Peterhans J. van den Broek

Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind study

Abstract Objective To compare the effectiveness of discontinuing treatment with amoxicillin after three days or eight days in adults admitted to hospital with mild to moderate-severe community acquired pneumonia who substantially improved after an initial three days treatment. Design Randomised, double blind, placebo controlled non-inferiority trial. Setting Nine secondary and tertiary care hospitals in the Netherlands. Participants Adults with mild to moderate-severe community acquired pneumonia (pneumonia severity index score ≤ 110). Interventions Patients who had substantially improved after three days treatment with intravenous amoxicillin were randomly assigned to oral amoxicillin (n = 63) or placebo (n = 56) three times daily for five days. Main outcome measures The primary outcome measure was the clinical success rate at day 10. Secondary outcome measures were the clinical success rate at day 28, symptom resolution, radiological success rates at days 10 and 28, and adverse events. Results Baseline characteristics were comparable, with the exception of symptom severity, which was worse in the three day treatment group. In the three day and eight day treatment groups the clinical success rate at day 10 was 93% for both (difference 0.1%, 95% confidence interval − 9% to 10%) and at day 28 was 90% compared with 88% (difference 2.0%, − 9% to 15%). Both groups had similar resolution of symptoms. Radiological success rates were 86% compared with 83% at day 10 (difference 3%, − 10% to 16%) and 86% compared with 79% at day 28 (difference 6%, − 7% to 20%). Six patients (11%) in the placebo group and 13 patients (21%) in the active treatment group reported adverse events (P = 0.1). Conclusions Discontinuing amoxicillin treatment after three days is not inferior to discontinuing it after eight days in adults admitted to hospital with mild to moderate-severe community acquired pneumonia who substantially improved after an initial three days treatment.

Do Biofilm Formation and Interactions with Human Cells Explain the Clinical Success of Acinetobacter baumannii

Background The dramatic increase in antibiotic resistance and the recent manifestation in war trauma patients underscore the threat of Acinetobacter baumannii as a nosocomial pathogen. Despite numerous reports documenting its epidemicity, little is known about the pathogenicity of A. baumannii. The aim of this study was to obtain insight into the factors that might explain the clinical success of A. baumannii. Methodology/Principal Findings We compared biofilm formation, adherence to and inflammatory cytokine induction by human cells for a large panel of well-described strains of A. baumannii and compared these features to that of other, clinically less relevant Acinetobacter species. Results revealed that biofilm formation and adherence to airway epithelial cells varied widely within the various species, but did not differ among the species. However, airway epithelial cells and cultured human macrophages produced significantly less inflammatory cytokines upon exposure to A. baumannii strains than to strains of A. junii, a species infrequently causing infection. Conclusion/Significance The induction of a weak inflammatory response may provide a clue to the persistence of A. baumannii in patients.

Eradication of carriage with methicillin-resistant Staphylococcus aureus: effectiveness of a national guideline

BACKGROUNDnWe evaluated the effectiveness of eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage in the Netherlands after the introduction of a guideline in 2006. The guideline distinguishes complicated (defined as the presence of MRSA infection, skin lesions, foreign-body material, mupirocin resistance and/or exclusive extranasal carriage) and uncomplicated carriage (not meeting criteria for complicated carriage). Mupirocin nasal ointment and chlorhexidine soap solution are recommended for uncomplicated carriers and the same treatment in combination with two oral antibiotics for complicated carriage.nnnMETHODSnA prospective cohort study was performed in 18 Dutch centres from 1 October 2006 until 1 October 2008.nnnRESULTSnSix hundred and thirteen MRSA carriers underwent one or more decolonization treatments during the study period, mostly after hospital discharge. Decolonization was achieved in 367 (60%) patients with one eradication attempt and ultimately 493 (80%) patients were decolonized, with a median time until decolonization of 10 days (interquartile range 7-43 days). Three hundred and twenty-seven (62%) carriers were treated according to the guideline, which was associated with an absolute increase in treatment success of 20% [from 45% (91/203) to 65% (214/327)].nnnCONCLUSIONSnSixty percent of MRSA carriers were successfully decolonized after the first eradication attempt and 62% were treated according to the guideline, which was associated with an increased treatment success.

