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1.  Health-care associated infections rates, length of stay, and bacterial resistance in an intensive care unit of Morocco: Findings of the International Nosocomial Infection Control Consortium (INICC) 
Most studies related to healthcare-associated infection (HAI) were conducted in the developed countries. We sought to determine healthcare-associated infection rates, microbiological profile, bacterial resistance, length of stay (LOS), and extra mortality in one ICU of a hospital member of the International Infection Control Consortium (INICC) in Morocco.
We conducted prospective surveillance from 11/2004 to 4/2008 of HAI and determined monthly rates of central vascular catheter-associated bloodstream infection (CVC-BSI), catheter-associated urinary tract infection (CAUTI) and ventilator-associated pneumonia (VAP). CDC-NNIS definitions were applied. device-utilization rates were calculated by dividing the total number of device-days by the total number of patient-days. Rates of VAP, CVC-BSI, and CAUTI per 1000 Device-days were calculated by dividing the total number of HAI by the total number of specific Device-days and multiplying the result by 1000.
1,731 patients hospitalized for 11,297 days acquired 251 HAIs, an overall rate of 14.5%, and 22.22 HAIs per 1,000 ICU-days. The central venous catheter-related bloodstream infections (CVC-BSI) rate found was 15.7 per 1000 catheter-days; the ventilator-associated pneumonia (VAP) rate found was 43.2 per 1,000 ventilator-days; and the catheter-associated urinary tract infections (CAUTI) rate found was 11.7 per 1,000 catheter-days.
Overall 25.5% of all Staphylococcus aureus HAIs were caused by methicillin-resistant strains, 78.3% of Coagulase-negative-staphylococci were methicillin resistant as well. 75.0% of Klebsiella were resistant to ceftriaxone and 69.5% to ceftazidime. 31.9% of E. Coli were resistant to ceftriaxone and 21.7% to ceftazidime. 68.4% of Enterobacter sp were resistant to ceftriaxone, 55.6% to ceftazidime, and 10% to imipenem; 35.6% of Pseudomonas sp were resistant to ceftazidime and 13.5% to imipenem.
LOS of patients was 5.1 days for those without HAI, 9.0 days for those with CVC-BSI, 10.6 days for those with VAP, and 13.7 days for those with CAUTI.
Extra mortality was 56.7% (RR, 3.28; P =< 0.001) for VAP, 75.1% (RR, 4.02; P = 0.0027) for CVC-BSI, and 18.7% (RR, 1.75; P = 0.0218) for CAUTI.
HAI rates, LOS, mortality, and bacterial resistance were high. Even if data may not reflect accurately the clinical setting of the country, programs including surveillance, infection control, and antibiotic policy are a priority in Morocco.
PMCID: PMC2765432  PMID: 19811636
2.  International Nosocomial Infection Control Consortium Findings of Device-Associated Infections Rate in an Intensive Care Unit of a Lebanese University Hospital 
To determine the rates of device-associated healthcare-associated infections (DA-HAI), microbiological profile, bacterial resistance, length of stay (LOS), excess mortality and hand hygiene compliance in one intensive care unit (ICU) of a hospital member of the International Infection Control Consortium (INICC) in Beirut, Lebanon.
Materials and Methods:
An open label, prospective cohort, active DA-HAI surveillance study was conducted on adults admitted to a tertiary-care ICU in Lebanon from November 2007 to March 2010. The protocol and methodology implemented were developed by INICC. Data collection was performed in the participating ICUs. Data uploading and analyses were conducted at INICC headquarters on proprietary software. DA-HAI rates were recorded by applying the definitions of the National Healthcare Safety Network (NHSN) at the US Centers for Disease Control and Prevention (CDC). We analyzed the DA-HAI, mechanical ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLA-BSI), and catheter-associated urinary tract infection (CAUTI) rates, microorganism profile, excess LOS, excess mortality, and hand hygiene compliance.
