Modified guidelines impact on antibiotic use and costs: duration of treatment for pneumonia in a neurosurgical ICU is reduced.

OBJECTIVES: To evaluate the impact of an intervention to reduce the duration of antibiotic treatment for pneumonia in a neurosurgical intensive care unit (ICU). The usage of antibiotics and the resultant costs were examined using interrupted time series analysis while resistance and device-associated infection rates are also described. METHODS: In January 2004, revised guidelines for the use of antibiotics were implemented. As a consequence of this, the duration of antibiotic therapy for nosocomial pneumonia was reduced from 14 to 7 days, while for community-acquired pneumonia the period fell from 10 to 5 days. The effect on the antibiotic use density [AD; expressed as defined daily doses (DDD) per 1000 patient days (pd)] was calculated by segmented regression analysis of interrupted time series for the 24 months prior to (2002 and 2003) and after the intervention (2004 and 2005). RESULTS: The intervention was associated with a significant decrease in total AD from 949.8 to 626.7 DDD/1000 pd after the intervention. This was mainly due to reduced consumption of second-generation cephalosporins (-100.6 DDD/1000 pd), imidazoles (- 100.3 DDD/1000 pd), carbapenems (-33.3 DDD/1000 pd), penicillins with beta-lactamase inhibitor (-33.5 DDD/1000 pd) and glycopeptides (-30.2 DDD/1000 pd). Glycopeptide reduction might be associated with a significant decrease in the proportion of methicillin-resistant Staphylococcus aureus (8.4% before and 2.9% after the intervention). Similarly, total antibiotic costs/pd (Euro) showed a significant decrease from 13.16 Euro/pd before to 7.31 euro/pd after the intervention. This is a saving of 5.85 Euro/pd. The incidence of patients dying with pneumonia did not change significantly. CONCLUSIONS: The most conservative estimate of segmented regression analysis over a 48 month period showed that halving the duration of treatment for pneumonia results in a reduction of over 30% in antibiotic consumption and costs. Because respiratory infections are most common in ICU patients, interventions targeting a reduction in the duration of treatment of pneumonia might be extremely worthwhile.

Extract of Pelargonium sidoides (EPs 7630) inhibits the interactions of group A-streptococci and host epithelia in vitro.

EPs 7630 is an extract of the root of the South African geranium Pelargonium sidoides. Clinical data have shown that this herbal drug preparation can be used to treat upper respiratory tract infections (URTI). The objective of this study was to investigate the impact of EPs 7630 on group A-streptococci (GAS) adhering to and invading host epithelial cells in vitro. Adhesion was assessed by a flow cytometric adhesion assay using calcein-AM-stained S. pyogenes (DSM 2071) as test organism, and HEp-2 cells and buccal epithelial cells (BEC) as substrata. For cell invasion, HEp-2 cell monolayers were infected with S. pyogenes. Intracellular bacteria were determined using a penicillin/gentamicin-protection assay. EPs 7630 was applied in therapeutically relevant concentrations between 0 and 30 microg/ml in both test systems. Compared to controls, EPs 7630 significantly reduced GAS adhesion to HEp-2 cells in a concentration-dependent manner by up to 46% (p<0.001). This was semi-quantitatively confirmed by fluorescence microscopy. Adhesion kinetics additionally indicated a specific antagonistic effect on GAS adhesion. Pre-treatment of epithelial cells or GAS with EPs 7630 showed that it targets GAS rather than HEp-2 cells. However when using BEC as substrata, GAS adhesion increased 7-fold under the influence of EPs 7630 (p<0.001). In viability assays, HEp-2 suspension contained over 90% vital cells, whereas only 10% of the BEC were viable. EPs 7630 reduced GAS invasion of HEp-2 cells significantly when the data taken at time points 60, 120, and 180 min (p=0.026) were analyzed. In conclusion, EPs 7630 develops complementary anti-infective properties: Firstly, EPs 7630 reduces bacterial adhesion to intact epithelial cells and thus protects the organism from bacterial colonization and infection/super-infection. Secondly, EPs 7630 enhances the attachment of bacteria to decaying BEC. In this way pathogens may be trapped and rendered inactive. Thirdly, the inhibition of GAS invasion of epithelial cells protects the host from microorganisms that may have evaded host defences and antibiotic treatment, and therefore prevents recurrent infections. Thus, our investigations provide a rational basis for the treatment of URTI with EPs 7630.

