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1.  Mortality and molecular epidemiology associated with extended-spectrum β-lactamase production in Escherichia coli from bloodstream infection 
The rate of infections due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is growing worldwide. These infections are suspected to be related to increased mortality. We aimed to estimate the difference in mortality due to bloodstream infections (BSIs) with ESBL-positive and ESBL-negative E. coli isolates and to determine the molecular epidemiology of our ESBL-positive isolates.
Materials and methods
We performed a cohort study on consecutive patients with E. coli BSI between 2008 and 2010 at the Charité University Hospital. Collected data were ESBL production, basic demographic parameters, and underlying diseases by the Charlson comorbidity index (CCI). The presence of ESBL genes was analyzed by polymerase chain reaction (PCR) and sequencing. Phylogenetic groups of ESBL-positive E. coli were determined by PCR. Risk factors for mortality were analyzed by multivariable regression analysis.
We identified 115 patients with BSI due to E. coli with ESBL phenotype and 983 due to ESBL-negative E. coli. Fifty-eight percent (n=67) of the ESBL-positive BSIs were hospital-acquired. Among the 99 isolates that were available for PCR screening and sequencing, we found mainly 87 CTX-M producers, with CTX-M-15 (n=55) and CTX-M-1 (n=21) as the most common types. Parameters significantly associated with mortality were age, CCI, and length of stay before and after onset of BSI.
The most common ESBL genotypes in clinical isolates from E. coli BSIs were CTX-M-15 (58%) and CTX-M-1 (22%). ESBL production in clinical E. coli BSI isolates was not related to increased mortality. However, the common occurrence of hospital-acquired BSI due to ESBL-positive E. coli indicates future challenges for hospitals.
PMCID: PMC3958498  PMID: 24648746
BSI; mortality; ESBL-genotype; sepsis
2.  Serratia marcescens: an outbreak experience 
PMCID: PMC3944479  PMID: 24639671
Serratia marcescens; outbreak; neonates; infection control; multiresistance
3.  The Warmer the Weather, the More Gram-Negative Bacteria - Impact of Temperature on Clinical Isolates in Intensive Care Units 
PLoS ONE  2014;9(3):e91105.
We investigated the relationship between average monthly temperature and the most common clinical pathogens causing infections in intensive care patients.
A prospective unit-based study in 73 German intensive care units located in 41 different hospitals and 31 different cities with total 188,949 pathogen isolates (102,377 Gram-positives and 86,572 Gram-negatives) from 2001 to 2012. We estimated the relationship between the number of clinical pathogens per month and the average temperature in the month of isolation and in the month prior to isolation while adjusting for confounders and long-term trends using time series analysis. Adjusted incidence rate ratios for temperature parameters were estimated based on generalized estimating equation models which account for clustering effects.
The incidence density of Gram-negative pathogens was 15% (IRR 1.15, 95%CI 1.10–1.21) higher at temperatures ≥20°C than at temperatures below 5°C. E. cloacae occurred 43% (IRR = 1.43; 95%CI 1.31–1.56) more frequently at high temperatures, A. baumannii 37% (IRR = 1.37; 95%CI 1.11–1.69), S. maltophilia 32% (IRR = 1.32; 95%CI 1.12–1.57), K. pneumoniae 26% (IRR = 1.26; 95%CI 1.13–1.39), Citrobacter spp. 19% (IRR = 1.19; 95%CI 0.99–1.44) and coagulase-negative staphylococci 13% (IRR = 1.13; 95%CI 1.04–1.22). By contrast, S. pneumoniae 35% (IRR = 0.65; 95%CI 0.50–0.84) less frequently isolated at high temperatures. For each 5°C increase, we observed a 3% (IRR = 1.03; 95%CI 1.02–1.04) increase of Gram-negative pathogens. This increase was highest for A. baumannii with 8% (IRR = 1.08; 95%CI 1.05–1.12) followed by K. pneumoniae, Citrobacter spp. and E. cloacae with 7%.
Clinical pathogens vary by incidence density with temperature. Significant higher incidence densities of Gram-negative pathogens were observed during summer whereas S. pneumoniae peaked in winter. There is increasing evidence that different seasonality due to physiologic changes underlies host susceptibility to different bacterial pathogens. Even if the underlying mechanisms are not yet clear, the temperature-dependent seasonality of pathogens has implications for infection control and study design.
PMCID: PMC3944990  PMID: 24599500
4.  Risk Factors Associated with the Community-Acquired Colonization of Extended-Spectrum Beta-Lactamase (ESBL) Positive Escherichia Coli. An Exploratory Case-Control Study 
PLoS ONE  2013;8(9):e74323.
