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[Optimizing antibiotics policy in the Netherlands. V. SWAB guidelines for perioperative antibiotic prophylaxis. Foundation Antibiotics Policy Team].

The Stichting Werkgroep Antibioticabeleid (SWAB, Foundation Antibiotics Policy Team) has issued guidelines for perioperative antibiotic prophylaxis in Dutch hospitals. Antibiotic prophylaxis is generally recommended for surgical procedures with relatively high postoperative infection rates and those in which consequences of infection are really serious. Studies have revealed that prophylaxis given within two hours before incision is most effective. Short-term, preferably single-dose prophylaxis, is as effective as multiple-dose prophylaxis in most procedures. For reasons of cost effectiveness and prevention of induction of resistance, single-dose prophylaxis is recommended. The antimicrobial agent of choice for perioperative prophylaxis should not be widely used as a therapeutic agent, should be selectively active against micro-organisms most frequently isolated from surgical site infections, and should have a plasma-half-life that makes single-dosing possible for most operations. Therefore cefazoline is an agent that is widely used for perioperative prophylaxis.

Antibiotic Prophylaxis↗

Isolation of a new antibiotic 333-25, related to antibiotic EM 49. (Studies on antibiotics from the genus Bacillus. XI).

A new antibiotic, 333-25, active against Gram-positive and Gram-negative bacteria, was isolated from the culture broth of Bacillus circulans 333-25. The antibiotic is a basic acylpeptide containing 2,4-diaminobutyric acid (5), leucine (2), phenylalanine (1) and a fatty acid. It is closely related to antibiotic EM 49, but can be differentiated by chromatographic behaviour.

Animals↗

Neo-enactin, a new antifungal antibiotic potentiating polyene antifungal antibiotics. II. Taxonomic studies of the producing microorganism and simultaneous production of bleomycin group and streptothricin-like antibiotics.

A new antifungal antibiotic, named neo-enactin, was produced mainly in the mycelia of strain H 829-MY 10. Strain H 829-MY 10 was identified as a Streptoverticillium, determined to be nonchromogenic, and fits in the white color-series. Although Streptoverticillium olivoreticuli is known to be chromogenic, strain H 829-MY 10 is most related to that species. Thus, strain H 829-MY 10 is named as Streptoverticillium olivoreticuli subsp. neoenacticus. Besides neo-enactin, two bleomycin-group antibiotics and two streptothricin-like antibiotics were simultaneously produced by strain H 829-MY 10.

Anti-Bacterial Agents↗

Antibiotics for acute maxillary sinusitis.

OBJECTIVES: For adults seeking care in ambulatory practices, sinusitis is the most common diagnosis treated with antibiotics. We examined whether antibiotics are indicated for acute sinusitis, and if so, which antibiotic classes are most effective. SEARCH STRATEGY: Relevant studies were identified from searches of MEDLINE and EMBASE in October 1998, contacts with pharmaceutical companies and bibliographies of included studies. SELECTION CRITERIA: Randomized trials were eligible that compared antibiotic to control or antibiotics from different classes for acute maxillary sinusitis. Additional criteria were diagnostic confirmation by radiograph or sinus aspiration, outcomes that included clinical cure or improvement and a sample size of 30 or more adults. Of 1784 potentially relevant studies, two or more reviewers identified 32 studies meeting selection criteria. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by 2 persons and synthesized descriptively. Some data were analyzed quantitatively using a random effects model. Primary outcomes were a) clinical cure and b) clinical cure or improvement. Secondary outcomes were radiographic improvement, relapse rates, and dropouts due to adverse effects. MAIN RESULTS: Thirty-two trials, involving 7,330 subjects evaluated antibiotic treatment for acute maxillary sinusitis. Major comparisons were antibiotic vs. control (n=5); newer, non-penicillin antibiotic vs. penicillin class (n=10); and amoxicillin-clavulanate vs. other extended spectrum antibiotics (n=10). Most trials were conducted in otolaryngology settings. Only 5 trials described adequate allocation and concealment procedures; 10 were double-blind. Compared to control, penicillin improved clinical cures [relative risk (RR) 1.72, 95% CI 1.00 to 2.96]. Treatment with amoxicillin did not significantly improve cure rates (RR 2.06; 95% CI 0.65 to 6.53), but there was significant variability between studies. Radiographic outcomes were improved by antibiotic treatment. Comparisons between classes of antibiotics showed no significant differences: newer non-penicillins vs. penicillins (RR for cure 1.07; 95% CI 0.99 to 1.17); newer non-penicillins vs. amoxicillin-clavulanate (RR for cure 1.01, 95% CI 0.97 to 1.04). Compared to amoxicillin-clavulanate, dropouts due to adverse effects were significantly lower for cephalosporin antibiotics. Relapse rates within one month of successful therapy were 5%. REVIEWER'S CONCLUSIONS: For acute maxillary sinusitis confirmed radiographically or by aspiration, current evidence is limited but supports penicillin or amoxicillin for 7 to 14 days. Clinicians should weigh the moderate benefits of antibiotic treatment against the potential for adverse effects.

