Search

Traditional β-lactam antibiotic dosing does not consider physiological changes in medical conditions such as sepsis. Optimal antibiotic exposure could be achieved by therapeutic drug monitoring (TDM). This review gives a brief summary. Current studies are sparse, but suggestive of a potential beneficial role of TDM to patients with reduced renal function, obese patients and the critically ill. TDM can potentially reduce adverse effects and optimise antibiotic exposure. However, standardised TDM methods are lacking and randomised clinical studies are warranted in order to prove clinical benefit.

Urinary tract infection is common in the elderly, and the prevalence increases with age due to pathological changes in the urinary tract and common use of bladder catheter. The increasing incidence of asymptomatic bacteriuria, together with fewer classical dysuria symptoms complicates the diagnosis in the elderly. There is also an increasing prevalence of complicated urinary tract infection including septicaemia. Due to an increase in antibiotic resistance urine culture should precede the choice of antibiotic treatment. Treatment duration is seven days; 14 days in patients with pyelonephritis. Adverse effects are notably higher in the elderly.

Antibiotic treatment of elderly patients implies special problems because of higher probability of reduced renal or other organ function, and interactions with other medications. Elderly patients are more often previously hospitalised and treated with antibiotics or live in health-care institutions, and may be colonised with resistant microorganisms. It is crucial to sample for microbiological diagnostics before therapy. Adverse effects of antibiotics are seen more frequently with increasing age. Otherwise, the effect of antibiotics and durations of therapy is independent of patient age.

The growth promoter story in the 1990 s increased the focus on antibiotic misuse and related resistance. A Danish EU conference, The Microbial Threat, in 1998 resulted in The Copenhagen Recommendations, on the basic principles for a policy to contain resistance, which was transformed into EU recommendations in 2001. Following this a range of programs on monitoring of resistance and consumption, research, national campaigns etc. has been accomplished. The US, Canada and Australia have also upgraded their efforts in this area, while the WHO lacks resources to approach the countries in the rest of the world, in which these problems are the worst.

Use of an antibiotic may not only select for resistance against the agent itself, but may at the same time co-select for resistance against other antibiotics if resistance genes are linked on e.g. a plasmid. Resistance plasmids may also carry genes mediating resistance against metals and disinfectants. Therefore, abundant use of metals, e.g. copper and zinc for growth promotion in animals used for food, may also co-select for antibiotic resistance. The same applies to disinfectants, e.g. silver and chlorhexidine. Prudent use of antibiotics and these other agents is essential to control antibiotic resistance.

The importance of the animal reservoir for emergence of antimicrobial resistance in bacteria in humans is difficult to estimate. In this article we give our estimate of the importance and also highlight on which points we have become wiser during recent years. We conclude that it still is the human usage of antibiotics which contributes most to resistance observed in humans, but also that the contribution from animals is large and larger than estimated just a few years ago. This indicates the need to implement restriction on antimicrobial usage for both humans and animals.

Although old techniques remain important, new techniques offer new possibilities. Mutations conferring resistance to rifampin and isoniazid can be detected in primary specimens from infectious pulmonary cases. Infections can be detected with interferon-gamma release assays, and chains of transmission can be detected by mycobacteria interspersed repetitive units. Centralized diagnostics makes it possible to apply results of routine analyses in national and international surveillance.

Antibiotic consumption has increased by around 50% in Danish hospitals over the last 7 years. In percentages, the highest increase has been among broad spectrum antibiotics such as cephalosporins, crabapenems and fluoroquinolones. The consequence of this is selection of resistant bacteria and fungi. Control of antibiotic resistance requires implementation of different strategies: better and more rapid diagnosis of infectious origin, restriction on antibiotic use, e.g. through re-evaluation every 2-3 days of patients receiving antibiotics, optimization of dosing and duration of treatment, preferred use of narrow spectrum antibiotics and optimization of hospital hygiene.