A total of 666 patients hospitalized for 5,506 days acquired 65 DA-HAIs, an overall rate of 9.8% [(95% confidence interval (CI) 7.6–12.3], and 11.8 (95% CI 9.1–15.0) DA-HAIs per 1000 ICU-days. The CLA-BSI rate was 5.2 (95% CI 2.8–8.7) per 1000 catheter-days; the VAP rate was 8.1 (95% CI 5.5–11.7) per 1000 ventilator-days; and the CAUTI rate was 4.1 (95% CI 2.6–6.2) per 1000 catheter-days. LOS of patients was 7.3 days for those without DA-HAI, 13.8 days for those with CLA-BSI, 18.8 days for those with VAP. Excess mortality was 40.9% [relative risk (RR) 3.14; P 0.004] for CLA-BSI. Mortality of VAP and CAUTI was not significantly different from patients without DA-HAI. Escherichia coli was the most common isolated microorganism. Overall hand hygiene compliance was 84.9% (95% CI 82.3–87.3).
DA-HAI rates, bacterial resistance, LOS and mortality were moderately high, below INICC overall data and above CDC-NHSN data. Infection control programs including surveillance and antibiotic policies are essential and continue to be a priority in Lebanon.
PMCID: PMC3326952  PMID: 22529622
Catheter associated urinary tract infection; Central line associated bloodstream infection; Ventilator associated pneumonia; Intensive care unit; Lebanon; International Nosocomial Infection Control Consortium
3.  International Nosocomial Infection Control Consortium (INICC) national report on device-associated infection rates in 19 cities of Turkey, data summary for 2003–2012 
Device-associated healthcare-acquired infections (DA-HAI) pose a threat to patient safety, particularly in the intensive care unit (ICU). We report the results of the International Infection Control Consortium (INICC) study conducted in Turkey from August 2003 through October 2012.
A DA-HAI surveillance study in 63 adult, paediatric ICUs and neonatal ICUs (NICUs) from 29 hospitals, in 19 cities using the methods and definitions of the U.S. NHSN and INICC methods.
We collected prospective data from 94,498 ICU patients for 647,316 bed days. Pooled DA-HAI rates for adult and paediatric ICUs were 11.1 central line-associated bloodstream infections (CLABSIs) per 1000 central line (CL)-days, 21.4 ventilator-associated pneumonias (VAPs) per 1000 mechanical ventilator (MV)-days and 7.5 catheter-associated urinary tract infections (CAUTIs) per 1000 urinary catheter-days. Pooled DA-HAI rates for NICUs were 30 CLABSIs per 1000 CL-days, and 15.8 VAPs per 1000 MV-days. Extra length of stay (LOS) in adult and paediatric ICUs was 19.4 for CLABSI, 8.7 for VAP and 10.1 for CAUTI. Extra LOS in NICUs was 13.1 for patients with CLABSI and 16.2 for patients with VAP. Extra crude mortality was 12% for CLABSI, 19.4% for VAP and 10.5% for CAUTI in ICUs, and 15.4% for CLABSI and 10.5% for VAP in NICUs. Pooled device use (DU) ratios for adult and paediatric ICUs were 0.54 for MV, 0.65 for CL and 0.88 for UC, and 0.12 for MV, and 0.09 for CL in NICUs. The CLABSI rate was 8.5 per 1,000 CL days in the Medical Surgical ICUs included in this study, which is higher than the INICC report rate of 4.9, and more than eight times higher than the NHSN rate of 0.9. Similarly, the VAP and CAUTI rates were higher compared with U.S. NHSN (22.3 vs. 1.1 for VAP; 7.9 vs. 1.2 for CAUTI) and with the INICC report (22.3 vs. 16.5 in VAP; 7.9 vs. 5.3 in CAUTI).
DA-HAI rates and DU ratios in our ICUs were higher than those reported in the INICC global report and in the US NHSN report.