Acute Disease↗

Antibiotics for the common cold.

BACKGROUND: The common cold is caused by viruses which cannot be helped by antibiotics. OBJECTIVES: The objective of this review was to assess the effects of antibiotics for the common cold. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, the Family Medicine Database, and reference lists of articles, and we contacted principal investigators. The most recent search was in December 1998. SELECTION CRITERIA: Randomised trials comparing any antibiotic therapy with placebo in acute upper respiratory tract infections. DATA COLLECTION AND ANALYSIS: Both reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Main results: Seven trials involving 2056 people aged between six months and 49 years were included. The overall quality of the included trials was variable. People receiving antibiotics did not do better in terms of cure or improvement than those on placebo (odds ratio 0.95, 95% confidence interval 0.70 to 1.28 fixed effects model). One study found a significant benefit for antibiotics compared with placebo for runny nose (clear or purulent). The only other study to evaluate purulent nasal discharge found no significant benefit for antibiotics. Only one study reported work time lost with 22% of those on antibiotic treatment and 25% of those on placebo but this was not significant. Patients treated with antibiotics had a significant increase in side effects (odds ratio 2.72, 95% confidence interval 1.02 to 7.27, random effects model). REVIEWER'S CONCLUSIONS REVIEWERS' CONCLUSIONS: There is not enough evidence of important benefits from the treatment of upper respiratory tract infections with antibiotics and there is a significant increase in adverse effects associated with antibiotic use.

Anti-Bacterial Agents↗

Nebulised anti-pseudomonal antibiotics for cystic fibrosis.

BACKGROUND: Lung damage associated with persistent infection by Pseudomonas aeruginosa is the major cause of morbidity and mortality in people with cystic fibrosis. Nebulised antibiotics are commonly used for treatment of this infection. OBJECTIVES: To examine the evidence that nebulised anti-pseudomonal antibiotic treatment in patients with cystic fibrosis reduces frequency of exacerbations of infection, improves lung function, quality of life and survival. To assess adverse effects of nebulised anti-pseudomonal antibiotic treatment. SEARCH STRATEGY: Trials were identified from the Cochrane Cystic Fibrosis and Genetic Disorders Group clinical trials register. Companies which marketed nebulised anti-pseudomonal antibiotics were contacted for information on unpublished trials. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: Trials were selected if, nebulised anti-pseudomonal antibiotics treatment was used in patients with cystic fibrosis, treatment was used for four weeks or more, allocation to treatment was randomised or pseudo-randomised, and there was a placebo or a no placebo control group. DATA COLLECTION AND ANALYSIS: References to nebulised antibiotics were retrieved from the register. Two reviewers independently selected trials from this sample according to the criteria. Each judged the quality of selected trials. One reviewer extracted data from these trials. MAIN RESULTS: Ten trials with 758 participants were included in the review. Sixty eight % of participants were in one trial. Duration of trials ranged from one to 32 months. There was large variation in study design and outcome measures which limited meta-analysis. Lung function measured as forced expired volume in one second (FEV1) was generally better in the treated groups than in control groups but a pooled estimate of effect was not possible. In the largest trial of 520 participants the FEV1 was 11.9% predicted (95% confidence interval 8.1to 15.6) higher in the treated group than in the placebo control group after 5 months. In three trials with 581 participants the number of participants having at least one hospital admission during a trial was reduced in the groups treated with nebulised antibiotics, odds ratio 0.69 (95% confidence Interval 0.50 to 0.96). In two trials with 591 participants the number of participants having and at least one course of antibiotic therapy was reduced in the treated group, odds ratio 0.62 (95% confidence interval 0.45 to 0.87). There was no evidence of renal or auditory toxicity. Resistance to antibiotic increased more in the antibiotic treated group than in placebo group. The most evidence for a single drug is for tobramycin, which was used in total daily doses from 40mg to 1800mg. REVIEWER'S CONCLUSIONS: Nebulised anti-pseudomonal antibiotic treatment improves lung function and reduces frequency of exacerbations of infection in people with cystic fibrosis. There is a need for more evidence for effect on quality of life and survival, for longer duration trials to determine if this benefit is maintained and to determine the significance of development of antibiotic resistant organisms.