Introduction: The aim of the study was to investigate the use of antibiotics in scheduled and acute colorectal surgery in Denmark and on the basis of this and a literature research, to recommend possible antibiotic strategies., Material and Methods: In 2004, a written questionnaire regarding the antibiotic treatment in scheduled operations for colorectal cancer and acute colorectal surgery was submitted to all 39 surgical departments in Denmark which at the time performed colorectal surgical procedures., Results: The response rate was 97%. 17 different antibiotic regimes using five different kinds of drugs were used for antibiotic prophylaxis (AP) in scheduled surgery, and if antibiotic treatment was continued, 20 regimes with six different kinds of drugs were used. In case of faecal contaminations, 76% would continue the antibiotic treatment in planned surgery and 100% in acute surgery. Of these, 17% and 14% respectively were without sufficient aerobe gram-negative coverage after the operation because the treatment with ampicillin or cefuroxime was not continued on the day of the operation. For severe obese patients, 8% of the departments used higher dosage., Conclusion: None of the numerous applied antibiotic strategies were inappropriate from a microbiological point of view. However, the combination of metronidazole and ampicillin must be regarded as suboptimal due to a high prevalence of ampicillin resistant Escherichia coli. If the antibiotic treatment is continued after the operation, ampicillin or cefuroxime must be administered again later on the day of the operation. Severe obese patients need higher dosage of antibiotics. The following strategies can be recommended: Cefuroxime plus metronidazol or ampicillin plus gentamicin plus metronidazole.

Antibiotic resistance is an increasing problem world wide, although in some areas the increase in resistance is slow, as in the Nordic countries. Multiresistant staphylococci, Enterobaceriaceae and Mycobacterium tuberculosis are already causing increased morbidity, mortality and huge costs in health budgets. New effective antibiotics will not be available for the next 10-15 years, since the pharmaceutical industry has lost interest in antibiotics. The major determinant in this field, in order to save the activity of the known antibiotics, is the control of antibiotic use.

Introduction: The aim was to examine the validity in the paediatric hospital department of an antigen detection test (ADT) for the diagnosis of streptococcal tonsillitis., Material and Methods: A prospective multicenter study including three Danish paediatric hospital departments was performed from May 1, 1998 to April 30, 1999. In 353 children aged 0-14 years the result of the ADT, Clearview Strep A, was compared with the result obtained with cultivation in an aerobic culture and the clinical parameters: hyperaemia, swelling, coating, adenitis and a temperature > or = 38.5 degrees C. In 126 patients the results of the ADT were also compared with white blood cell count (WBC), neutrofil count (NC) and C-reactive protein (CRP)., Results: The prevalence of Group A Streptococci (GAS) from culture was 15%. Sensitivity, specificity, positive and negative predictive value of ADT were 67%, 95%, 72% and 94%, respectively. The positive predictive value of the ADT was significantly lower in patients aged 0-4 years than in patients aged > or = 5 years (p = 0.02). The prevalence of positive ADT was significantly higher in patients with heavy growth of GAS than in patients with moderate or sparse growth (p = 0.01). The prevalence of adenitis (p = 0.003) and coating (p = 0.003) was significantly raised in ADT-positive patients. In patients with growth of Group A Streptococci in cultivation in an aerobic culture the prevalence of adenitis (p = 0.006) and elevated CRP (p = 0.03) was significantly raised., Discussion: The sensitivity of 67% for the ADT is not satisfactory. However, in our opinion, this is not a sufficient argument against using ADT. It was a problem that the result of the ADT was sometimes difficult to read. Adjustment of the test procedure and the use of easy readable and high-sensitive optical immunoassay tests would probably improve the results significantly. Until the results of such studies exist, we suggest that the method of cultivation in an aerobic culture is used in the case of negative ADT, at least in patients with pronounced symptoms and/or clinical signs of streptococcal tonsilitis (adenitis and coating).

Infections caused by Staphylococcus aureus comprise relatively benign local skin infections, as well as serious generalised conditions. In Denmark, more than 85% of all S. aureus isolates are found resistant to penicillin, whereas resistance to methicillin is rare (< 1%) and therefore one of the penicillinase-stable penicillins is still the drug of choice. Dicloxacillin is usually chosen, because of its superior penicillinase stability. Infections caused by methicillin resistant strains may be treated with different combinations of macrolides, fusidic acid, aminoglycosides, fluoroquinolones, and rifampicin, but vancomycin is generally used. Newer drugs like the oxazolidinones and streptogramins are effective against methicillin-resistant strains and will be available in Denmark within a short time. Antibiotic treatment, however, is most often only a supplement to surgical intervention. This paper deals with the clinical picture and treatment of some common S. aureus infections.

