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The incidence of invasive zygomycosis, a severe and often life-threatening infection, is increasing. The most common manifestations are pulmonary infection (following anti-cancer chemotherapy or haematopoietic stem-cell transplant) and invasive rhinocerebral infection (in patients with diabetes mellitus or iron overload). Iron metabolism plays an important role in the pathogenesis of infection in these high-risk populations. Rapid diagnosis, reversal of the underlying predisposition and timely surgical debridement are the underlying principles of therapy for this disease.

The 'Stichting Werkgroep Antibioticabeleid' (Dutch Working Party on Antibiotic Policy) has developed an electronic national antibiotic guide for the antibiotic treatment and prophylaxis of common infectious diseases in hospitals. This guide also contains information on the most important characteristics of antimicrobial drugs. Advice on antibiotic treatment is based on existing national evidence-based guidelines, where available. Where no guideline is available, the advice is based on an inventory of the antibiotic policies of the 12 Dutch centres with an infectious disease or medical microbiology training programme. The national antibiotic guide can be accessed through the SWAB website (www.swab.nl) and can also be downloaded on PDA/PocketPC, free of charge. Every hospital antibiotic formulary committee in the Netherlands will be offered the opportunity to edit The national version for local use.

The Dutch Working Party on Antibiotic Policy (SWAB) has revised the 1998 guideline for community-acquired pneumonia (CAP) in light of changing resistance patterns for common pathogens and new developments in epidemiology, diagnostic testing and treatment strategies. The current guideline is applicable to both primary and inpatient care, and has been developed by delegates of all professional organisations involved in the treatment of CAP, following recommendations for evidence-based guideline development. Assessment of a patient's 'severity of illness' at presentation is considered important when choosing an optimal empirical antibiotic regimen for CAP. Severely-ill patients should be treated with antibiotics covering the most important expected pathogens, including Legionella. Assessment of the severity of illness may be facilitated by the use of validated scoring systems like the pneumonia severity index and the 'confusion, urea, respiratory-rate, blood-pressure, 65-years-of-age' (CURB-65) score. Patients can also be stratified based on their location during treatment: in the community, a normal ward or an intensive-care unit. Legionella urine antigen testing is considered an important tool in the process of deciding on an optimal antibiotic regimen for CAP. Empirical therapy should be replaced with pathogen-directed therapy if the causative agent is identified.

Invasive aspergillosis remains an important cause of morbidity and mortality in patients with prolonged and severe immune suppression such as following haematopoietic stem-cell transplantation. Consensus definitions, which allow categorisation of patients based on diagnostic criteria, are an important improvement in uniform registration of invasive mycoses in clinical trials. Prospective monitoring of high-risk patients for the circulating aspergillus cell-wall component galactomannan, results in earlier diagnosis in two-thirds of patients when compared with conventional diagnostic methods. High-resolution CT (HRCT) enables the lesions characteristic of invasive mycoses to be detected earlier and better than by chest radiograph. In addition, invasive mycoses cause characteristic lesions on the HRCT scan including the halo-sign and the air-crescent sign. The pre-emptive management strategy which combines monitoring of patients for surrogate markers with a HRCT scan appears to be a promising approach to the early identification and treatment of patients with invasive aspergillosis.

For 45 years, amphotericin B has been the drug of choice for the treatment of invasive mycoses. Because of its severe toxicity, lipid-associated formulations of amphotericin B have been developed. Although comparative trials are scarce, there appears to be no convincing advantage of these new formulations in terms of efficacy. The lipid-associated amphotericins are significantly less nephrotoxic than conventional amphotericin B, although there are major differences in the infusion-related toxicity of the various lipid-associated preparations. The current armamentarium of azoles and echinocandins for the treatment of invasive mycoses has only left a very minor role for both conventional and lipid-associated amphotericin B in the treatment of a few specific, rare mycoses.

The azole antifungal voriconazole and the echinocandin caspofungin have recently become available for the treatment of invasive mycoses. Fluconazole remains the drug of choice for candidemia, except for infections with one of the resistent species such as Candida krusei and some strains of Candida glabrata. In these cases, as well as in patients who cannot tolerate azoles in connection with side effects or drug interactions, caspofungin is an attractive alternative. Voriconazole has become the drug of choice for severe invasive aspergillosis. Itraconazole is a good alternative for milder and chronic forms of aspergillosis. The use of conventional amphotericin B will be limited by the availability of the new drugs. In view of their high costs, the lipid-bound forms of amphotericin B will usually be given only as salvage therapy in case of failure, in patients who are unable to tolerate either conventional amphotericin or one of the newer agents, and for the treatment of zygomycosis.