Administration, Inhalation↗

Antibiotics for sore throat.

BACKGROUND: Sore throat is a very common reason for people to attend for medical care. Sore throat is a disease that remits spontaneously, that is, 'cure' is not dependant on treatment. Nonetheless primary care doctors commonly prescribe antibiotics for sore throat and other upper respiratory tract infections. OBJECTIVES: To assess the benefits of antibiotics in the management of sore throat. SEARCH STRATEGY: Systematic search of the literature from 1945 to 1999, using electronic searches of MEDLINE (using the keywords, "pharyngitis", "sore throat" and "tonsillitis") after 1966, the Cochrane Library, the Cochrane collection of hand-searched trials, and the reference sections of the articles identified. Abstracts of identified articles were used to determine which studies were trials. SELECTION CRITERIA: Trials of antibiotic against control with either measures of the typical symptoms (throat soreness, headache or fever), or complications (suppurative and non-suppurative) of sore throat. DATA COLLECTION AND ANALYSIS: RevMan 4.0.3 MAIN RESULTS: A total number of 10,484 cases of sore throat have been studied. 1. Non-suppurative complications There was a trend for protection against acute glomerulonephritis by antibiotics, but insufficient cases were recorded to be sure of this effect. Several studies found benefit from antibiotics for acute rheumatic fever, which reduced this complication to less than one third (OR = 0.30; 95% CI = 0.20-0.45). 2. Suppurative complications Antibiotics reduced the incidence of acute otitis media to about one quarter of that in the placebo group (OR = 0.22; 95% CI = 0.11-0.43) and reduced the incidence of acute sinusitis to about one half of that in the placebo group (OR = 0.46; 95% CI = 0.10-2.05). The incidence of quinsy was also reduced in relation to placebo group (OR = 0.18; 95% CI = 0.08-0.43). 3. Symptoms Symptoms of headache, throat soreness and fever were reduced by antibiotics to about one half. The greatest time for this to be evident was at about three and a half days (when the symptoms of about 50% of untreated patients had settled). About 90% of treated and untreated patients were symptom-free by one week. 4. Subgroup analyses of symptom reduction Subgroup analysis by age; blind vs unblinded; us of antipyretics; or results of swabs for Streptococcus yielded no significant differences. REVIEWER'S CONCLUSIONS: Antibiotics confer relative benefits in the treatment of sore throat. However, the absolute benefits are modest. Protecting sore throat sufferers against suppurative and non-suppurative complications in modern Western society can only be achieved by treating many with antibiotics who will derive no benefit. Antibiotics shorten the duration of symptoms, but by a mean of only about half of one day at day 3 (the time of maximal effect), and by about eight hours overall.

Anti-Bacterial Agents↗

Antibiotics for preterm labour with intact membranes.