Extract of Pelargonium sidoides (EPs 7630) improves phagocytosis, oxidative burst, and intracellular killing of human peripheral blood phagocytes in vitro.

Clinical data show that EPs 7630, an aqueous ethanolic extract from the roots of Pelargonium sidoides, can be used for the treatment of upper respiratory tract infections (URTI). The biological effects of the preparation have not been fully investigated. The objective of this study was to examine the impact of EPs 7630 on the activity of human peripheral blood phagocytes (PBP). A whole blood-based, flow cytometric assay was used to simultaneously assess phagocytosis and oxidative burst. Calcein-AM stained Candida albicans (DSM 1386) were used as target organisms. Oxidative burst was measured by addition of dihydroethidium (DHE). Target organisms and whole blood were co-incubated and analyzed after 0, 2, 4, 6, 10, and 30 min. Intracellular killing of the target organisms was evaluated by determining the number of surviving yeast cells after co-incubation of C. albicans and human whole blood. EPs 7630 was applied in therapeutically relevant concentrations between 0 and 30 microg/ml. Compared with controls EPs 7630 increased the number of phagocytosing PBP during the observed time points between 2 and 10 min in a concentration-dependent manner, with a maximum enhancement of 56% at 2 min (p=0.002). The application of EPs 7630 also led to a significant increase in the number of burst-active PBP for all time points observed beyond 2 min (p<0.001). The maximum augmentation was 120% after application of 30 microg/ml EPs 7630 at 4 min. Using a microbiological assay, intracellular killing was also enhanced by EPs 7630. This was expressed by a significant reduction in the number of surviving target organisms (p<0.001). The maximum reduction in viable yeast cells (-31%) was observed after co-incubation for 120 min with the highest concentration of EPs 7630 (30 microg/ml). In conclusion, the positive effects of EPs 7630 on phagocytosis, oxidative burst, and intracellular killing of yeast cells as test organisms are important components of the compound's biological activity. Our findings constitute a valuable contribution to understanding the clinical effects of EPs 7630.

Methicillin-resistant Staphylococcus aureus in German intensive care units during 2000-2003: data from Project SARI (Surveillance of Antimicrobial Use and Antimicrobial Resistance in Intensive Care Units).

OBJECTIVES: The objective of this study was to analyze methicillin-resistant Staphylococcus aureus (MRSA) percentages (defined as the percentage of S. aureus isolates that are resistant to methicillin) and antimicrobial consumption in intensive care units (ICUs) participating in Project SARI (Surveillance of Antimicrobial Use and Antimicrobial Resistance in Intensive Care Units), to look for temporal changes in MRSA percentages and antimicrobial consumption in individual ICUs as an indicator of the impact of an active surveillance system, and to investigate the differences between ICUs with increased MRSA percentages versus those with decreased percentages during a period of 3 years (2001-2003). METHODS: This was a prospective, ICU-based and laboratory-based surveillance study involving 38 German ICUs during 2000-2003. Antimicrobial use was reported in terms of defined daily doses (DDDs) per 1,000 patient-days. Temporal changes in the MRSA percentage and antimicrobial use in individual ICUs were calculated by means of the Wilcoxon signed rank test. The incidence density of nosocomial MRSA infection was defined as the number of nosocomial MRSA infections per 1,000 patient-days. RESULTS: From February 2000 through December 2003, a total of 38 ICUs reported data on 499,694 patient-days and 9,552 S. aureus isolates, including 2,249 MRSA isolates and 660,029 DDDs of antimicrobials. Cumulative MRSA percentages ranged from 0% to 64.4%, with a mean of 23.6%. The MRSA incidence density ranged from 0 to 38.2 isolates per 1,000 patient-days, with a mean of 2.77 isolates per 1,000 patient-days. There was a positive correlation between MRSA percentage and imipenem and ciprofloxacin use (P<.05). Overall, comparison of data from 2001 with data from 2003 showed that MRSA percentages increased in 18 ICUs (median increase, 13.2% [range, 1.6%-38.4%]) and decreased in 14 ICUs (median decrease, 12% [range, 1.0%-48.4%]). Increased use of third-generation cephalosporins, glycopeptides, or aminoglycosides correlated significantly with an increase in the MRSA percentage (P<.05). The cumulative nosocomial MRSA infection incidence density for 141 ICUs that did not participate in SARI and, therefore, did not receive feedback increased from 0.26 to 0.35 infections per 1,000 patient-days during a 3-year period, whereas the rate in SARI ICUs decreased from 0.63 to 0.40 infections per 1,000 patient-days. CONCLUSION: The MRSA situation in German ICUs is still heterogeneous. Because MRSA percentages range from 0% to 64.4%, further studies are required to confirm findings that no change in the MRSA percentage and a decrease in the nosocomial MRSA infection incidence density in SARI ICUs reflect the impact of an active surveillance system.

