Decontamination of the digestive tract and oropharynx in ICU patients.

BACKGROUND: Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) are infection-prevention measures used in the treatment of some patients in intensive care, but reported effects on patient outcome are conflicting. METHODS: We evaluated the effectiveness of SDD and SOD in a crossover study using cluster randomization in 13 intensive care units (ICUs), all in The Netherlands. Patients with an expected duration of intubation of more than 48 hours or an expected ICU stay of more than 72 hours were eligible. In each ICU, three regimens (SDD, SOD, and standard care) were applied in random order over the course of 6 months. Mortality at day 28 was the primary end point. SDD consisted of 4 days of intravenous cefotaxime and topical application of tobramycin, colistin, and amphotericin B in the oropharynx and stomach. SOD consisted of oropharyngeal application only of the same antibiotics. Monthly point-prevalence studies were performed to analyze antibiotic resistance. RESULTS: A total of 5939 patients were enrolled in the study, with 1990 assigned to standard care, 1904 to SOD, and 2045 to SDD; crude mortality in the groups at day 28 was 27.5%, 26.6%, and 26.9%, respectively. In a random-effects logistic-regression model with age, sex, Acute Physiology and Chronic Health Evaluation (APACHE II) score, intubation status, and medical specialty used as covariates, odds ratios for death at day 28 in the SOD and SDD groups, as compared with the standard-care group, were 0.86 (95% confidence interval [CI], 0.74 to 0.99) and 0.83 (95% CI, 0.72 to 0.97), respectively. CONCLUSIONS: In an ICU population in which the mortality rate associated with standard care was 27.5% at day 28, the rate was reduced by an estimated 3.5 percentage points with SDD and by 2.9 percentage points with SOD. (Controlled Clinical Trials number, ISRCTN35176830.)

[Preventing prolonged antibiotic therapy by active implementation of switch guidelines]. / Onnodig lange intraveneuze antibioticatherapie voorkomen door actieve implementatie van switchrichtlijnen.

OBJECTIVE: To reduce the number of days of unnecessary intravenous antibiotic therapy via an early switch to oral antibiotic therapy. DESIGN: Prospective, open trial. METHODS: A guideline was drawn up for an early and yet safe switch from intravenous to oral antibiotic therapy. Patients on the wards of Internal Medicine, Pulmonology, Surgery and Orthopaedics of the Haaglanden Medical Centre in The Hague, the Netherlands, were followed for four months. A zero measurement at two months was followed by an intervention period of two months. The number of unnecessary days of intravenous antibiotic therapy was taken as the measure of effectiveness. A multidisciplinary team carried out the interventions, consisting of educational, supportive and guiding measures. Making progress measurable and giving feedback played an important role during the intervention. RESULTS: During the zero-measurement period on the Internal Medicine and Pulmonology wards, 26% (9/35) of patients were switched within the timeframe predefined by the guideline. The average number of unnecessary i.v. days was 2.4 (median: 2). During the intervention period, 84% (64/76) were switched within the predefined timeframe, with an average of 0.2 unnecessary i.v. days per patient (median: 0). There was thus a significantly lower number of unnecessary i.v. days after intervention (difference: 2.2; 95%-CI: 1.5-3.0). On the surgical and orthopaedic wards, 9% (2/22) of patients were switched within the predefined timeframe during the zero-measurement period, with an average of 7.3 unnecessary i.v. days (median: 5). During the intervention period, 52% of patients (17/33) were switched within the predefined timeframe, for an average of 1.1 unnecessary i.v. days (median: 0). The reduction in the number of unnecessary i.v. days was also significant here (difference: 6.2; 95%-CI: 2.9-9.5). CONCLUSION: A significant reduction in the number of unnecessary days of intravenous antibiotic therapy was obtained via simple interventions carried out by a multidisciplinary team.

Guidelines for detection of penicillin tolerance in Streptococcus pyogenes by MIC-MBC method.

Disagreement on a uniform and accepted method of testing penicillin tolerance in Streptococcus pyogenes prevents a meaningful comparison of results of various studies on tolerance and an assessment of the contribution of this phenomenon to treatment failure. Therefore guidelines are needed.

Penicillin tolerance and treatment failure in group A streptococcal pharyngotonsillitis.