PMCID: PMC4255447  PMID: 25403704
Hospital infection; Nosocomial infection; Healthcare-associated infection; INICC; International Nosocomial Infection Consortium; Turkey; Device-associated infection; Antibiotic resistance; Ventilator-associated pneumonia; Catheter-associated urinary tract infection; Central line-associated bloodstream infections; Bloodstream infection; Urinary tract infection; Network
4.  Microbiology, resistance patterns, and risk factors of mortality in ventilator-associated bacterial pneumonia in a Northern Thai tertiary-care university based general surgical intensive care unit 
Ventilator-associated pneumonia (VAP) occurrence, causative pathogens, and resistance patterns in surgical intensive care units (SICU) are different between Western and developing Asian countries. In Thailand, resistant organisms have progressively increased in the last decade. However, the evidence describing causes of VAP and its outcomes, especially secondary to resistant pathogens, in Asian developing countries’ SICUs is very limited. Therefore, the objective of this study was to describe the incidence, pathogen characteristics, and risk factors that impact mortality and patient survival following VAP in a tertiary Northern Thai SICU.
Between 2008 and 2012, VAP occurred in a total of 150 patients in Chiang Mai University’s general SICUs (6.3±2.8 cases per 1,000 mechanical ventilator days). The following clinical data were collected from 46 patients who died and 104 patients who survived: microbiologic results, susceptible patterns, and survival status at hospital discharge. Antimicrobial susceptibility patterns were classified as susceptible, multidrug resistant (MDR), extensively drug resistant (XDR), and pan-drug resistant (PDR). The hazard ratio (HR) was calculated for risk factor analysis.
Regarding the microbiology, gram negative organisms were the major pathogens (n=142, 94.7%). The first three most common organisms were Acinetobacter baumannii (38.7% of all organisms, mortality 41.4%), Klebsiella pneumoniae (17.3%, mortality 30.8%), and Pseudomonas aeruginosa (16.7%, mortality 16%) respectively. The most common gram positive organism was Staphylococcus aureus (4.0%, mortality 50%). The median day of VAP occurrence were significantly different between the three groups (P<0.01): susceptible (day 4), MDR (day 5), and XDR (day 6.5). Only half of all VAP cases were caused by susceptible organisms. Antibiotic resistance was demonstrated by 49.3% of the gram negative organisms and 62.5% of the gram positive organisms. Extensive drug resistance was evident only in Acinetobacter baumannii (30.6%) and Pseudomonas aeruginosa (1.3%). No pan-drug resistance was found during surveillance. The significant HR risk factors were age (P=0.03), resistant organisms (P=0.04), XDR (P=0.02), and acute physiology and chronic health evaluation II score (<0.01). Acinetobacter baumannii (P=0.06) and intubation due to severe sepsis (P=0.08) demonstrated a trend toward a significant increase in the HR. On the other hand, there were significantly decreased HRs in trauma patients (P=0.01). Initial administration of appropriate antibiotic therapy had a tendency toward a significant decrease in the HR (P=0.08).
Gram negative organisms were the primary cause of bacterial VAP in Chiang Mai University’s general SICU. Resistant strains were present in half of all VAP cases and were associated with the day of VAP onset. Regarding risk factors, age, acute physiology, chronic health evaluation II score, resistant organisms (especially XDR), and being a non-trauma patient increased the risk of mortality.
PMCID: PMC4140702  PMID: 25152627
surgical intensive care unit; ventilator-associated pneumonia; device-related incidence rate; drug resistant organism; Acinetobacter baumannii
5.  Impact of surveillance of hospital-acquired infections on the incidence of ventilator-associated pneumonia in intensive care units: a quasi-experimental study 
Critical Care  2012;16(4):R161.
The preventive impact of hospital-acquired infection (HAI) surveillance is difficult to assess. Our objective was to investigate the effect of HAI surveillance disruption on ventilator-associated pneumonia (VAP) incidence.