The number of extended-spectrum beta-lactamase (ESBL) positive (+) Escherichia coli is increasing worldwide. In contrast with many other multidrug-resistant bacteria, it is suspected that they predominantly spread within the community. The objective of this study was to assess factors associated with community-acquired colonization of ESBL (+) E. coli.
We performed a matched case-control study at the Charité University Hospital Berlin between May 2011 and January 2012. Cases were defined as patients colonized with community-acquired ESBL (+) E. coli identified <72 h after hospital admission. Controls were patients that carried no ESBL-positive bacteria but an ESBL-negative E.coli identified <72 h after hospital admission. Two controls per case were chosen from potential controls according to admission date. Case and control patients completed a questionnaire assessing nutritional habits, travel habits, household situation and language most commonly spoken at home (mother tongue). An additional rectal swab was obtained together with the questionnaire to verify colonization status. Genotypes of ESBL (+) E. coli strains were determined by PCR and sequencing. Risk factors associated with ESBL (+) E. coli colonization were analyzed by a multivariable conditional logistic regression analysis.
We analyzed 85 cases and 170 controls, respectively. In the multivariable analysis, speaking an Asian language most commonly at home (OR = 13.4, CI 95% 3.3–53.8; p<0.001) and frequently eating pork (≥3 meals per week) showed to be independently associated with ESBL colonization (OR = 3.5, CI 95% 1.8–6.6; p<0.001). The most common ESBL genotypes were CTX-M-1 with 44% (n = 37), CTX-M-15 with 28% (n = 24) and CTX-M-14 with 13% (n = 11).
An Asian mother tongue and frequently consuming certain types of meat like pork can be independently associated with the colonization of ESBL-positive bacteria. We found neither frequent consumption of poultry nor previous use of antibiotics to be associated with ESBL colonization.
PMCID: PMC3770595  PMID: 24040229
5.  Agreement among Healthcare Professionals in Ten European Countries in Diagnosing Case-Vignettes of Surgical-Site Infections 
PLoS ONE  2013;8(7):e68618.
Although surgical-site infection (SSI) rates are advocated as a major evaluation criterion, the reproducibility of SSI diagnosis is unknown. We assessed agreement in diagnosing SSI among specialists involved in SSI surveillance in Europe.
Twelve case-vignettes based on suspected SSI were submitted to 100 infection-control physicians (ICPs) and 86 surgeons in 10 European countries. Each participant scored eight randomly-assigned case-vignettes on a secure online relational database. The intra-class correlation coefficient (ICC) was used to assess agreement for SSI diagnosis on a 7-point Likert scale and the kappa coefficient to assess agreement for SSI depth on a three-point scale.
Intra-specialty agreement for SSI diagnosis ranged across countries and specialties from 0.00 (95%CI, 0.00–0.35) to 0.65 (0.45–0.82). Inter-specialty agreement varied from 0.04 (0.00–0.62) in to 0.55 (0.37–0.74) in Germany. For all countries pooled, intra-specialty agreement was poor for surgeons (0.24, 0.14–0.42) and good for ICPs (0.41, 0.28–0.61). Reading SSI definitions improved agreement among ICPs (0.57) but not surgeons (0.09). Intra-specialty agreement for SSI depth ranged across countries and specialties from 0.05 (0.00–0.10) to 0.50 (0.45–0.55) and was not improved by reading SSI definition.
Among ICPs and surgeons evaluating case-vignettes of suspected SSI, considerable disagreement occurred regarding the diagnosis, with variations across specialties and countries.
PMCID: PMC3706413  PMID: 23874690
6.  Attributable costs of ventilator-associated lower respiratory tract infection (LRTI) acquired on intensive care units: a retrospectively matched cohort study 
Lower respiratory tract infections (LRTI) are the most common hospital-acquired infections on ICUs. They have not only an impact on each patient’s individual health but also result in a considerable financial burden for the healthcare system. Our aim was to determine the costs and the length of stay of patients with ICU-acquired LRTI.
We used a retrospectively matched cohort design, comparing patients with ICU-acquired LRTI and ICU patients without LRTI. LRTI was diagnosed using the definitions of the Centers for Disease Control and Prevention (CDC). Study period was from January to December 2010 analyzing patients from 10 different ICUs (medical, surgical, interdisciplinary). The device utilization ratio was defined as number of ventilator days divided by number of patient days and the device-associated LRTI rate was defined as number of ventilator associated LRTI divided by number of ventilator days. Patients were matched by age, sex, and prospectively obtained Simplified Acute Physiology Score II (SAPS II). The length of ICU stay of control patients needed to be at least as long as that of LRTI-patients before onset of LRTI. We used the Wilcoxon signed-rank test for continuous variables and the McNemar’s test for categorical variables.