Plasmid-mediated quinolone resistance in isolates obtained in german intensive care units.

Screening of 703 isolates of Enterobacteriaceae, obtained from 34 German intensive care units (ICUs), revealed qnr-positive, integron-containing isolates of Enterobacter sp. and Citrobacter freundii from four patients in 2 German ICUs. This is one of the first reports of qnr-positive strains obtained from patients in Europe.

Does disinfection of environmental surfaces influence nosocomial infection rates? A systematic review.

OBJECTIVE: To review the evidence on the effects of disinfection of environmental surfaces in hospitals (as compared with cleaning without use of disinfectants) on the occurrence of nosocomial infections. METHODS: Systematic review of experimental and nonexperimental intervention studies dealing with environmental disinfection or cleaning in different health care settings. RESULTS: A total of 236 scientific articles were identified. None described a meta-analysis, systematic review, or randomized controlled trial. Only 4 articles described completed cohort studies matching the inclusion criteria. None of these studies showed lower infection rates associated with routine disinfection of surfaces (mainly floors) versus cleaning with detergent only. CONCLUSIONS: Disinfectants may pose a danger to staff, patients, and the environment and require special safety precautions. However, targeted disinfection of certain environmental surfaces is in certain instances an established component of hospital infection control. Given the complex, multifactorial nature of nosocomial infections, well-designed studies that systematically investigate the role of surface disinfection are required.

Pathogen growth in herbal teas used in clinical settings: a possible source of nosocomial infection?

In some clinical settings, herbal tea is used in patient care (eg, for oral hygiene). Teabags containing herbal tea were therefore tested with regard to the presence of microbial contamination before and after brewing. In addition, pathogen growth in intentionally contaminated brewed tea was investigated over time. Teabags and brewed tea were highly contaminated (maximum mean values of 1.9 x 10(8) CFU/g raw tea), and it was found that the pathogen load of intentionally contaminated tea increased significantly (by a maximum of 10(5) colony-forming units/mL brewed tea) over time, suggesting a possible risk of patients developing a nosocomial infection when used in patient care.

Surveillance of antimicrobial use and antimicrobial resistance in intensive care units (SARI): 1. Antimicrobial use in German intensive care units.