Failure of treatment of group A streptococcal pharyngitis and tonsillitis is well documented. One of the possible explanations for treatment failure is penicillin tolerance in group A streptococci. Reports on the prevalence of penicillin tolerance among group A streptococci (0-100%) and the presumed relationship with therapeutic failure vary considerably. Therefore, it appears worthwhile to review pharyngotonsillitis studies, devoting special attention to the variables of MIC-MBC laboratory determinations such as inoculum preparation, composition and volume of test medium, and the criteria used to define penicillin tolerance. Alternative methods (gradient-replica plate method, beta-lactamase disk test, time-kill assay, and cell-lysis assay) are discussed. It is concluded that technical factors and the definitions used influenced the reported rates of penicillin tolerance. The epidemiological data suggest that tolerance is not limited to a single streptococcal serotype. Furthermore, there is not sufficient data to support a correlation between in vitro penicillin tolerance of group A streptococci and treatment failure, either in clinical cases or in animal studies. On the other hand, evidence to exclude penicillin tolerance as a cause of treatment failure is also not available. Therefore, at present penicillin tolerance cannot be ruled out as a cause of penicillin treatment failures.

Susceptibility of Streptococcus pyogenes to azithromycin, clarithromycin, erythromycin and roxithromycin in vitro.

The susceptibility of 180 clinical isolates of Streptococcus pyrogenes from six regions of The Netherlands to the macrolide antibiotics azithromycin, clarithromycin, erythromycin and roxithromycin was analysed. The results of a microbroth MIC method, the E-test method and a disk diffusion assay were compared, and the MBC determined. In addition, the susceptibility to erythromycin of 436 clinical isolates of S. pyogenes from the Leiden region was determined. The microbroth MIC90s of azithromycin, clarithromycin, erythromycin and roxithromycin for group A streptococci were < or = 0.5 mg/L. Erythromycin had the lowest MIC90 (0.09 mg/L). The MIC data obtained with the E-test method suggested that clarithromycin and erythromycin had slightly higher anti-streptococcal activity than azithromycin and roxithromycin in vitro. MICs obtained with the E-test were lower than those found with the microbroth method. Only minor discrepancies were observed among the three methods. The MBC50 for both clarithromycin and erythromycin was 0.75 mg/L and 5.0 mg/L for azithromycin and roxithromycin. None of the 180 strains and two of the collection of 436 strains (0.5%) were resistant to erythromycin and the other macrolides tested; MICs ranged from 1 to 16 mg/L. The erythromycin-resistant strains showed an inducible type of macrolide-lincosamide-streptogramin B (MLS) resistance.

Enterococcus faecalis colonisation and endocarditis in five intensive care patients as late sequelae of selective decontamination.

OBJECTIVE: To describe Enterococcus faecalis colonisation and endocarditis in 5 intensive care patients after treatment with selective decontamination (SDD). SETTING: Intensive care unit (ICU) in a general hospital. PATIENTS: The patients were admitted to the ICU because of adult respiratory distress syndrome, polytrauma (2 patients), abdominal aortic surgery and gastrointestinal surgery. Because these patients needed mechanical ventilation they received systemic cefotaxime and SDD (polymyxin E, amphotericin B and norfloxacin). RESULTS: Colonisation with E. faecalis was documented in all patients. Intravascular catheter-related infection with E. faecalis occurred in 4 patients. None of the patients received antibiotics active against, E. faecalis, because body temperature normalised after catheter removal. In the course of his ICU stay one patient died. Autopsy showed E. faecalis endocarditis. The other 4 patients recovered from their primary illness, but had to be readmitted after several months because of E. faecalis endocarditis. One of these patients died. One patient recovered of endocarditis, but one year later valve surgery was necessary. The other 2 patients needed acute valve replacement. The latter 3 patients survived. CONCLUSION: We observed 5 patients with E. faecalis endocarditis as a late and severe sequela of SDD during their ICU stay.

Differences in penicillin-binding protein patterns of penicillin tolerant and non-tolerant group A streptococci.