The analyzed ICUs had 40,772 patient days in the study period with a median ventilation utilization ratio of 56 (IQR 42–65). The median device-associated LRTI rate was 3.35 (IQR 0.96-5.36) per 1,000 ventilation days. We analyzed 49 patients with ICU-acquired LRTI and 49 respective controls without LRTI. The median hospital costs for LRTI patients were significantly higher than for patients without LRTI (45,041 € vs. 26,467 €; p < .001). The attributable costs per LRTI patient were 17,015 € (p < .001). Patients with ICU acquired LRTI stayed longer in the hospital than patients without (36 days vs. 24 days; p = 0.011). An LRTI lead to an attributable increase in length of stay by 9 days (p = 0.011).
ICU-acquired LRTI is associated with increased hospital costs and prolonged hospital stay. Hospital management should therefore implement control measurements to keep the incidence of ICU-acquired LRTI as low as possible.
PMCID: PMC3620937  PMID: 23556425
Lower respiratory tract infection; Intensive care unit; Costs and length of stay
7.  The impact of staffing on central venous catheter-associated bloodstream infections in preterm neonates – results of nation-wide cohort study in Germany 
Very low birthweight (VLBW) newborns on neonatal intensive care units (NICU) are at increased risk for developing central venous catheter-associated bloodstream infections (CVC BSI). In addition to the established intrinsic risk factors of VLBW newborns, it is still not clear which process and structure parameters within NICUs influence the prevalence of CVC BSI.
The study population consisted of VLBW newborns from NICUs that participated in the German nosocomial infection surveillance system for preterm infants (NEO-KISS) from January 2008 to June 2009. Structure and process parameters of NICUs were obtained by a questionnaire-based enquiry. Patient based date and the occurrence of BSI derived from the NEO-KISS database. The association between the requested parameters and the occurrance of CVC BSI and laboratory-confirmed BSI was analyzed by generalized estimating equations.
We analyzed data on 5,586 VLBW infants from 108 NICUs and found 954 BSI cases in 847 infants. Of all BSI cases, 414 (43%) were CVC-associated. The pooled incidence density of CVC BSI was 8.3 per 1,000 CVC days. The pooled CVC utilization ratio was 24.3 CVC-days per 100 patient days. A low realized staffing rate lead to an increased risk of CVC BSI (OR 1.47; p=0.008) and also of laboratory-confirmed CVC BSI (OR 1.78; p=0.028).
Our findings show that low levels of realized staffing are associated with increased rates of CVC BSI on NICUs. Further studies are necessary to determine a threshold that should not be undercut.
PMCID: PMC3643825  PMID: 23557510
Staffing; CVC; BSI; NICU; VLBW
8.  Health care workers causing large nosocomial outbreaks: a systematic review 
Staff in the hospital itself may be the source of a nosocomial outbreak (NO). But the role of undetected carriers as an outbreak source is yet unknown.
A systematic review was conducted to evaluate outbreaks caused by health care workers (HCW). The Worldwide Outbreak Database and PubMed served as primary sources of data. Articles in English, German or French were included. Other reviews were excluded. There were no restrictions with respect to the date of publication.
Data on setting, pathogens, route of transmission, and characteristics of the HCW was retrieved. Data from large outbreaks were compared to smaller outbreaks.
152 outbreaks were included, mainly from surgery, neonatology, and gynecology departments. Most frequent corresponding infections were surgical site infections, infection by hepatitis B virus, and septicemia. Hepatitis B virus (27 NO), S. aureus (49 NO) and S. pyogenes (19 NO) were the predominant pathogens involved. 59 outbreaks (41.5%) derived from physicians and 56 outbreaks (39.4%) derived from nurses. Transmission mainly occurred via direct contact. Surgical and pediatric departments were significantly associated with smaller outbreaks, and gynecology with larger outbreaks. Awareness of carrier status significantly decreased the risk of causing large outbreaks.
As NO caused by HCW represent a rare event, screening of personnel should not be performed regularly. However, if certain species of microorganisms are involved, the possibility of a carrier should be taken into account.
PMCID: PMC3599984  PMID: 23432927
Nosocomial outbreak; Staff; Personnel; Health care workers; Health care associated infection
10.  MRSA Transmission on a Neonatal Intensive Care Unit: Epidemiological and Genome-Based Phylogenetic Analyses 
PLoS ONE  2013;8(1):e54898.