A quasi-experimental study with an intervention group and a control group was conducted between 1 January 2004 and 31 December 2010 in two intensive care units (ICUs) of a university hospital that participated in a national HAI surveillance network. Surveillance was interrupted during the year 2007 in unit A (intervention group) and was continuous in unit B (control group). Period 1 (pre-test period) comprised patients hospitalized during 2004 to 2006, and period 2 (post-test period) involved patients hospitalized during 2008 to 2010. Patients hospitalized ≥48 hours and intubated during their stay were included. Multivariate Poisson regression was fitted to ascertain the influence of surveillance disruption.
A total of 2,771 patients, accounting for 19,848 intubation-days at risk, were studied; 307 had VAP. The VAP attack rate increased in unit A from 7.8% during period 1 to 17.1% during period 2 (P <0.001); in unit B, it was 7.2% and 11.2% for the two periods respectively (P = 0.17). Adjusted VAP incidence rose in unit A after surveillance disruption (incidence rate ratio = 2.17, 95% confidence interval 1.05 to 4.47, P = 0.036), independently of VAP trend; no change was observed in unit B. All-cause mortality and length of stay increased (P = 0.028 and P = 0.038, respectively) in unit A between periods 1 and 2. In unit B, no change in mortality was observed (P = 0.22), while length of stay decreased between periods 1 and 2 (P = 0.002).
VAP incidence, length of stay and all-cause mortality rose after HAI surveillance disruption in ICU, which suggests a specific effect of HAI surveillance on VAP prevention and reinforces the role of data feedback and counselling as a mechanism to facilitate performance improvement.
PMCID: PMC3580751  PMID: 22909033
6.  Impact of intensive care unit-acquired infection on hospital mortality in Japan: A multicenter cohort study 
To elucidate factors associated with hospital mortality in intensive care unit (ICU) patients and to evaluate the impact of ICU-acquired infection on hospital mortality in the context of the drug resistance of pathogens.
By using the Japanese Nosocomial Infection Surveillance (JANIS) database, 7,374 patients who were admitted to the 34 participating ICUs between July 2000 and May 2002, were aged 16 years or older, and who stayed in the ICU for 48 to 1,000 hours, did not transfer to another ICU, and did not become infected within 2 days after ICU admission, were followed up until hospital discharge or to Day 180 after ICU discharge. Adjusted hazard ratios (HRs) with the 95% confidence intervals (CIs) for hospital mortality were calculated using Cox’s proportional hazard model.
After adjusting for sex, age, and severity-of-illness (APACHE II score), a significantly higher HR for hospital mortality was found in ventilator use, central venous catheter use, and ICU-acquired drug-resistant infection, with a significantly lower HR in elective or urgent operations and urinary catheter use. The impact of ICU-acquired infection on hospital mortality was different between drug-susceptible pathogens (HR 1.11,95% CI:0.94–1.31) and drug-resistant pathogens (HR 1.42,95% CI: 1.15–1.77).
The use of a ventilator or a central venous catheter, and ICU-acquired drug-resistant infection were associated with a high risk of hospital mortality in ICU patients. The potential impact on hospital mortality emphasizes the importance of preventive measures against ICU-acquired infections, especially those caused by drug-resistant pathogens.
PMCID: PMC2723393  PMID: 21432299
multicenter cohort study; hospital mortality; ICU; nosocomial infection; drug resistance
7.  Acinetobacter baumannii nosocomial pneumonia: is the outcome more favorable in non-ventilated than ventilated patients? 
BMC Infectious Diseases  2013;13:142.
Acinetobacter baumannii hospital-acquired pneumonia (HAP) is associated with a high mortality worldwide. Non-ventilated patients with HAP (NVHAP) caused by nosocomial pathogens are reported to have a more favorable outcome than those with ventilator-associated pneumonia (VAP). The current study was designed to determine whether bacteremic patients with A. baumannii NVHAP also have a lower mortality than those receiving assisted ventilation.