The aim was to study whether an audit of treatment of infections in general practice resulted in changed prescribing habits. In 1995-1996 forty-six general practitioners (GP's) from the County of Roskilde participated in an audit regarding infectious diseases (incl. course participation and preparation of treatment guidelines). The effect evaluation was done on the basis of 1) two self-registrations of antibiotic prescriptions carried out with one year's interval, and 2) prescribing data from the National Insurance database collected over two periods, before the first and second self-registration respectively. The number of patients not receiving antibiotics increased significantly from 47.2% to 52.4% after intervention. The self-registration did not show any change in choice of antibiotics, while the registry data showed a shift from broad-spectrum to narrow-spectrum penicillin. This change was, however, also found among the GP's, who did not participate in the audit. The study demonstrated that audit can result in changes in prescribing patterns, but at the same time emphasizes the need for inclusion of external data sources and control groups in the evaluation of intervention effects.

Ciprofloxacin 500 mg orally twice daily was compared to pivampicillin 700 mg orally twice daily for 10 days in 172 men (41-85 years) with acute epididymitis. Failure of treatment occurred in 48 patients, in 15/76 (19.7%) receiving ciprofloxacin versus in 33/82 (40.2%) receiving pivampicillin (p = 0.006). Ciprofloxacin 500 mg orally twice daily is more effective than pivampicillin 700 mg orally twice daily and has fewer adverse events.

The central S. aureus surveillance in Denmark made it possible to analyze the clinical features of S. aureus endocarditis in a nation-wide population of non-drug addicts. Almost all cases of bacteraemia with S. aureus are reported to the Staphylococcus laboratory, Copenhagen. The medical records were reviewed in cases from 1982 to 1991 in which the diagnosis of endocarditis was reported or suspected. Two hundred and sixty patients fulfilled the diagnostic criteria. In 83 patients the diagnosis of endocarditis was not suspected clinically. The overall mortality rate among those patients whose disease was diagnosed clinically was 46% and significantly associated with late congestive heart failure, age and involvement of the central nervous system. A more frequent use of echocardiography as a screening method seems essential to improve the prognosis of patients with S. aureus endocarditis. Involvement of the CNS constitutes a relative indication for early valve replacement.

The purpose of the study was to evaluate the effect and side-effects of once daily (OD) administration of gentamicin. The study was a retrospective analysis of patients treated with gentamicin OD for at least two days for proven or suspected infection. Of the 101 patients included, 60 were female, and the median age was 64 years (range: 20-90 years). Median duration of treatment was six days (2-63 days). All patients received combination therapy with two (36 patients), three (64 patients) or four (one patient) antibiotics, apart from gentamicin usually ampicillin, cefuroxime and/or metronidazole. Gentamicin doses were usually 240 mg on a fixed basis, but reduced in patients with pre-treatment impairment of serum-creatinine. Bacteriological cultures were taken in 90% of the patients, of which 59% were positive, most often with Enterobacteriaceae (57%) or other Gram-negative rods (11%). Effect of antibiotic treatment was seen in 82% of the patients. Nephrotoxicity defined as a 44 umol/l increase in serum-creatinine during treatment was found in five patients (5%). Ototoxicity, i.e. clinical signs of tinnitus, dizziness and/or impaired hearing, was reported in two patients. In conclusion, gentamicin OD with 240 mg is easy to administer, appears to be sufficient with regard to effect and has a low frequency of side-effects.

The clinical manifestations and epidemiological data of 11 patients infected with Vibrio vulnificus found in Denmark during the unusually warm summer of 1994 are reported. All patients had been exposed to seawater prior to illness, but none had consumed seafood. Nine patients, including four with bacteraemia, developed skin manifestations of various degrees of severity. One patient died of septic shock despite surgery and treatment with relevant antibiotics. Four patients contracted the disease while fishing. High seawater temperature increases the risk of V. vulnificus infections even in temperate climates such as the Danish. Exposure to seawater, including handling of fresh seafood, during warm periods carries a risk of infection with V. vulnificus.

Despite of extensive use of antibiotics for respiratory tract infections pleural empyema is still seen as a complication to pneumonia (7-10 cases/100.000 inhabitants pr. year). Pleural empyema as a complication to pulmonary surgery is reported in 2-3% of the patients even with use of antibiotic prophylaxis. Pleural empyema is most often a serious disease of long duration. The diagnosis is obtained with microbiological and histological examination of the pleural fluid. Mixed infection occurs in over half of the cases, most often including anaerobic bacteria, but most human pathogens have been reported as etiological agents. Treatment includes drainage of pus and administration of relevant antibiotics, systemically and pleurally. Drainage can be performed via thoracocentesis, by tubes, or by resection of a part of the rib. The optimal treatment strategy is so far unknown, since good prospective comparative clinical studies are lacking.