BACKGROUND: There may be a link between infection and preterm birth. OBJECTIVES: Since rupture of the membranes is an important factor in the progression of preterm labour, it is important to see if antibiotics are of any benefit prior to membrane rupture. The objective of this review was to assess the effects of antibiotics administered to women in preterm labour with intact membranes, on maternal and neonatal outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and reference lists of articles. We contacted experts in the field. SELECTION CRITERIA: Randomised trials which compared antibiotic treatment with placebo or no treatment for women in preterm labour (between 20 and 36 weeks gestation) with intact membranes. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for missing data. MAIN RESULTS: Meta-analysis of the ten included trials demonstrated a statistically significant prolongation of pregnancy associated with the use of antibiotics (5. 4 days, 95% confidence interval (CI) 0.9- 9.8 days). Antibiotic treatment was also associated with a statistically significant reduction in maternal infection (odds ratio (OR) 0.59, 95% CI 0.36, 0.97) and neonatal necrotising enterocolitis (OR 0.33, 95% CI 0.13, 0.88). No statistically significant effect was detected on the neonatal outcomes of respiratory distress syndrome and neonatal sepsis, although there was a trend towards the latter (OR 0.67, 95% CI 0.42, 1.07). An increase in perinatal mortality was observed in the group receiving antibiotics (OR 3.36, 95% CI 1.21, 9.32). REVIEWER'S CONCLUSIONS: Although a prolongation in time to delivery and a trend towards a reduction in neonatal sepsis was detected, this review fails to demonstrate a clear overall benefit from antibiotic treatment for preterm labour with intact membranes on neonatal outcomes and raises concerns about increased perinatal mortality for those who received antibiotics. This treatment cannot therefore be currently recommended for routine practice. Further research is required to identify a subgroup of women (and their babies) who are more likely to experience benefit from antibiotic treatment for preterm labour prior to membrane rupture, and to identify which antibiotic or combination of antibiotics is most effective. The results of the ongoing ORACLE trial should help resolve some of the uncertainties revealed by this review.

Anti-Bacterial Agents↗

Macrolide antibiotics for cystic fibrosis.

BACKGROUND: Cystic Fibrosis is characterised by chest infection, the antibiotic treatment of which has significantly improved the outlook for people with this condition. The unusual nature of organisms that infect the chest of individuals with cystic fibrosis has restricted antibiotic choice. In particular the bacteria, Pseudomonas aeruginosa, is resistant to nearly all antibiotics that can be taken by mouth. There is laboratory evidence and evidence from other disease processes that macrolide antibiotics, whilst not directly active against Pseudomonas aeruginosa, may have indirect actions against this bacteria. OBJECTIVES: This review aimed to test the hypotheses that macrolide antibiotics; 1) Improve clinical status compared to placebo or another antibiotic 2) do not have unacceptable adverse effects If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. In addition, Principal Investigators, known to work in the field and previous authors were contacted for unpublished or follow up data. Pharmaceutical companies, that manufacture macrolide antibiotics, were approached. SELECTION CRITERIA: Randomised controlled trials, published or unpublished, of macrolide compared to placebo, another class of antibiotic or another macrolide. Studies which compare regimes of the same macrolide at different doses will also be included. DATA COLLECTION AND ANALYSIS: No completed randomised controlled trials were identified. MAIN RESULTS: Three open studies excluded. Four ongoing randomised controlled trials were identified. No completed randomised controlled trials were identified. REVIEWER'S CONCLUSIONS: At present, there are no randomised controlled trials to evaluate the use of macrolide antibiotics for the treatment of chest infection in people with cystic fibrosis. Such trials, with clear outcome measures, are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Anti-Bacterial Agents↗

Antibiotics for acute bronchitis.

BACKGROUND: Antibiotic treatment of acute bronchitis, which is one of the most common illnesses seen in primary care, is controversial. Most clinicians prescribe antibiotics in spite of expert recommendations against this practice. OBJECTIVES: People with acute bronchitis may show little evidence of bacterial infection. If effective, antibiotics could shorten the course of the disease. However if they are not effective, the risk of antibiotic resistance may be increased. The objective of this review was to assess the effects of antibiotic treatment for patients with a clinical diagnosis of acute bronchitis. SEARCH STRATEGY: We searched Medline, Embase, reference lists of articles and the authors' personal collections up to 1996, and Scisearch from 1989 to 1996. SELECTION CRITERIA: Randomised trials comparing any antibiotic therapy with placebo in acute bronchitis. DATA COLLECTION AND ANALYSIS: At least two reviewers extracted data and assessed trial quality. MAIN RESULTS: Eight trials involving 750 patients aged eight to over 65 and including smokers and non-smokers were included. The quality of the trials was variable. A variety of outcome measures were assessed. In many cases, only outcomes that showed a statistically significant difference between groups were reported. Overall, patients receiving antibiotics had slightly better outcomes than did those receiving placebo. They were less likely to report feeling unwell at a follow up visit (odds ratio 0.42, 95% confidence interval 0.22 to 0.82), to show no improvement on physician assessment (odds ratio 0.43; 0.23 to 0.79), or to have abnormal lung findings (odds ratio 0.33, 95% confidence interval 0.13 to 0.86), and had a more rapid return to work or usual activities (weighted mean difference 0.7 days earlier, 95% confidence interval 0.2 to 1. 3). Antibiotic-treated patients reported significantly more adverse effects (odds ratio 1.64; 1.05 to 2.57) such as nausea, vomiting, headache, skin rash or vaginitis. REVIEWER'S CONCLUSIONS: Antibiotics appear to have a modest beneficial effect in the treatment of acute bronchitis, with a corresponding small risk of adverse effects. The benefits of antibiotics may be overestimated in this analysis because of the tendency of published reports to include complete data on only the outcomes found to be statistically significant.