Methicillin-resistant Staphylococcus aureus (MRSA) may cause prolonged outbreaks of infections in neonatal intensive care units (NICUs). While the specific factors favouring MRSA spread on neonatal wards are not well understood, colonized infants, their relatives, or health-care workers may all be sources for MRSA transmission. Whole-genome sequencing may provide a new tool for elucidating transmission pathways of MRSA at a local scale.
Methods and Findings
We applied whole-genome sequencing to trace MRSA spread in a NICU and performed a case-control study to identify risk factors for MRSA transmission. MRSA genomes had accumulated sequence variation sufficiently fast to reflect epidemiological linkage among individual patients, between infants and their mothers, and between infants and staff members, such that the relevance of individual nurses’ nasal MRSA colonization for prolonged transmission could be evaluated. In addition to confirming previously reported risk factors, we identified an increased risk of transmission from infants with as yet unknown MRSA colonisation, in contrast to known MRSA-positive infants.
The integration of epidemiological (temporal, spatial) and genomic data enabled the phylogenetic testing of several hypotheses on specific MRSA transmission routes within a neonatal intensive-care unit. The pronounced risk of transmission emanating from undetected MRSA carriers suggested that increasing the frequency or speed of microbiological diagnostics could help to reduce transmission of MRSA.
PMCID: PMC3561456  PMID: 23382995
11.  Concordance between European and US case definitions of healthcare-associated infections 
Surveillance of healthcare-associated infections (HAI) is a valuable measure to decrease infection rates. Across Europe, inter-country comparisons of HAI rates seem limited because some countries use US definitions from the US Centers for Disease Control and Prevention (CDC/NHSN) while other countries use European definitions from the Hospitals in Europe Link for Infection Control through Surveillance (HELICS/IPSE) project. In this study, we analyzed the concordance between US and European definitions of HAI.
An international working group of experts from seven European countries was set up to identify differences between US and European definitions and then conduct surveillance using both sets of definitions during a three-month period (March 1st -May 31st, 2010). Concordance between case definitions was estimated with Cohen’s kappa statistic (κ).
Differences in HAI definitions were found for bloodstream infection (BSI), pneumonia (PN), urinary tract infection (UTI) and the two key terms “intensive care unit (ICU)-acquired infection” and “mechanical ventilation”. Concordance was analyzed for these definitions and key terms with the exception of UTI. Surveillance was performed in 47 ICUs and 6,506 patients were assessed. One hundred and eighty PN and 123 BSI cases were identified. When all PN cases were considered, concordance for PN was κ = 0.99 [CI 95%: 0.98-1.00]. When PN cases were divided into subgroups, concordance was κ = 0.90 (CI 95%: 0.86-0.94) for clinically defined PN and κ = 0.72 (CI 95%: 0.63-0.82) for microbiologically defined PN. Concordance for BSI was κ = 0.73 [CI 95%: 0.66-0.80]. However, BSI cases secondary to another infection site (42% of all BSI cases) are excluded when using US definitions and concordance for BSI was κ = 1.00 when only primary BSI cases, i.e. Europe-defined BSI with ”catheter” or “unknown” origin and US-defined laboratory-confirmed BSI (LCBI), were considered.
Our study showed an excellent concordance between US and European definitions of PN and primary BSI. PN and primary BSI rates of countries using either US or European definitions can be compared if the points highlighted in this study are taken into account.
PMCID: PMC3527198  PMID: 22958646
Bloodstream infection; Pneumonia; Definitions; Healthcare-associated infections
12.  The step from a voluntary to a mandatory national nosocomial infection surveillance system: the influence on infection rates and surveillance effect 
The German national nosocomial infection surveillance system, KISS, has a component for very low birth weight (VLBW) infants (called NEO-KISS) which changed from a system with voluntary participation and confidential data feedback to a system with mandatory participation and confidential feedback.
In order to compare voluntary and mandatory surveillance data, two groups were defined by the surveillance start date. Neonatal intensive care unit (NICU) parameters and infection rates of the NICUs in both groups were compared. In order to analyze the surveillance effect on primary bloodstream infection rates (BSI), all VLBW infants within the first three years of participation in both groups were considered. The adjusted effect measures for the year of participation were calculated.
An increase from 49 NICUs participating in 2005 to 152 in 2006 was observed after the introduction of mandatory participation. A total of 4280 VLBW infants was included in this analysis. Healthcare-associated incidence densities rates were similar in both groups. Using multivariate analysis with the endpoint primary BSI rate and comparing the first and third year of participation lead to an adjusted incidence rate ratio (IRR) of 0.78 (CI95 0.66-0.93) for old (voluntary) and 0.81 (CI95 0.68-0.97) for new (mandatory) participants.
The step from a voluntary to a mandatory HCAI surveillance system alone may lead to substantial improvements on a countrywide scale.