The penicillin-binding proteins (PBPs) of five penicillin tolerant group A streptococci and their isogenic non-tolerant strains, and seven unrelated non-tolerant group A streptococci were compared. PBPs from late logarithmic cultures were labelled in vitro with 3H-benzylpenicillin and analysed by SDS-PAGE and fluorography. The PBP patterns for all non-tolerant strains were identical. This pattern differed markedly from that for penicillin tolerant strains, both qualitatively and quantitatively. The most striking change in penicillin tolerant strains was decreased binding of 3H-penicillin to PBP 3 and increased binding to PBP 5, while PBP 2a was replaced by a new PBP (PBP 2a') of lower electrophoretic mobility. Tolerance was lost during storage but could be restored by consecutive transfers on to penicillin gradient agar plates. At the same time the PBP profiles of these strains became identical to those found for stable tolerant strains. These results suggest the possibility that PBP 2a' and PBP 5 in combination with other PBP alterations play a role in penicillin tolerance found in group A streptococci.

Detection of penicillin tolerance in Streptococcus pyogenes.

Three traditional assays were used to determine the minimal bactericidal concentration (MBC) and minimal inhibitory concentration (MIC) for Streptococcus pyogenes (group A streptococci) in two phases of growth and the time taken to kill the organisms. Three other methods were used for the determination of penicillin tolerance: a cell-lysis assay, the beta-lactamase disk method and the replication method. Twenty strains, comprising penicillin-tolerant clinical isolates and two laboratory mutants, were used to evaluate the six tests. Results indicated that two groups of S. pyogenes can be distinguished--four highly tolerant and three moderately tolerant strains. The moderately tolerant strains were not recognised when rapidly growing instead of stationary cultures were used for the MBC and MIC determinations. The MBC/MIC ratio for tolerant strains was > 100. Tolerance percentage ranged from 0.30 to 1.07 and 0.29 to 3.96 for cultures in the mid-logarithmic and stationary phases of growth, respectively. The cell-lysis assay, the beta-lactamase disk method and the replication method may be used to screen for tolerance. Detection of high or moderate tolerance by determining the MBC/MIC ratio for mid-logarithmic or stationary cultures is recommended.

High-level aminoglycoside resistance among enterococci and group A streptococci.

The occurrence of high-level aminoglycoside resistance (HLAmR) was determined for 73 enterococci and 54 group A streptococci by the high-load disc method, tube macrodilution and the polymerase chain reaction (PCR). The PCR method revealed the presence of genes coding for aminoglycoside-3'-O-phosphoryltransferase-III (APH(3')-III), aminoglycoside-6'-N-acetyltransferase/2''-O-phosphoryltransferase (AAC(6')/APH(2'')), or both, in 20.6%, 9.6% and 4.1% of the enterococci, respectively. The prevalence of HLAmR to at least one aminoglycoside among local enterococci was 37% (27/73). Only one of 54 Streptococcus pyogenes isolates produced APH(3')-III and exhibited high-level resistance to kanamycin and streptomycin. In general, the three methods yielded comparable results, with only three discrepancies among the 127 isolates examined. High-load disc screening and tube macrodilution proved to be practical, reliable and reproducible, and thus suitable for routine screening. Of 20 Enterococcus faecalis strains tested, all were penicillin-tolerant. Only one of seven penicillin-tolerant S. pyogenes strains was HLAmR. No association between the two forms of resistance was found.

Serous otitis media (S.O.M.). A bacteriological study of the ear canal and the middle ear.

A bacteriological study of the middle-ear effusions and the ear canals in children with chronic serous otitis media (S.O.M.) was performed. Sixty-eight children (127 ears) were investigated. From this study it appeared that cleansing of the ear canal with 0.5% chlorhexidine in 70% ethanol for 30 s is partially effective; micro-organisms (diptheroids, Staphylococcus epidermidis) could still be isolated in 29%. Cleansing of the ear canal decreases the incidence of middle-ear fluid contamination by non-pathogenic ear canal organisms (diptheroids, Staphylococcus epidermidis, Aerococcus), but after cleansing, 'non-pathogenic' micro-organisms could still be isolated in 33% of the effusions (diptheroids, Staphylococcus epidermidis). From 12% of the middle-ear effusions pathogenic micro-organisms (Hemophilus influenzae, Staphylococcus pneumoniae) were isolated; cleansing of the ear canal did not influence this percentage. Anaerobics were not isolated from the middle-ear effusions.