Acute Disease↗

Antibiotic prophylaxis for surgery for proximal femoral and other closed long bone fractures.

BACKGROUND: Antibiotic prophylaxis has been established policy for major surgical operations for many years. In fracture fixation, the effectiveness, and the duration of administration, have been a matter of debate. OBJECTIVES: To assess the effects of the prophylactic administration of antibiotics in patients undergoing surgical management of hip or other long bone fractures. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Current Contents, Dissertation Abstracts, and Index to UK Theses, and bibliographies of identified articles. Trials were also obtained from the Cochrane Musculoskeletal Injuries Group trials register. Date of the most recent search: end of 1997. SELECTION CRITERIA PARTICIPANTS: Any patients with a hip or other closed long bone fracture undergoing surgery for internal fixation or replacement arthroplasty. INTERVENTIONS: Any regimen of systemic antibiotic prophylaxis administered at the time of surgery. OUTCOME MEASURES: Wound infection (deep and superficial), urinary tract infection, respiratory tract infection, adverse effects of prophylaxis, economic evaluations. DATA COLLECTION AND ANALYSIS: Both reviewers independently selected trials for inclusion, and assessed methodological quality and extracted data. Where possible, data were pooled and Peto odds ratios and absolute risk reductions, each with 95% confidence intervals, calculated. MAIN RESULTS: Twenty one randomised trials of only poor or moderate quality were included. The comparisons tested fell within six comparison groups, principally multiple dose or a single dose of antibiotic versus a placebo or no treatment. Antibiotic prophylaxis reduces wound, urinary and respiratory tract infections in patients undergoing surgery for closed fracture fixation. Economic modelling has indicated that this is a cost-effective intervention. There are limited data for the incidence of adverse effects, but as expected they appear to be more common in those receiving antibiotics. REVIEWER'S CONCLUSIONS: Antibiotic prophylaxis should be offered to those undergoing surgery for closed fracture fixation. On ethical grounds, further placebo controlled randomised trials of the effectiveness of antibiotic prophylaxis in closed fracture surgery are unlikely to be justified. Trials addressing the cost-effectiveness of different effective antibiotic regimens would need to be very large and may not be feasible.

Antibiotic Prophylaxis↗

Antibiotic medication and bacterial resistance to antibiotics: a survey of children in a Vietnamese community.

OBJECTIVE: To investigate antibiotic use and antibiotic susceptibility of respiratory tract pathogens in children aged 1-5 years in Bavi, Vietnam. METHOD: Nasopharynx and throat specimens were collected from 200 children from randomly selected households in a demographically defined population. Respiratory isolates were tested for antibiotic susceptibility according to the standard disk diffusion method. A questionnaire survey of carers elicited information on type of antibiotic used, duration of treatment, where the antibiotics had been purchased, type of treatment information retained by carers and episodes of illness preceding the study. RESULTS: 82% of the children had at least one symptom of acute respiratory tract infection (ARI) in the 4 weeks prior to the study, and of these 91% were treated with antibiotics. The most commonly used antibiotics were ampicillin (74%), penicillin (12%), amoxicillin (11%), erythromycin (5%), tetracycline (4%) and streptomycin (2%). Ampicillin was used for 3.3 days on average (SD:1.8) and penicillin for 2.6 days (SD:0.7). When deciding which antibiotic to use, 67% of the carers consulted the pharmacy seller, 11% decided themselves and 22% followed the doctor's prescription. The carrier rate of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis was 50%, 39% and 17%, respectively. Isolates from 145 children were susceptibility tested, and 74% were found to carry resistant pathogens. Of the tested isolates, 90% of S. pneumoniae, 68% of H. influenzae and 74% of M. catarrhalis were resistant to at least one antibiotic. The mean number of antibiotics (susceptible strains excluded) to which resistance was found was 2.0 (SD:1.2), 2.5 (SD:1.8) and 2.1 (SD:0.9), respectively. S. pneumoniae and H. influenzae showed high resistance to tetracycline (88% and 32%, respectively), trimethoprim/sulphonamide (32% and 44%), and chloramphenicol (25% and 24%). 23% of S. pneumoniae were erythromycin-resistant and 18% of H. influenzae isolates were resistant to ampicillin. There was a significant difference in ampicillin and penicillin resistance between the group of children previously treated with beta lactam antibiotics and the group of children who did not receive antibiotics. CONCLUSION: As reported by the carers, children in Bavi are treated with antibiotics frequently. Most antibiotics were obtained without consulting a doctor. High levels of antibiotic resistance and high prevalence of multidrug-resistant strains were found among respiratory pathogens. The existence of a large reservoir of resistance genes among children in low-income countries represents a threat to the success of antibiotic therapy throughout the world. Multi-faceted programmes to improve rational use of antibiotics in Vietnam are urgently needed.