PMCID: PMC3489557  PMID: 22958509
Surveillance; Nosocomial infections; Neonatal intensive care unit; Bloodstream infection
13.  Individual units rather than entire hospital as the basis for improvement: the example of two Methicillin resistant Staphylococcus aureus cohort studies 
Two MRSA surveillance components exist within the German national nosocomial infection surveillance system KISS: one for the whole hospital (i.e. only hospital based data and no rates for individual units) and one for ICU-based data (rates for each individual ICU). The objective of this study was to analyze which surveillance system (a hospital based or a unit based) leads to a greater decrease in incidence density of nosocomial MRSA
Two cohort studies of surveillance data were used: Data from a total of 224 hospitals and 359 ICUs in the period from 2004 to 2009. Development over time was described first for both surveillance systems. In a second step only data were analyzed from those hospitals/ICUs with continuous participation for at least four years. Incidence rate ratios (IRR) with 95% confidence intervals were calculated to compare incidence densities between different time intervals.
In the baseline year the mean MRSA incidence density of hospital acquired MRSA cases was 0.25 and the mean incidence density of ICU-acquired MRSA was 1.25 per 1000 patient days. No decrease in hospital-acquired MRSA rates was found in a total of 111 hospitals with continuous participation in the hospital- based system. However, in 159 ICUs with continuous participation in the unit-based system, a significant decrease of 29% in ICU-acquired MRSA was identified.
A unit-based approach of surveillance and feedback seems to be more successful in decreasing nosocomial MRSA rates, compared to a hospital-based approach. Therefore each surveillance system should provide unit-based data to stimulate activities on the unit level.
PMCID: PMC3436609  PMID: 22958320
Infection prevention; Surveillance; MRSA; Quality management
14.  Decreasing healthcare-associated infections (HAI) is an efficient method to decrease healthcare-associated Methicillin-resistant S.aureus (MRSA) infections Antimicrobial resistance data from the German national nosocomial surveillance system KISS 
By analysing the data of the intensive care unit (ICU) component of the German national nosocomial infection surveillance system (KISS) during the last ten years, we have observed a steady increase in the MRSA rates (proportions) from 2001 to 2005 and only a slight decrease from 2006 to 2010. The objective of this study was to investigate the development of the incidence density of nosocomial MRSA infections because this is the crucial outcome for patients.
Data from 103 ICUs with ongoing participation during the observation period were included. The pooled incidence density of nosocomial MRSA infections decreased significantly from 0.37 per 1000 patient days in 2001 to 0.15 per 1000 patient days in 2010 (RR = 0.40; CI95 0.29-0.55). This decrease was proportional to the significant decrease of all HCAI during the same time period (RR = 0.61; CI95 0.58-0.65).
The results underline the need to concentrate infection control activities on measures to control HCAI in general rather than focusing too much on specific MRSA prevention measures. MRSA rates (proportions) are not a very useful indicator of the situation.
PMCID: PMC3415117  PMID: 22958746
Surveillance; MRSA; epidemiology; Staphylococcus aureus
15.  Screening and control of methicillin-resistant Staphylococcus aureus in 186 intensive care units: different situations and individual solutions 
Critical Care  2011;15(6):R285.
Controversy exists about the benefit of screening for prevention of methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs) and recent studies have shown conflicting results. The aim of this observational study was to describe and evaluate the association between MRSA incidence densities (IDs) and screening and control measures in ICUs participating in the German Nosocomial Infection Surveillance System.
The surveillance module for multidrug-resistant bacteria collects data on MRSA cases in ICUs with the aim to provide a national reference and a tool for evaluation of infection control management. The median IDs of MRSA cases per 1000 patient-days (pd) with the interquartile range (IQR) were calculated from the pooled data of 186 ICUs and correlated with parameters derived from a detailed questionnaire regarding ICU structure, microbiological diagnostics and MRSA screening and control measures. The association between questionnaire results and MRSA cases was evaluated by generalized linear regression models.
One hundred eighty-six ICUs submitted data on MRSA cases for 2007 and 2008 and completed the questionnaire. During the period of analysis, 4935 MRSA cases occurred in these ICUs; of these, 3928 (79.6%) were imported and 1007 MRSA cases (20.4%) were ICU-acquired. Median MRSA IDs were 3.23 (IQR 1.24-5.73), 2.24 (IQR 0.63-4.30) and 0.64 (IQR 0.17-1.39) per 1000 pd for all cases, imported and ICU-acquired MRSA cases, respectively. MRSA IDs as well as implemented MRSA screening and control measures varied widely between ICUs. ICUs performing universal admission screening had significantly higher MRSA IDs than ICUs performing targeted or no screening. Separate regression models for ICUs with different screening strategies included the incidence of imported MRSA cases, the type of ICU, and the length of stay in independent association with the number of ICU-acquired MRSA cases.