OBJECTIVE: To study antimicrobial use for benchmarking and ensuring quality of antimicrobial treatment and to identify risk factors associated with the high use of antimicrobials in German intensive care units (ICUs) through implementation of the SARI (Surveillance of Antimicrobial Use and Antimicrobial Resistance in ICUs) system. DESIGN: Prospective, unit-based surveillance on antimicrobial use from February, 2000, until June, 2002. The data are standardised by use of the defined daily dose (DDD) for each antimicrobial defined by the WHO and by calculating use per 1000 patient days. SETTING: The data were obtained from 35 German ICUs and stratified by type of ICU (medical, surgical, interdisciplinary). RESULTS: To date, the project covers a total of 266,013 patient days in 744 reported ICU months and 354,356 DDDs. Mean antimicrobial use density (AD) was 1,332 DDD/1000 patient days and was correlated with length of stay. Penicillins with beta-lactamase inhibitor (AD 338.3) and quinolones (155.5) were the antimicrobial group with the highest ADs. Comparison with US ICARE (Intensive Care Antimicrobial Resistance Epidemiology)/AUR (Antimicrobial Use and Resistance) data revealed a higher AD for glycopeptides and 3rd generation cephalosporins in ICARE/AUR ICUs, but a higher AD for carbapenems in German SARI ICUs regardless of the type of ICU. In the multivariate analysis, length of stay was an independent risk factor for an AD above the 75% percentile of the total amount of antimicrobials used (OR 1.96 per day); likewise, for the AD above the 75% percentile of carbapenems (OR 1.90 per day) and penicillins with extended spectrum (OR 2.01 per day). High use of glycopeptides and quinolones (AD >75% percentile) correlated with central venous catheter (CVC) rate (OR 1.14 per CVC day per 100 patient days and 1.16, respectively). CONCLUSION: The SARI data on antimicrobials serve ICUs as a benchmark by which to improve the quality of antimicrobial drug administration and for international comparison.

Discrimination of Klebsiella pneumoniae and Klebsiella oxytoca phylogenetic groups and other Klebsiella species by use of amplified fragment length polymorphism.

Bacteria of the genus Klebsiella are opportunistic pathogens responsible for an increasing number of multiresistant infections in hospitals. The two clinically and epidemiologically most important species, Klebsiella pneumoniae and K. oxytoca, have recently been shown to be subdivided into three and two phylogenetic groups, respectively. The aim of this study was an in depth evaluation of the amplified fragment length polymorphism (AFLP) genetic characterization method for epidemiological and phylogenic analyzes of Klebsiella isolates. First, we investigated the variability of AFLP patterns for Klebsiella strains within and between different outbreaks. Second, by use of carefully characterized phylogenetically representative strains, we examined whether different Klebsiella species and phylogenetic groups can be discriminated using AFLP. Twenty-four strains originating from seven presumed outbreaks and 31 non-associated strains were investigated. The AFLP fingerprints of all epidemiologically associated strains showed three or fewer fragment differences, whereas unrelated strains differed by at least four fragments. Cluster analysis of the AFLP data revealed a very high concordance with the phylogenetic assignation of strains based on the gyrA sequence and ribotyping data. The species K. pneumoniae, K. oxytoca, K. terrigena and the possibly synonymous pair K. planticola/K. ornithinolytica each formed a separate cluster. Similarly, strains of the phylogenetic groups of K. pneumoniae and K. oxytoca fell into their corresponding clusters, with only two exceptions. This study provides a preliminary cut-off value for distinguishing epidemiologically non-related Klebsiella isolates based on AFLP data; it confirms the sharp delineation of the recently identified phylogenetic groups, and demonstrates that AFLP is suitable for identification of Klebsiella species and phylogenetic groups.

Flow cytometric measurements of neutrophil functions: the dependence on the stimulus to cell ratio.

Phagocytosis and antimicrobial killing of neutrophils has been quantitatively determined as a function of the stimulus (Candida albicans) to cell ratio R using two donor collectives containing a total of 115 blood samples. Analysis of the collectives in two different laboratories according to the same flow cytometric protocol for simultaneous measurement of neutrophil functions did not produce statistically significant differences. The number of phagocytosing leukocytes as well as that of killed fungi per leukocyte depends strongly on R. While each phagocytosing neutrophil kills one fungus at low values of R, each neutrophil kills on average 2.5 fungi for large R.

Development and mechanism of fluoroquinolone resistance in Legionella pneumophila.