Eradication of carriage with methicillin-resistant Staphylococcus aureus: determinants of treatment failure

BACKGROUNDnUsing data from an observational study in which the effectiveness of a guideline for eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage was evaluated, we identified variables that were associated with treatment failure.nnnMETHODSnA multivariate logistic regression model was performed with subgroup analyses for uncomplicated and complicated MRSA carriage (the latter including MRSA infection, skin lesions, foreign-body material, mupirocin resistance and/or exclusive extranasal carriage) and for those treated according to the guideline (i.e. mupirocin nasal ointment and chlorhexidine soap solution for uncomplicated carriage, in combination with two oral antibiotics for complicated carriage).nnnRESULTSnSix hundred and thirteen MRSA carriers were included, of whom 333 (54%) had complicated carriage; 327 of 530 patients (62%) with known complexity of carriage were treated according to the guideline with an absolute increase in treatment success of 20% (95% confidence interval 12%-28%). Among those with uncomplicated carriage, guideline adherence [adjusted odds ratio (OR(a)) 7.4 (1.7-31.7)], chronic pulmonary disease [OR(a) 44 (2.9-668)], throat carriage [OR(a) 2.9 (1.4-6.1)], perineal carriage [OR(a) 2.2 (1.1-4.4)] and carriage among household contacts [OR(a) 5.6 (1.2-26)] were associated with treatment failure. Among those with complicated carriage, guideline adherence was associated with treatment success [OR(a) 0.2 (0.1-0.3)], whereas throat carriage [OR(a) 4.4 (2.3-8.3)] and dependence in activities of daily living [OR(a) 3.6 (1.4-8.9)] were associated with failure.nnnCONCLUSIONSnGuideline adherence, especially among those with complicated MRSA carriage, was associated with treatment success. Adding patients with extranasal carriage or dependence in daily self-care activities to the definition of complicated carriage, and treating them likewise, may further increase treatment success.

Three-Dimensional Human Skin Equivalent as a Tool To Study Acinetobacter baumannii Colonization

ABSTRACT Acinetobacter baumannii can colonize body surfaces of hospitalized patients. From these sites, invasion into the host and spread to other patients and the hospital environment may occur. The eradication of the organism from the patients skin is an important infection control strategy during epidemic and endemic episodes. In this study, a three-dimensional (3D), air-exposed human epidermal skin equivalent was exploited to study Acinetobacter skin colonization. We characterized the adherence of A. baumannii ATCC 19606T and Acinetobacter junii RUH2228T to and biofilm formation on the skin equivalent and the responses to these bacteria. Furthermore, we assessed the ability of the disinfectant chlorhexidine to decolonize the skin equivalents. The results revealed that both strains replicated on the stratum corneum for up to 72 h but did not invade the epidermis. A. baumannii, in contrast to A. junii, formed large biofilms on the stratum corneum. Bacterial colonization did not affect keratinocyte activation, proliferation, or differentiation, nor did it induce a strong inflammatory response. Disinfection with chlorhexidine solution resulted in complete eradication of A. baumannii from the skin, without detrimental effects. This 3D model is a promising tool to study skin colonization and to evaluate the effects of novel disinfectant and antimicrobial strategies.

Appropriate use of indwelling urethra catheters in hospitalized patients: results of a multicentre prevalence study