The analysis shows that MRSA IDs and structural parameters differ considerably between ICUs. In response, ICUs have combined screening and control measures in many ways to achieve various individual solutions. The incidence of imported MRSA cases might be helpful for consideration in the planning of MRSA control programmes.
PMCID: PMC3388634  PMID: 22118016
16.  Five-years surveillance of invasive aspergillosis in a university hospital 
BMC Infectious Diseases  2011;11:163.
As the most common invasive fungal infection, invasive aspergillosis (IA) remains a serious complication in immunocompromised patients, leading to increased mortality. Antifungal therapy is expensive and may result in severe adverse effects.
The aim of this study was to determine the incidence of invasive aspergillosis (IA) cases in a tertiary care university hospital using a standardized surveillance method.
All inpatients at our facility were screened for presence of the following parameters: positive microbiological culture, pathologist's diagnosis and antifungal treatment as reported by the hospital pharmacy. Patients fulfilling one or more of these indicators were further reviewed and, if appropriate, classified according to international consensus criteria (EORTC).
704 patients were positive for at least one of the indicators mentioned above. Applying the EORTC criteria, 214 IA cases were detected, of which 56 were proven, 25 probable and 133 possible. 44 of the 81 (54%) proven and probable cases were considered health-care associated. 37 of the proven/probable IA cases had received solid organ transplantation, an additional 8 had undergone stem cell transplantation, and 10 patients were suffering from some type of malignancy. All the other patients in this group were also suffering from severe organic diseases, required long treatment and experienced several clinical complications. 7 of the 56 proven cases would have been missed without autopsy. After the antimycotic prophylaxis regimen was altered, we noticed a significant decrease (p = 0.0004) of IA during the investigation period (2003-2007).
Solid organ and stem cell transplantation remain important risk factors for IA, but several other types of immunosuppression should also be kept in mind. Clinical diagnosis of IA may be difficult (in this study 13% of all proven cases were diagnosed by autopsy only). Thus, we confirm the importance of IA surveillance in all high-risk patients.
PMCID: PMC3128051  PMID: 21651773
surveillance; invasive Aspergillosis; epidemiology; pathology
17.  An evidence-based recommendation on bed head elevation for mechanically ventilated patients 
Critical Care  2011;15(2):R111.
A semi-upright position in ventilated patients is recommended to prevent ventilator-associated pneumonia (VAP) and is one of the components in the Ventilator Bundle of the Institute for Health Care Improvement. This recommendation, however, is not an evidence-based one.
A systematic review on the benefits and disadvantages of semi-upright position in ventilated patients was done according to PRISMA guidelines. Then a European expert panel developed a recommendation based on the results of the systematic review and considerations beyond the scientific evidence in a three-round electronic Delphi procedure.
Three trials (337 patients) were included in the review. The results showed that it was uncertain whether a 45° bed head elevation was effective or harmful with regard to the occurrence of clinically suspected VAP, microbiologically confirmed VAP, decubitus and mortality, and that it was unknown whether 45° elevation for 24 hours a day increased the risk for thromboembolism or hemodynamic instability. A group of 22 experts recommended elevating the head of the bed of mechanically ventilated patients to a 20 to 45° position and preferably to a ≥30° position as long as it does not pose risks or conflicts with other nursing tasks, medical interventions or patients' wishes.
Although the review failed to prove clinical benefits of bed head elevation, experts prefer this position in ventilated patients. They made clear that the position of a ventilated patient in bed depended on many determinants. Therefore, given the scientific uncertainty about the benefits and harms of a semi-upright position, this position could only be recommended as the preferred position with the necessary restrictions.
PMCID: PMC3219392  PMID: 21481251
18.  Nosocomial methicillin resistant Staphylococcus aureus pneumonia - epidemiology and trends based on data of a network of 586 German ICUs (2005-2009) 
The epidemiology of MRSA pneumonia varies across countries. One of the most import risk factors for the development of nosocomial MRSA pneumonia is mechanical ventilation. Methicillin resistance in S. aureus ventilator associated pneumonia (VAP) ranged between 37% in German, 54% in the US American and 78% in Asian and Latin American ICUs. In 2009, the incidence density of nosocomial VAP caused by MRSA was 0.28 per 1000 ventilation days in a network of 586 German ICUs. Incidences peaked in neurological and neurosurgical ICUs. Crude hospital mortality in studies performed after 2005 lay between 27% and 59% and attributable MRSA pneumonia mortality at 40%. Since 2005, US American and German data indicate decreasing trends for MRSA pneumonia. Measures to reduce MRSA pneumonia or to control the spread of MRSA include hand hygiene, standard and contact precautions, oral contamination with chlor hexidine, skin decontamination with antiseptics, screening, and (possibly) patient isolation in a single room.