This retrospective 10-year study was conducted at a 2900-bed teaching hospital located in Northern Taiwan. The population consisted of 144 patients with A. baumannii bacteremia and HAP. Of these 96 had VAP and 48 had NVHAP. Charts were reviewed for demographic characteristics, comorbidities, clinical manifestations, antimicrobial susceptibility, and 14-day mortality. Clonal relationships were determined by molecular typing.
There were no significant differences between the two groups in comorbidities (Charlson scores). Patients with NVHAP were more likely to have developed bacteremia earlier, outside the ICU and undergone fewer invasive procedures. They had significantly lower APACHE II scores, fewer bilateral pneumonias and lower rates of antimicrobial resistance. No specific clones were identified in either group. The unadjusted (crude) 14-day mortality rates were not significantly different between the groups (NVHAP 43.8% vs. VAP 31.3%, p = 0.196). The adjusted 14-day mortality risk was significantly lower in ventilator-assisted patients (odds ratio = 0.201; 95% confidence interval = 0.075-0.538; p = 0.001).
Patients with bacteremic NVHAP and VAP caused by A. baumannii had similar crude mortality rates, but on logistic regression analysis those receiving ventilator assistance had a significantly lower mortality. This may have been due to better airway protection, more intensive monitoring with earlier diagnosis and treatment in patients with VAP, greater innate susceptibility to infection in those with NVHAP and differences in the virulence of A. baumannii.
PMCID: PMC3605360  PMID: 23509931
Acinectobacter baumannii; Pneumonia; Hospital acquired; Ventilator
8.  Health-care-associated infections: Risk factors and epidemiology from an intensive care unit in Northern India 
Indian Journal of Anaesthesia  2014;58(1):30-35.
Background and Aims:
Health-care-associated infection is a key factor determining the clinical outcome among patients admitted in critical care areas. The objective of the study was to ascertain the epidemiology and risk factors of health-care-associated infections in Intensive Care Units (ICUs) in a tertiary care hospital.
This prospective, observational clinical study included patients admitted in ICU over a period of one and a half years. Routine surveillance of various health-care-associated infections such as catheter-associated urinary tract infections (CAUTI), central-line-associated blood stream infections (CLABSI), and ventilator-associated pneumonias (VAP) was done by the Department of Microbiology through specific Infection Surveillance Proforma.
Out of 679 patients, 166 suffered 198 episodes of device-associated infections. The infections included CAUTI, CLABSI, and VAP. The number of urinary tract infection (UTI) episodes was found to be 73 (10.75%) among the ICU patients who had indwelling urinary catheter. In addition, for 1 year CAUTI was calculated as 9.08/1000 catheter days. The number of episodes of blood stream infection was 86 (13.50%) among ICU patients having central line catheters. Also, CLABSI was found to be 13.86/1000 central line days. A total of 39 episodes (6.15%) of VAP was found in ICU patients over 18 months and VAP present for 6.04/1000 ventilator days.
The organisms most commonly associated with health-care-associated infections were Pseudomonas aeruginosa and Acinetobacter species. The risk factors identified as being significantly associated with device associated infections in our ICU were diabetes, COPD and ICU stay for ≥8 days (P < 0.05).
PMCID: PMC3968648  PMID: 24700896
Epidemiology; health-care-associated infection; risk factors
9.  Impact of ureido/carboxypenicillin resistance on the prognosis of ventilator-associated pneumonia due to Pseudomonas aeruginosa 
Critical Care  2011;15(2):R112.
Although Pseudomonas aeruginosa is a leading pathogen responsible for ventilator-associated pneumonia (VAP), the excess in mortality associated with multi-resistance in patients with P. aeruginosa VAP (PA-VAP), taking into account confounders such as treatment adequacy and prior length of stay in the ICU, has not yet been adequately estimated.
A total of 223 episodes of PA-VAP recorded into the Outcomerea database were evaluated. Patients with ureido/carboxy-resistant P. aeruginosa (PRPA) were compared with those with ureido/carboxy-sensitive P. aeruginosa (PSPA) after matching on duration of ICU stay at VAP onset and adjustment for confounders.