The potential for selection in vitro of Legionella pneumophila mutants resistant to fluoroquinolones was investigated. Six distinct clinical isolates of L. pneumophila were subcultured in subinhibitory concentrations of ciprofloxacin, levofloxacin, clinafloxacin, trovafloxacin and moxifloxacin until MICs increased at least eight-fold. The numbers of serial passages required in microbroth dilution series were determined. The gyrA gene of the six parental strains, and 12 selected mutant strains, was sequenced. The five quinolones differed markedly in their ability to select mutants with decreased susceptibility. The average number of serial passages required was low in the cases of clinafloxacin (n = 10.6), ciprofloxacin and levofloxacin (both n = 13), but notably higher for trovafloxacin (n = 26.6) and moxifloxacin (n = 22.5). Five mutants treated with ciprofloxacin and three treated with moxifloxacin showed Thr83-->Lys or Thr83-->Ile amino acid changes in the gyrA gene. In conclusion, different quinolones lose their antimicrobial effect after a varying number of passages. This study demonstrated, for the first time to our knowledge, that gyrA in L. pneumophila is a possible target of fluoroquinolones.

Ceftriaxone versus other cephalosporins for perioperative antibiotic prophylaxis: a meta-analysis of 43 randomized controlled trials.

The efficacy of ceftriaxone versus other cephalosporins in the perioperative prophylaxis of surgical wound, urinary tract and respiratory tract infections was compared in a meta-analysis of randomized controlled trials published between 1986 and 1996, identified from the Medline, Embase, SIGLE, ROPU, DHSS-Data and Medikat Cologne databases. Studies were grouped by type of infection, operative specialty, wound classification, study quality and other factors, and assessed for relative risk (RR). Forty-three studies with a total of 13,482 patients met our inclusion criteria. RR for surgical wound infection (n = 13,303 patients) was 30% lower in the ceftriaxone versus control groups [98.3% confidence interval (CI): 0.55-0.89; p = 0.0002]. In urinary tract infections (n = 8,865 patients), the primary analysis of all studies showed marked superiority for ceftriaxone (RR: 0.53; 98.3% CI: 0.43-0.67) but not in studies with CDC-defined infections (RR: 0.63; 98.3% CI: 0.36-1.12). In both types of infection, ceftriaxone was superior in contaminated operations. The data showed no advantage for ceftriaxone in other operations. In respiratory tract infections (n = 9,567 patients), there was no significant difference: the RR was 0.81 (98.3% CI: 0.61-1.09; p = 0.04).

Detection of cross-transmission of multiresistant Gram-negative bacilli and Staphylococcus aureus in adult intensive care units by routine typing of clinical isolates.

OBJECTIVE: To determine the potential of laboratory services in identifying cross-transmission of multiresistant Gram-negative bacilli (MR GNB) and Staphylococcus aureus in adult intensive care units by routine typing of clinical isolates. METHODS: Over a 12-month period, isolates with indistinguishable PCR fingerprints were traced back to the source patients and their epidemiologic relationships were investigated. Possible episodes of cross-transmission were ascertained, and the validity of antibiograms in identifying the same cluster assessed. RESULTS: Of 3503 specimens received by the microbiological laboratory during 5372 patient days, 1295 cultures showed bacterial growth. Of these, 132 were primary isolates of MR GNB and 92 were primary isolates of S. aureus. Thirty-two MR GNB isolates (24%) shared fingerprints with one or more other isolates. Indistinguishable isolates from epidemiologically related patients suggested 17 episodes of cross-transmission. The positive and negative predictive values of antibiogram-based identification of these episodes were 19% and 72% respectively. S aureus displayed limited genetic diversity. The two most frequent genotypes contained 19 and 16 isolates, of which the majority appeared to be epidemiologically unrelated. CONCLUSIONS: Endemic transmission of MR GNB occurs mainly between two patients and remains unrecognized by conventional laboratory investigation. Rapid genetic typing methods identify patients involved in cross-transmission and give an insight into the population dynamics of MR GNB on adult intensive care units.