Adult↗

Desire for antibiotics and antibiotic prescribing for adults with upper respiratory tract infections.

OBJECTIVE: Prior studies have shown that 60% to 75% of adults with upper respiratory tract infections want antibiotics. More recent research indicates declines in antibiotic prescribing for upper respiratory tract infections. To investigate whether there has been a comparable decrease in patients' desire for antibiotics, we measured the proportion of adults with upper respiratory tract infections who wanted antibiotics in the winter of 2001-2002. We also sought to identify factors independently associated with wanting antibiotics and antibiotic prescribing. DESIGN: Prospective survey of adults with upper respiratory tract infections prior to visiting an acute care clinic from November 2001 to February 2002. MEASUREMENTS AND MAIN RESULTS: Thirty-nine percent of 310 patients wanted antibiotics. Many patients wanted relief from symptoms (43%) or pain (24%) and many patients expected to receive a diagnosis (49%) or reassurance during the visit (13%). In multivariable modeling, independent predictors of wanting antibiotics were prior antibiotic use (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 to 4.7) and current smoking (OR, 3.1; 95% CI, 1.3 to 7.3). Physicians prescribed antibiotics to 46% of patients who wanted antibiotics and 29% of patients who did not want antibiotics (P=.01). In multivariable modeling, wanting antibiotics was an independent predictor of antibiotic prescribing (OR, 2.1; 95% CI, 1.1 to 4.4). CONCLUSIONS: Only 39% of adults seeking care for upper respiratory tract infections wanted antibiotics, less than in previous studies. In continuing efforts to break the cycle of inappropriate antibiotic use, physicians should not assume that most patients with upper respiratory tract infections want antibiotics.

Acute Disease↗

Trends in antibiotic use and cost and influence of case-mix and infection rate on antibiotic-prescribing in a long-term care facility.

BACKGROUND: Antibiotic use and cost indicators have been developed specifically for the long-term care facility (LTCF) setting. Approximately 50% of the variation in these indicators was explained by the variation in infection rate. The objectives of this study were to further assess the utility of the antibiotic use and cost indicators in a different LTCF and to determine the correlation of case-mix and these indicators. METHODS: Antibiotic use and cost indicators were collected monthly by unit (N = 10) and by physician (N = 6) at a 433-bed LTCF in Syracuse, New York, from February 1999 to September 2001. Indicators included incidence (number of antibiotic courses per 1000 resident care-days) of antibiotic use, antibiotic utilization ratio ([AUR]; ratio of the number of antibiotic-days to the number of resident care-days), cost per antibiotic-day, and cost per resident care-day. Case-mix variation was measured with the case-mix index (CMI) of the Resource Utilization Group II system. Simple linear and multilinear regression analyses were used to evaluate correlations of continuous variables. RESULTS: Among the 10 units or 6 physicians, there was a significant difference in the average values for all indicators. Correlation between unit- or physician-specific CMI and antibiotic use or cost indicators or infection rate was poor. However, there was a significant positive correlation between unit- or physician-specific infection rate and incidence of antibiotic use, AUR, and cost per resident care-day but not cost per antibiotic-day. With use of multilinear regression analysis to control for CMI and cost per antibiotic-day, infection rate was a significant predictor of incidence of antibiotic use (R2 = 0.65; P <.001) and AUR (R2 = 0.78; P <.001). CONCLUSIONS: This study provides further evidence that the antibiotic use and cost indicators developed specifically for LTCFs can detect significant variation among units within a facility and among physicians. However, there was no correlation between CMI and antibiotic use or cost indicators. After controlling for case-mix variation and cost per antibiotic-day, variation in infection rate explained most of the variation in incidence of antibiotic use and AUR.