Factors associated with onset of PRPA-VAP were as follows: admission to the ICU with septic shock, broad-spectrum antimicrobials at admission, prior use of ureido/carboxypenicillin, and colonization with PRPA before infection. Adequate antimicrobial therapy was more often delayed in the PRPA group. The crude ICU mortality rate and the hospital mortality rate were not different between the PRPA and the PSPA groups. In multivariate analysis, after controlling for time in the ICU before VAP diagnosis, neither ICU death (odds ratio (OR) = 0.73; 95% confidence interval (CI): 0.32 to 1.69; P = 0.46) nor hospital death (OR = 0.87; 95% CI: 0.38 to 1.99; P = 0.74) were increased in the presence of PRPA infection. This result remained unchanged in the subgroup of 87 patients who received adequate antimicrobial treatment on the day of VAP diagnosis.
After adjustment, and despite the more frequent delay in the initiation of an adequate antimicrobial therapy in these patients, resistance to ureido/carboxypenicillin was not associated with ICU or hospital death in patients with PA-VAP.
PMCID: PMC3219393  PMID: 21481266
10.  Guideline-adherent initial intravenous antibiotic therapy for hospital-acquired/ventilator-associated pneumonia is clinically superior, saves lives and is cheaper than non guideline adherent therapy 
Hospital-acquired pneumonia (HAP) often occurring as ventilator-associated pneumonia (VAP) is the most frequent hospital infection in intensive care units (ICU). Early adequate antimicrobial therapy is an essential determinant of clinical outcome. Organisations like the German PEG or ATS/IDSA provide guidelines for the initial calculated treatment in the absence of pathogen identification. We conducted a retrospective chart review for patients with HAP/VAP and assessed whether the initial intravenous antibiotic therapy (IIAT) was adequate according to the PEG guidelines
Materials and methods
We collected data from 5 tertiary care hospitals. Electronic data filtering identified 895 patients with potential HAP/VAP. After chart review we finally identified 221 patients meeting the definition of HAP/VAP. Primary study endpoints were clinical improvement, survival and length of stay. Secondary endpoints included duration of mechanical ventilation, total costs, costs incurred on the intensive care unit (ICU), costs incurred on general wards and drug costs.
We found that 107 patients received adequate initial intravenous antibiotic therapy (IIAT) vs. 114 with inadequate IIAT according to the PEG guidelines. Baseline characteristics of both groups revealed no significant differences and good comparability. Clinical improvement was 64% over all patients and 82% (85/104) in the subpopulation with adequate IIAT while only 47% (48/103) inadequately treated patients improved (p < 0.001). The odds ratio of therapeutic success with GA versus NGA treatment was 5.821 (p < 0.001, [95% CI: 2.712-12.497]). Survival was 80% for the total population (n = 221), 86% in the adequately treated (92/107) and 74% in the inadequately treated 'subpopulation (84/114) (p = 0.021). The odds ratio of mortality for GA vs. NGA treatment was 0.565 (p = 0.117, [95% CI: 0.276-1.155]). Adequately treated patients had a significantly shorter length of stay (LOS) (23.9 vs. 28.3 days; p = 0.022), require significantly less hours of mechanical ventilation (175 vs. 274; p = 0.001), incurred lower total costs (EUR 28,033 vs. EUR 36,139, p = 0.006) and lower ICU-related costs (EUR 13,308 vs. EUR 18,666, p = 0.003).
Drug costs for the hospital stay were also lower (EUR 4,069 vs. EUR 4,833) yet not significant. The most frequent types of inadequate therapy were monotherapy instead of combination therapy, wrong type of penicillin and wrong type of cephalosporin.