The Dutch Health Council recently reported on the scientific desirability of making pneumococcal vaccination available to elderly persons and immunocompromised adults. On the basis of an assessment of the scientific evidence undertaken by the Dutch Cochrane Centre, the Council has concluded that extension of the current indication for pneumococcal vaccination is not scientifically justified. Vaccination is definitely recommended only for patients suffering from asplenia, sickle-cell anaemia or cerebrospinal fluid leakage. Whereas vaccination should be considered in individuals with certain other illnesses, vaccination is not recommended for people of advanced age or those diagnosed with solid tumours, diabetes mellitus, chronic respiratory disease or chronic heart failure.

A 23-year-old Turkish woman was admitted with an infection of the left thumb. The clinical picture was typical for cutaneous anthrax. Microbiological tests confirmed the diagnosis 'infection by Bacillus anthracis'. She recovered when treated with penicillin, although later tests revealed that the bacteria were resistant to this antibiotic. The patient became infected in Belgium as a result of wounding herself on the teeth of an illegally slaughtered sheep, which had possibly become infected in the pasture. Recognising the characteristic clinical picture of cutaneous anthrax is essential for prompt treatment and a favourable prognosis.

Anthrax is a zoonosis which is particularly prevalent in cattle, goats and sheep and is caused by Bacillus anthracis, a Gram-positive spore forming aerobic microorganism. The endospores can survive outside of the body for many decades. The natural form of anthrax has a cutaneous, pulmonary and intestinal form. The pulmonary form can be rapidly fatal but is difficult to recognise due to an initially non-specific, flu-like clinical picture. As a result of spores being inhaled, a mediastinal lymphadenitis arises from which a systemic disease develops with a violent toxaemia, damage to the vascular endothelium, oedema, internal haemorrhages and circulatory collapse. Anthrax is diagnosed by demonstrating the presence of the bacteria in the cutaneous abnormality, in blood or another sterile body component such as cerebrospinal fluid, by means of a direct preparation, immunofluorescence or surface antigens, molecular diagnostics with PCR, or by means of culturing. B. anthracis is sensitive to quinolones, clindamycin and tetracyclines, and often to penicillin. Although naturally acquired cutaneous anthrax can be effectively treated with a short antibiotic cure, it is nevertheless advised in the USA to complete the full 60-day cure and to regard the cutaneous manifestation as a telltale sign of possible respiratory exposure. Anthrax is not transmitted from one person to another.

The Working Party on Antibiotic Policy (Dutch acronym is SWAB) has issued a guideline in which the pro and cons of the routine use of selective decontamination (SD) in patients in intensive care (IC) on mechanical ventilation are compared in order to decide whether SD is indicated. The effectiveness of SD in IC patients was evaluated in 28 prospective, randomized studies. In most studies a significant reduction in the incidence of pneumonia was demonstrated. The incidence of pneumonia in the control groups varied from 5 to 85%. The reduction in the incidence of pneumonia seems to have no effect on duration of mechanical ventilation and IC unit stay or the use of antibiotics. No effect on IC mortality was demonstrated. However, only major reductions could have been demonstrated with the size of the studies carried out so far. A significant reduction of about 20% was suggested in two meta-analyses. The validity of these meta-analyses is questionable. Based on the data available, it is not possible to reach the conclusion that SD will be cost-effective. The size of the studies is too small and the study duration too short to prove that the use of SD, if applied on a large scale, might not eventually lead to development of resistance. Selection of micro-organisms that are already intrinsically resistant or had already acquired resistance to one of the agents used, has been demonstrated. In the absence of clearly demonstrated advantages (decrease in mortality, reduction in the use of antibiotics, cost-effectiveness), the routine use of SD in IC patients on mechanical ventilation is not recommended.

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.