Anti-Bacterial Agents↗

Nature of gram-negative rod antibiotic resistance during antibiotic rotation.

PURPOSE: The aim of this study was to characterize the evolution of gram-negative antibiotic resistance during a study of empiric antibiotic rotation. METHODS: We showed previously that quarterly rotation of a single antibiotic class is inferior to cycling two antibiotics per quarter for empiric treatment of gram-negative rod (GNR) infections, as evidenced by increased incidence of antibiotic-resistant GNR (rGNR) infections. Resistance patterns were examined by quantifying GNRs resistant to one or more of the following drug classes: Aminoglycosides, cephalosporins, carbapenems, fluoroquinolones, or piperacillin-tazobactam. For all rGNR isolates, the mean number of antibiotic classes to which an organism was resistant was calculated per quarter, as was the number of rGNR species. RESULTS: Single-antibiotic rotation (SAR) was associated with significant increases in the incidence of piperacillin-tazobactam (p < 0.0005) and cephalosporin (p = 0.003) resistance, reaching nearly 25% and 30% of rGNR isolates respectively, most notably during the quarter of designated cephalosporin use (VI). Multi-drug resistance emerged over time; resistant classes/resistant GNR isolates ranged from 1.2 in the dual-antibiotic rotation (DAR) to 1.9 in the SAR period (p = 0.02). Resistance was evident in an increasing number of unique GNR species. On average, 1.3 species were isolated per month in the DAR period and 3.0/month in the SAR period (p = 0.004), but proportionally, no single GNR species became significantly more resistant across time. Compared to only 5.8% in the DAR period, 29% noncompliance was observed in the SAR, with a six-fold increase in the use of nonscheduled empiric antibiotics due to the presence of an organism resistant to the scheduled rotation drug. CONCLUSIONS: A single-antibiotic rotation is associated with increased incidence and heterogeneity of resistant GNR isolates, as well as increased multiple-drug-class resistance. The attenuation of resistance observed in the single-antibiotic rotation may reflect the effect of unintended antibiotic heterogeneity driven by increasing resistance to the antibiotic class recommended for use each quarter. This suggests that reliance on a single antibiotic class for empiric treatment of GNR infection exerts sufficient pressure within the environment to encourage the development of diversified resistance, as well as cross-resistance over antibiotic classes, thus narrowing the availability of effective antibiotic treatment.

Anti-Bacterial Agents↗

[Surveillance of antibiotic resistance and antibiotic consumption in Medimurje].