These findings are consistent with those from other studies analyzing the impact of guideline adherence on survival rates, clinical success, LOS and costs. However, inadequately treated patients had a higher complicated pathogen risk score (CPRS) compared to those who received adequate therapy. This shows that therapy based on local experiences may be sufficient for patients with low CPRS but inadequate for those with high CPRS. Linear regression models showed that single items of the CPRS like extrapulmonary organ failure or late onset had no significant influence on the results.
Guideline-adherent initial intravenous antibiotic therapy is clinically superior, saves lives and is less expensive than non guideline adherent therapy. Using a CPRS score can be a useful tool to determine the right choice of initial intravenous antibiotic therapy. the net effect on the German healthcare system per year is estimated at up to 2,042 lives and EUR 125,819,000 saved if guideline-adherent initial therapy for HAP/VAP were established in all German ICUs.
PMCID: PMC3352003  PMID: 21813372
11.  Impact of four sequential measures on the prevention of ventilator-associated pneumonia in cardiac surgery patients 
Critical Care  2014;18(2):R53.
Ventilator-associated pneumonia (VAP) is the most frequent infection in patients admitted to intensive care units.
The efficacy of individual measures for the prevention of VAP is well documented, and data on the impact of implementing bundle measures have usually been reported from studies in which several measures are implemented simultaneously in the general intensive care unit (ICU).
The objective of our work was to evaluate the impact of four sequentially implemented measures for preventing VAP in a major heart surgery ICU. The measures were a specific training program, aspiration of subglottic secretions (ASSs), introduction of an inclinometer to improve the semirecumbent position, and reinforcement of oral care with chlorhexidine.
We compared rates of VAP, days on mechanical ventilation (MV), and cost of antimicrobial agents before and during implementation.
We collected data from 401 patients before the intervention and from 1,534 patients during the intervention. Both groups were comparable. No significant differences in EuroSCORE were observed between the patients of both periods (6.4 versus 6.3; P = 0.7). The rates of VAP (episodes/1,000 days of ventilation) were, respectively, 23.9 versus 13.5 (P = 0.005). Mean number of days of MV/1,000 days of stay was 507 versus 375 (P = 0.001), and the cost of antimicrobial therapy (Euros/1,000 days of stay) was €70,612 versus €52,775 (P = 0.10). The main effect of sequential application of preventive measures in time achieved a relative-rate reduction of VAP of 41% (IRR, 0.41; 95% CI, 0.28 to 0.62). The mortality rate before and during the intervention was 13.0% and 10.2%, respectively.
VAP rate was most significantly reduced by training and the use of the inclinometer.
A sequentially applied bundle of four preventive measures reduces VAP rates, days of MV, and the cost of antimicrobial therapy in patients admitted to the major heart surgery ICU.
Trial registration
Clinical NCT02060045. Registered 4 February 2014.
PMCID: PMC4056787  PMID: 24667011
12.  A risk factor analysis of healthcare-associated fungal infections in an intensive care unit: a retrospective cohort study 
The incidence of fungal healthcare-associated infection (HAI) has increased in a major teaching hospital in the northern part of Taiwan over the past decade, especially in the intensive care units (ICUs). The purpose of this study was to determine the factors that were responsible for the outbreak and trend in the ICU.
Surveillance fungal cultures were obtained from “sterile” objects, antiseptic solutions, environment of infected patients and hands of medical personnel. Risk factors for comparison included age, gender, admission service, and total length of stay in the ICU, Acute Physiology and Chronic Health Evaluation (APACHE) II scores at admission to the ICU, main diagnosis on ICU admission, use of invasive devices, receipt of hemodialysis, total parenteral nutrition (TPN) use, history of antibiotic therapy before HAI or during ICU stay in no HAI group, and ICU discharge status (ie, dead or alive). Univariable analysis followed by multiple logistic regression analysis was performed to identify the independent risk factors for ICU fungal HAIs and ICU mortality.