Objective: To determine the drug of choice for the treatment of uncomplicated cystitis., Method: Drug selection was performed by means of the so-called 'system of objectified judgement analysis' (SOJA) method by a working group of 11 persons. The following selection criteria were used: pharmacokinetics, interactions, probability of hitting (the probability that the microorganism is sensitive to the antibiotic), development of resistance, specific use in urinary tract infections, efficacy, side effects, dosage-frequency, duration of treatment, cost and documentation. The following drugs were included in the study: amoxicillin (with or without clavulanic acid), nitrofurantoin, sulfamethizole, trimethoprim, co-trimoxazole, ciprofloxacin, norfloxacin, ofloxacin and fosfomycin trometamol., Results: Fosfomycin and nitrofurantoin slow release showed the highest scores. The main selection criteria that determined the selection of a drug were especially specific use in urinary tract infections, development of resistance, probability of hitting and cost., Conclusion: Fosfomycin and nitrofurantoin slow release best fulfill the requirements for drugs in the treatment of uncomplicated cystitis. No comparative studies have been performed with the 3-day treatment of uncomplicated cystitis with nitrofurantoin slow release or with trimethoprim. Fluoroquinolones play no important part in the treatment of uncomplicated cystitis, mainly because of the risk of development of resistance.

Major reasons to conduct antibiotic policies are to improve the quality of patient care, to limit the emergence of resistance, and to contain costs. Many studies have addressed overconsumption and misuse of antibiotics. Studies have shown a correlation between antibiotic use in hospitals and the development of microbial resistance. Recommendations for the content and management of future antibiotic policy strategies in hospitals include educational programmes, consultation by infectious diseases physicians, restriction of the formulary, timely narrowing of empirical broad spectrum therapy ('streamlining'), and automatic stop orders. A recent study in a Dutch university hospital revealed overconsumption of antibiotics for prophylaxis in surgery and undertreatment with antibiotics in internal medicine departments. Intervention resulted in better compliance with guidelines, reduction of the consumption of antibiotics in surgical prophylaxis, and cost containment. However optimation of antimicrobial therapy also sometimes resulted in an increase of antimicrobial drug consumption.

Cytokines are essential mediators in infection and inflammation. Almost all cytokines have not only positive but also noxious effects: the proinflammatory cytokines released during severe infections in high concentrations lead to organ damage and death. The antagonistic anti-inflammatory cytokines inhibit the defense against infections. Immunotherapy through modulation of the cytokine response may aim at inhibition of the proinflammatory and reinforcement of the anti-inflammatory cytokine response, so as to limit the damage of inflammation. In patients with sepsis this has so far been little successful, probably owing to the multiple effects of the cytokines. Inhibition of proinflammatory cytokines was successful, on the other hand, in patients with rheumatoid arthritis or Crohn's disease. Another possibility is to aim, on the contrary, at reinforcement of the proinflammatory and inhibition of the anti-inflammatory cytokine response, to strengthen the resistance of the host. This has given favourable results in a limited number of infections.

Since the mid-eighties an increase of severe infections with invasive group A streptococci (GAS) has been noticed throughout the world, not only in the elderly but in healthy adults as well. The acute presenting infection starts with fever, enanthema, generalised erythema, rapidly progressing into shock and multiorgan failure, and is called streptococcal toxic shock syndrome (STSS). Despite surgical and antibiotic therapy with penicillin and clindamycin the mortality is high. There are as yet insufficient data in patients with STSS to decide between penicillin en clindamycin. Intravenous administration of high dose gammaglobulin, advocated in the USA, might neutralize the exotoxins, but the effectiveness of this therapy has not been established yet.

The problem of international spread of bacterial resistance requires development of a strategy at worldwide or at least at European level. Clinically relevant monitoring systems for resistance and use of antibiotics have to be implemented to support the guidelines on prescription of antibiotics. Every hospital should establish an 'antibiotics team' controlling the prescription of antimicrobials and the observance of local formulary agreements. Veterinary use of growth promoting antimicrobials related to substances used in human medicine should be terminated. Future research should be aimed at resolving the problem of resistance to antimicrobials.

A previously healthy 44-year-old male traveller presented with a dry cough, fever and an abnormal chest X-ray after a stay in Guatemala, where he had explored bat caves. Acute pulmonary histoplasmosis was diagnosed after culture of Histoplasma capsulatum from bronchial washings. A favourable response was seen upon treatment with itraconazole for six weeks. Acute pulmonary histoplasmosis should be considered in a healthy traveller returning with fever from the USA or subtropical areas.

The incidence of invasive infections with Candida has strongly increased during the last few decades. Candida is now one of the commonest hospital pathogens. Many infections are nowadays caused by other species than C. albicans, notably C. tropicalis, C. krusei and C. glabrata. Particularly in HIV seropositive patients the yeast may develop resistance to fungistatic drugs. The altered species frequency and the resistance appear to be caused by the use of fungistatic agents of the imidazole group. To counter these developments the choice of antifungal therapeutics should be made very carefully.