PMCID: PMC3352100  PMID: 21163726
methicillin resistant Staphylococcus aureus; pneumonia; nosocomial; mortality; risk factor; age; change over time
19.  Dramatic increase of third-generation cephalosporin-resistant E. coli in German intensive care units: secular trends in antibiotic drug use and bacterial resistance, 2001 to 2008 
Critical Care  2010;14(3):R113.
The objective of the present study was to analyse secular trends in antibiotic consumption and resistance data from a network of 53 intensive care units (ICUs).
The study involved prospective unit and laboratory-based surveillance in 53 German ICUs from 2001 through 2008. Data were calculated on the basis of proportions of nonduplicate resistant isolates, resistance densities (that is, the number of resistant isolates of a species per 1,000 patient-days) and an antimicrobial usage density (AD) expressed as daily defined doses (DDD) and normalised per 1,000 patient-days.
Total mean antibiotic use remained stable over time and amounted to 1,172 DDD/1,000 patient-days (range 531 to 2,471). Carbapenem use almost doubled to an AD of 151 in 2008. Significant increases were also calculated for quinolone (AD of 163 in 2008) and third-generation and fourth-generation cephalosporin use (AD of 117 in 2008). Aminoglycoside consumption decreased substantially (AD of 86 in 2001 and 24 in 2008). Resistance proportions were as follows in 2001 and 2008, respectively: methicillin-resistant Staphylococcus aureus (MRSA) 26% and 20% (P = 0.006; trend test showed a significant decrease), vancomycin-resistant enterococcus (VRE) faecium 2.3% and 8.2% (P = 0.008), third-generation cephalosporin (3GC)-resistant Escherichia. coli 1.2% and 19.7% (P < 0.001), 3GC-resistant Klebsiella pneumoniae 3.8% and 25.5% (P < 0.001), imipenem-resistant Acinetobacter baumannii 1.1% and 4.5% (P = 0.002), and imipenem-resistant K. pneumoniae 0.4% and 1.1%. The resistance densities did not change for MRSA but increased significantly for VRE faecium and 3GC-resistant E. coli and K. pneumoniae. In 2008, the resistance density for MRSA was 3.73, 0.48 for VRE, 1.39 for 3GC-resistant E. coli and 0.82 for K. pneumoniae.
Although total antibiotic use did not change over time in German ICUs, carbapenem use doubled. This is probably due to the rise in 3GC-resistant E. coli and K. pneumoniae. Increased carbapenem consumption was associated with carbapenem-resistant K. pneumoniae carbapenemase-producing bacteria and imipenem-resistant A. baumannii.
PMCID: PMC2911759  PMID: 20546564
20.  The microbiological quality of air improves when using air conditioning systems in cars 
BMC Infectious Diseases  2010;10:146.
Because of better comfort, air conditioning systems are a common feature in automobiles these days. However, its impact on the number of particles and microorganisms inside the vehicle - and by this its impact on the risk of an allergic reaction - is yet unknown.
Over a time period of 30 months, the quality of air was investigated in three different types of cars (VW Passat, VW Polo FSI, Seat Alhambra) that were all equipped with a automatic air conditioning system. Operation modes using fresh air from outside the car as well as circulating air from inside the car were examined. The total number of microorganisms and the number of mold spores were measured by impaction in a high flow air sampler. Particles of 0.5 to 5.0 μm diameter were counted by a laser particle counter device.
Overall 32 occasions of sampling were performed. The concentration of microorganisms outside the cars was always higher than it was inside the cars. Few minutes after starting the air conditioning system the total number of microorganisms was reduced by 81.7%, the number of mold spores was reduced by 83.3%, and the number of particles was reduced by 87.8%. There were no significant differences neither between the types of cars nor between the types of operation mode of the air conditioning system (fresh air vs. circulating air). All parameters that were looked for in this study improved during utilization of the car's air conditioning system.
We believe that the risk of an allergic reaction will be reduced during use also. Nevertheless, we recommend regular maintenance of the system and replacement of older filters after defined changing intervals.