INTRODUCTION: Bacterial resistance is a global problem. More than 60 years of the large-scale use of antibiotics have resulted in a number of microorganisms which are resistant or multiresistant to different antimicrobial drugs. A correlation between the use of antibiotics and bacterial resistance has been proved for many different groups of antibiotics. AIM: The aim of this study was to determine the connection between bacterial resistance and antibiotic consumption in the region. MATERIAL AND METHODS: The surveillance of antibacterial resistance in Medimurje started in 1997 as part of the activities of the Croatian Commitee for Antibiotic Resistance Surveillance at the Academy of Medical Sciences of Croatia. The utilization of antibiotics was defined according to WHO and expressed in defined daily doses. The surveillance of their consumption and comparison of different drugs and different regions is done by TID (Thousands of Inhabitants Daily), which describes the population proportion taking a drug in a particular region per day. The analysis of antibiotic consumption was based on distribution data. RESULTS: The consumption of antibiotics according to the ATC/TID system in Medimurje in 2002 was 18.06 TID; TID was 0.86 and 17.2 for inpatients and outpatients, respectively. The consumption was recorded for the penicillin group of antibiotics in both hospital and outpatient utilization, followed by cephalosporins, tetracyclines and macrolides in outpatient utilization, and by cephalosporins, aminoglycosides and quinolones in hospital utilization. Analysis of the consumption of the penicillin group of antibiotics in outpatient utilization revealed it to be predominated by the wide spectrum penicillins and co-amoxiclav, whereas the latter prevailed in hospital utilization. The surveillance of bacterial resistance in Medimurje during the last 5 years (1998-2002) pointed to a high resistance to macrolides (23%-33%) in BHS. The outpatient utilization of macrolides was on the 4th place with 1.15 TID. Azithromycin accounted for 87% of macrolide consumption. In this region, pneumococci showed an extremely high rate of penicillin resistance (49%-68%), although this resistance was mostly intermediate. It was obviously due to the high selective antibiotic requirements, especially for the strains involving respiratory tract. High resistance to macrolides (15%-38%), cotrimoxasol (42%-50%) and tetracyclines (30%) pointed to the high proportion of multiresistant pneumococcal strains. A significantly lower resistance to penicillin (30%), which was strictly intermediate, was recorded in isolates from primary sterile materials. Resistance to other antibiotic groups was also lower. The rate or MRSA in the group of S. aureus as 2%-3% in the five-year period. E. coli was the most frequent isolate in both inpatient and outpatient settings. Analysis of resistance during the last 5 years yielded no specific findings. The resistance of wide spectrum penicillin was 51%-58%, with a very low portion of ESBL strains (<1%), no imipenem resistant strain; resistance to quinolones was 4%-8%, and to cotrimoxasole was 30%. There were no invasive E. coli strains resistant to 2nd and 3rd generations of cephalosporins, aminoglycosides, quinolones and carbapenemes, while the resistance to wide spectrum penicillin, 1st generation cephalosporins and cotrimoxasole was the same as in other groups of E. coli. DISCUSSION: Surveillance of antibiotic resistance in a local region is very important, because it shows the local pattern of resistance, helps choose useful empirical therapy and most efficacious antibiotic therapy, and can modify antibiotic therapy accordingly. CONCLUSION: There is no clear correlation between antibiotic consumption and bacterial resistance, especially in case of outpatient isolates.

Anti-Bacterial Agents↗

Antigenicity of beta-lactam antibiotic preparations: production of IgE antibodies to beta-lactam antibiotic and their cross-reaction within the antibiotic group.

BALB/C mice were immunized with conjugate of benzylpenicillin or ampicillin with Ascaris suum extract. The mice developed IgE antibodies to penicillin, which were found to react with commercially available penicillin preparations in the PCA system. Elimination of polymerized penicillin by Sephadex chromatography from tested preparations could not diminish their activities to elicit PCA. High pressure liquid chromatographic (HPLC) separation of PcG preparation yielded fractions unable to elicit PCA. On the other hand, all fractions from ABPC retained the activity even after the HPLC purification. A comparative estimation of cross-reactivity of IgE and IgE antipenicillin antibodies showed that IgE antibodies cross-reacted with a variety of beta-lactam antibiotics in a high degree.

Ampicillin↗

Relationship between the number of different antibiotics used and the total use of antibiotics in European hospitals.

OBJECTIVES: The aim of this study was to establish whether there was a relationship between the number of antibacterial agents used and total antibiotic use in European hospitals. METHODS: A total of 139 hospitals from 30 countries supplied data on antibiotic use (ATC group J01) for 2001, expressed as the number of defined daily doses per 100 occupied bed-days (DDD/100 BD) and also numbers of different antibiotics used. RESULTS: Participating hospitals used a median of 46 antibiotics in 2001 (range 16-82). The most frequently used antibiotic per hospital accounted for a median of 16.5% (range 7.2-60.9%) of total use and the 10 most frequently used agents accounted for a median of 73.7% (range 53.0-98.5%) of total use. Numbers of antibiotics used varied significantly by European geographical region (Kruskal-Wallis test, P = 0.001). The median total antibiotic use was 49.6 DDD/100 BD. A statistically significant relationship was found between the number of antibiotics used and total antibiotic use (Spearman's rank, r = 0.40 and P < 0.01) for all hospitals. Individual correlations were significant in Western (r = 0.57, P < 0.01) and Southern Europe (r = 0.67, P < 0.01) only. CONCLUSIONS: The quantitative use of antibiotics in European hospitals was highly variable as was the number of different antibiotics used. In the two areas exhibiting highest total use, the greater the number of antibiotics used, the higher the total use of these drugs. Intervention studies are now needed to ascertain whether or not successful antibiotic restriction policies can reduce total antibiotic use and subsequently reduce antibiotic resistance.

Anti-Bacterial Agents↗