BackgroundAlthough indwelling urethra catheterization is a medical intervention with well-defined risks, studies show that approximately 14–38% of the indwelling urethra catheters (IUCs) are placed without a specific medical indication. In this paper we describe the prevalence of IUCs, including their inappropriate use in the Netherlands. We also determine factors associated with inappropriate use of IUCs in hospitalized patients.MethodsIn 28 Dutch hospitals, prevalence surveys were performed biannually in 2009 and 2010 within the PREZIES-network. All patients admitted to a participating hospital and who had an IUC in place at the day of the survey were included. Pre-determined criteria were used to categorize the indication for catheterization as appropriate or inappropriate.ResultsA total of 14,252 patients was included and 3020 (21.2%) of them had an IUC (range hospitals 13.4-27.3). Initial catheter placement was inappropriate in 5.2% of patients and 7.5% patients had an inappropriate indication at the day of the survey. In multivariate analyses inappropriate catheter use at the time of placement was associated with female sex, older age, admission on a non-intensive care ward, and not having had surgery. Inappropriate catheter use at the time of survey showed comparable associated factors.ConclusionsAlthough lower than in many other countries, inappropriate use of IUC is present in Dutch hospitals. To reduce the inappropriate use of IUCs, recommended components of care (bundle for UTI), including daily revision and registration of the indication for catheterization, should be introduced for all patients with an IUC. Additionally, an education and awareness campaign about appropriate indications for IUC should be available.

Cross-sectional study of availability and pharmaceutical quality of antibiotics requested with or without prescription (Over The Counter) in Surabaya, Indonesia.

BackgroundAntimicrobial resistance is an increasing problem in developing countries and antibiotic use is widespread. Our previous surveys in Java, Indonesia, revealed that most antibiotic use was probably unnecessary or ineffective. The aim of this study was to explore a potential connection between resistance and substandard antibiotics sold in the area.MethodsA cross-sectional field study using the simulated client method was conducted in Surabaya. Five first-line antibiotics were requested with or without prescription (OTC). A certified laboratory analysed the drug content using validated methods. Possible determinants of substandard quality were explored.ResultsIn total, 104 samples from 75 pharmacies, ten drug stores and 39 roadside stalls (kiosks) were obtained. Pharmacy employees filled all OTC requests. Three quarters of kiosks sold antibiotics. Antibiotics were dispensed as single blister strips or repackaged (16%) without label. Ninety five percent of samples carried the label of 14 Indonesian manufacturers. The pharmaceutical quality did not meet BP standards for 18% of samples. Deviations (less active ingredient) were small. There was no association between low content and type of outlet, sold with or without prescription, registration type, price or packaging. Median retail prices of products carrying the same label varied up to 20 fold.ConclusionsAntibiotics were available OTC in all visited pharmacies and sold in the streets of an Indonesian city. Most samples contained an active ingredient. We urge to increase enforcement of existing regulations, including legislation that categorizes antibiotics as prescription-only drugs for all types of medicine outlets, to limit further selection of antimicrobial resistance.

Determinants of carriage of resistant Staphylococcus aureus among S. aureus carriers in the Indonesian population inside and outside hospitals.

Objectivesu2002 To identify determinants of carriage of resistant Staphylococcus aureus in both hospitalized patients and individuals from the community in two urban centres in Indonesia.

Optimizing antibiotic usage in adults admitted with fever by a multifaceted intervention in an Indonesian governmental hospital

Objectiveu2002 To optimize antimicrobial treatment of patients with fever upon admission to the department of internal medicine of Dr Soetomo Hospital in Surabaya, Indonesia.

How much time should long-term care and geriatric rehabilitation facilities (nursing homes) spend on infection control?

BACKGROUNDnFor hospitals, standards for the required number of infection control personnel are outdated and disputed. Such standards are not even available for long-term care and geriatric rehabilitation facilities (ie, nursing homes). This study addressed the question of how much time nursing homes should spend on infection control.nnnMETHODSnThrough group discussions and individual sessions, experienced infection control practitioners, medical microbiologists, and nursing home doctors evaluated the time needed to perform infection control activities in a model nursing home.nnnRESULTSnThe number of hours needed was estimated as 513 per 100 beds, or 154 per 10,000 care-days per year.nnnCONCLUSIONnGiven that significant differences can be expected among the various facilities identified as nursing homes, long-term care facilities, or geriatric rehabilitation centers, as well as among countries, the standard that we propose for The Netherlands will not be generally applicable. However, the method we have used to determine this standard can be easily applied in other countries and settings.