PMCID: PMC2890006  PMID: 20515449
21.  Early- and Late-Onset Pneumonia: Is This Still a Useful Classification?▿  
The choice of empirical treatment of nosocomial pneumonia in the intensive-care unit (ICU) used to rely on the interval after the start of mechanical ventilation. Nowadays, however, the question of whether in fact there is a difference in the distribution of causative pathogens is under debate. Data from 308 ICUs from the German National Nosocomial Infection Surveillance System, including information on relevant pathogens isolated in 11,285 cases of nosocomial pneumonia from 1997 to 2004, were used for our evaluation. Each individual pneumonia case was allocated either to early- or to late-onset pneumonia, with three differentiation criteria: onset on the 4th day, the 5th day, or the 7th day in the ICU. The frequency of pathogens was evaluated according to these categories. A total of 5,066 additional cases of pneumonia were reported from 2005 to 2006, after the CDC criteria had been modified. From 1997 to 2004, the most frequent microorganisms were Staphylococcus aureus (2,718 cases, including 720 with methicillin [meticillin]-resistant S. aureus), followed by Pseudomonas aeruginosa (1,837 cases), Klebsiella pneumoniae (1,305 cases), Escherichia coli (1,137 cases), Enterobacter spp. (937 cases), streptococci (671 cases), Haemophilus influenzae (509 cases), Acinetobacter spp. (493 cases), and Stenotrophomonas maltophilia (308 cases). The order of the four most frequent pathogens (accounting for 53.7% of all pathogens) was the same in both groups and was independent of the cutoff categories applied: S. aureus was first, followed by P. aeruginosa, K. pneumoniae, and E. coli. Thus, the predictabilities of the occurrence of pathogens were similar for the earlier (1997-to-2004) and later (2005-to-2006) time frames. This classification is no longer helpful for empirical antibiotic therapy, since the pathogens are the same for both groups.
PMCID: PMC2704703  PMID: 19364852
23.  Impact of a silver layer on the membrane of tap water filters on the microbiological quality of filtered water 
Bacteria in the hospital's drinking water system represent a risk for the acquisition of a nosocomial infection in the severely immunocompromised host. Terminal tap water filters may be used to prevent nosocomial Legionnaires' disease. We present data from water samples using an improved kind of tap water filters.
In a blinded study on an intermediate care unit of the thoracic surgery department, a modified type of the Germlyser water filter (Aqua-Free Membrane Technology) with a newly-introduced silver layer on the filtration membrane was compared to its preceding type without such a layer on 15 water outlets. We determined growth of Legionella, other pathogenic bacteria, and the total heterotrophic plate count in unfiltered water and filtered water samples after filter usage intervals of 1 through 4 weeks.
A total of 299 water samples were tested. Twenty-nine of the 60 unfiltered water samples contained Legionella of various serogroups (baseline value). In contrast, all samples filtered by the original water filter and all but one of the water samples filtered by the modified filter type remained Legionella-free. No other pathogenic bacteria were detected in any filtered sample. The total plate count in water samples increased during use of both kinds of filters over time. However, for the first 7 days of use, there were significantly fewer water samples containing >100 CFU per mL when using the new filter device compared with the older filters or taps with no filter. No advantage was seen thereafter.
The use of this type of terminal water filter is an appropriate method to protect immunocompromised patients from water-borne pathogens such as Legionella.
PMCID: PMC2569947  PMID: 18842119
25.  Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models 
Critical Care  2008;12(2):R44.
Pneumonia is a very common nosocomial infection in intensive care units (ICUs). Many studies have investigated risk factors for the development of infection and its consequences. However, the evaluation in most of theses studies disregards the fact that there are additional competing events, such as discharge or death.
A prospective cohort study was conducted over 18 months in five intensive care units at one university hospital. All patients that were admitted for at least 2 days were included, and surveillance of nosocomial pneumonia was conducted. Various potential risk factors (baseline- and time-dependent) were evaluated in two competing risks models: the acquisition of nosocomial pneumonia and discharge (dead or alive; model 1) and for the risk of death in the ICU and discharge alive (model 2).
Patients from 1,876 admissions were included. A total of 158 patients developed nosocomial pneumonia. The main risk factors for nosocomial pneumonia in the multivariate analysis in model 1 were: elective surgery (cause-specific hazard ratio = 1.95; 95% CI 1.33 to 2.85) or emergency surgery (1.59; 95% CI 1.10 to 2.28) prior to ICU admission, usage of a nasogastric tube (3.04; 95% CI 1.25 to 7.37) and mechanical ventilation (5.90; 95% CI 2.47 to 14.09). Nosocomial pneumonia prolonged the length of ICU stay but was not directly associated with a fatal outcome (p = 0.55).
More studies using competing risk models, which provide more accurate data compared to naive survival curves or logistic models, should be carried out to verify the impact of risk factors and patient characteristics for the acquisition of nosocomial infections and infection-associated mortality.
PMCID: PMC2447589  PMID: 18384672

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