates of initial treatment with ciprofloxacin, nitrofurantoin, and TMP/SMZ were 81%, 88%, and 93%, respectively. Cost-effectiveness ratios of initial treatment with the 3 drugs were $150.80, $81.20, and $69.00, respectively. When efficacy rates generated from published randomized clinical studies were applied, cost-effectiveness ratios for the 3 drugs were $130.96, $86.17, and $72.00, respectively. A decision model of treatment pattern and associated costs is presented. Several patient variables indicate that the ciprofloxacin group included more severe cases of UTI than did the other groups. Study limitations, confounders, and future research suggestions are discussed. Our results show that treatment for >7 days results in a better cure rate regardless of the drug used than does treatment for < or =7 days and that TMP/SMZ is the most cost-effective of the 3 drugs for UTI or acute UTI.

A survey of horses with acute diarrhoea: diagnosis, assessment of the prognosis, and comparison of two antibiotic therapies.

Twenty horses, ponies, and foals referred with acute diarrhoea were divided at random into two treatment groups. One group was treated intravenously with trimethoprim/ sulfadiazine and the other group with ampicillin/gentamicin. Both groups were given the same standardized symptomatic therapy. All animals were evaluated clinically and 5 variables (general impression, heart rate, rectal temperature, appetite, and consistency of the faeces) were estimated on a five point scale (0-4). Jugular blood samples were taken at admittance and at regular intervals for routine screening. Three blood variables (packed cell volume, white blood cell count, and base excess) were also classified in a 5-point scale. The 'diarrhoea prognosis index' was the total sum of the eight variables scaled. Faecal samples were cultured aerobically and examined for worm eggs and larvae. A definite diagnosis was only reached in 11 horses (55%). Salmonellosis and parasitic infections were the most common causes of the diarrhoea. Seven horses (35%), three from the ampicillin/gentamicin group and four from the trimethoprim/sulfadiazine group, died or were euthanized because of a poor prognosis. Only the packed cell volume differed significantly between horses that died and horses that survived. No single clinical or haematological/biochemical variable did forecast the prognosis for the individual patient reliably, nor did the 'diarrhoea prognosis index'. The only reliable indication for the outcome of an individual horse appeared to be the clinical response to treatment within 4 days. The clinical outcome of both treatment groups did not differ significantly. In conclusion, it was difficult to reach a specific diagnosis in these horses with diarrhoea. It was not possible to forecast the prognosis of an individual patient by a single variable or by a combination of variables. No significant differences were found between the two antibiotic treatment groups.

Comparison in prescribing patterns of antibacterial drugs in salmonid farming in Norway during the periods 1980-1988 and 1989-1994.

The choice of antibacterial drugs for the treatment of bacterial diseases in farmed salmonids changed dramatically during the period 1980-1994. In terms of treatment doses, oxytetracycline chloride was the most frequently prescribed antibacterial drug during the periods 1980-1983 and 1985-1986. In 1984, prescriptions changed in favour of furazolidone and trimethoprim/ sulphadiazine (1:5). Oxolinic acid was introduced for use in farmed fish in Norway in 1987, and immediately became the drug of choice, comprising 36% and 50% of the prescribed treatment doses in 1987 and 1988, respectively. In 1989, flumequine was temporarily approved for use in farmed salmonids, and during the period 1989-1994 antibacterial drug therapy in farmed salmonids acquired the character of "mono-therapy' with the quinolones flumequine and oxolinic acid. This rapid change-over in the choice of drug may partly be explained by the development of bacterial drug resistance in farmed salmonids, both to oxytetracycline and trimethoprim/sulphadiazine. The prescribing of furazolidone declined to zero during the study period. The morbidity caused by bacterial infections was defined as the number of treatment doses of antibacterial drugs per kg biomass of farmed salmonids per year. It was estimated that during the period 1988-1995, an average of 39% (mean value) of farmed salmon received, in theory, an antibacterial cure once each year. In comparison, the corresponding figure for the period 1981-1988 was 60%. However, in 1993 this figure fell to 13%, and declined even further in 1994 to 2.3%. The practice of on-farm mixing of medicated feed, using prescribed raw materials (pure drug substances) or premix formulations, declined significantly during the period 1992-1994. This was due to the introduction, in 1992, of new regulations on the prescribing of drugs to farmed fish.