Aminoglycosides are among the most active antimicrobial agents against Gram-negative infections, but they also share the potential for oto- and nephrotoxicity. Animal studies have shown that dosing aminoglycosides once daily is more efficient and less nephrotoxic than the conventional multiple daily dosing regimens. Pharmacokinetic and microbiological data support this finding. Clinical trials confirm that once-daily dosing is more efficient and less toxic than multiple daily dosing. The two most important risk factors for nephrotoxicity seem to be the duration of aminoglycoside treatment and high trough levels of aminoglycoside. Netilmicin and amikacin are the drugs most often used in clinical trials of once-daily dosing regimens. Recommendations for once-daily dosing of netilmicin are given.

The purpose of this study was to assess the accuracy of test strips for urinary nitrite and leucocytes for detection of bacteriuria in elderly patients. The material consisted of 213 urine samples from 85 women and 26 men (median age 79 years, range 60-93 years) within the first two days in hospital. The results of the test strip reactions were read in the department and in the laboratory. The strip test results and symptoms of UTI were compared with culture results. 27% of the samples showed significant bacteriuria on culture (> or = 10(5) colonies/ml urine). 21% of the 102 patients who had submitted two urine samples within the first two days had significant bacteriuria in both samples. Less than half of these patients had symptoms of UTI. The false negative rate of test strips (defined as the number of proven laboratory UTIs not demonstrated by the test strips, expressed as a percentage of the total number of proven UTIs) was 29% in the department and in the laboratory it was 13%. 15% of the test strips at the laboratory failed to detect significant E. coli infections which were predominant. In conclusion, we found that it is advisable to perform urine culture if symptoms of urinary tract infections are present.

The most important postoperative infections in general pulmonary surgery are empyema, pneumonia and wound infection. Risk factors are underlying malignant disease and the duration of the operation. The extent of pulmonary resection also appears to be of a certain significance. Five prospective randomized, double-blind, placebo-controlled investigations are available. Together, these investigations demonstrate that prophylactic antibiotic treatment, in which the first dose is administered immediately prior to operation, reduces the frequency of pneumonia (from 27% to 17%) and the frequency of wound infection (from 18% to 4%). Despite antibiotic prophylaxis, empyema occurs with frequency of 3%. Prophylactic antibiotic treatment has also reduced the duration of hospitalization and the postoperative employment of antibiotics. The relatively few comparative investigations have not indicated unanimously that any particular antibiotic was more advantageous than other. At present, we have insufficient knowledge about the pathogenesis of the above mentioned postoperative infections. Such knowledge could increase the possibility of other prophylatic measures.

For several years, in the Microbiological Department of Bispebjerg Hospital, it has been the routine practice that the clinical departments were contacted in connection with every sample sent for determination of aminoglycoside. During a period of 14 weeks a prospective investigation of the effect of this practice was carried out. During this period, the department received a total of 77 samples from 60 patients. Concerning 20 of these (26%), no arrangement with the department concerned could be demonstrated. The commonest causes were that the aminoglycoside treatment had been suspended at the time of taking the sample by the department concerned (14), that the sample had been taken too early (2) and the sample was not relevant (2). Considerable uncertainty reigned in the clinical departments about the exact time of taking the sample in relation to administration of antibiotics. Greater attention to these circumstances and possibly altered procedures concerning taking of samples would be useful changes. The annual saving for the department amounts to approximately 14,000 Danish crowns (approximately 1,000 pounds) but the most important advantage is considered to be early clinical contact and thus greater possibilities for therapeutic monitoring.

A prospective investigation was undertaken to compare quantitative culture of 739 samples of urine in a microbiological laboratory with the screening methods: phase contrast microscopy examination, test strip examinations for nitrite and leukocyte esterase (Multistix-2, Ames) and "Autotrak" (automatic quantitating of the bacterial content in fluids: BBT instruments). The three screening methods were, by and large, of equal value as regards true positive diagnostic frequency (0.48-0.55) and true negative diagnostic frequency (0.92). The methods were also equally rapid but microscopy examination was by far the cheapest (0.15 Danish crowns per test as compared with 1.75 for test strips and 3.10 for "Autotrak"). In addition, microscopic examination has the further advantage, although this of lesser value where cocci are concerned, of being capable of differentiating the morphology of the bacteria and their motility. It is noted that test strips have a false negative rate of approximately 13%.