There was a significant trend in ICU fungal HAIs from 1998 to 2009 (P < 0.001). A total of 516 episodes of ICU fungal HAIs were identified; the rates of various infections were urinary tract infection (UTI) (54.8%), blood stream infection (BSI) (30.6%), surgical site infection (SSI) (6.6%), pneumonia (4.5%), other sites (3.5%). The fungi identified were: yeasts (54.8%), Candida albicans (27.3%), Candida tropicalis (6.6%), Candida glabrata (6.6%), Candida parapsilosis (1.9%), Candida species (0.8%), and other fungi (1.9%). Candida albicans accounted for 63% of all Candida species. Yeasts were found in the environment of more heavily infected patients. The independent risk factors (P < 0.05) of developing ICU fungal HAIs from all sites were TPN use, sepsis, surgical patients, mechanical ventilation and an indwelling urinary catheter. The independent risk factors for ICU fungal UTI included TPN use, mechanical ventilation and an indwelling urinary catheter. The independent risk factors for ICU fungal BSI included TPN use, sepsis, and higher APACHE II score. The independent risk factors for ICU fungal pneumonia included TPN use, surgical patients. The independent risk factors for ICU fungal SSI included surgical patients, and TPN use. The odds ratios of TPN use in various infection types ranged from 3.51 to 8.82. The risk of mortality in patients with ICU fungal HAIs was over 2 times that of patients without ICU HAIs in the multiple logistic regression analysis (P < 0.001).
There was a secular trend of an increasing number of fungal HAIs in our ICU over the past decade. Patients with ICU fungal HAIs had a significantly higher mortality rate than did patients without ICU HAIs. Total parenteral nutrition was a significant risk factor for all types of ICU fungal HAIs, and its use should be monitored closely.
PMCID: PMC3548709  PMID: 23298156
Intensive care unit; Fungal infection; Outbreak surveillance; Candida; Total parenteral nutrition
13.  Epidemiologic surveillance of nosocomial infections in a Pediatric Intensive Care Unit of a developing country 
BMC Pediatrics  2010;10:66.
Nosocomial Infections (NI) are a frequent and relevant problem. The purpose of this study was to determine the epidemiology of the three most common NI in a Pediatric Intensive Care Unit from a developing country.
We performed a prospective study in a single Pediatric Intensive Care Unit during 12 months. Children were assessed for 3 NI: bloodstream infections (BSI), ventilator-associated pneumonia (VAP) and urinary tract infections (UTI), according to Center for Disease Control criteria. Use of devices (endotracheal tube [ETT], central venous catheter [CVC] and urinary catheter [UC]) was recorded.
Four hundred fourteen patients were admitted; 81 patients (19.5%) developed 85 NIs. Density of incidence of BSI, VAP and UTI was 18.1, 7.9 and 5.1/1000 days of use of CVC, ETT and UC respectively. BSI was more common in children with CVCs than in those without CVCs (20% vs. 4.7%, p < 0.05). Candida spp. was the commonest microorganism in BSI (41%), followed by Coagulase-negative Staphylococcus (17%). Pseudomonas (52%) was the most common germ for VAP and Candida (71%) for UTI. The presence of NI was associated with increased mortality (38.2% vs. 20.4% in children without NI; p < 0.001) and the median length of ICU stay (23 vs. 6 days in children without NI; p < 0.001). Children with NI had longer average hospital stay previous to diagnosis of this condition (12.3 vs. 6 days; p < 0.001).
One of every 5 children acquires an NI in the PICU. Its presence was associated with increased mortality and length of stay. At the same time a longer stay was associated with an increased risk of developing NI.
PMCID: PMC2944329  PMID: 20831797
14.  Incidence of healthcare associated infection in the surgical ICU of a tertiary care hospital 
Healthcare associated infections (HAI) have taken on a new dimension with outbreaks of increasingly resistant organisms becoming common. Protocol-based infection control practices in the intensive care unit (ICU) are extremely important. Moreover, baseline information of the incidence of HAI helps in planning-specific interventions at infection control.
This hospital-based observational study was carried out from Dec 2009 to May 2010 in the 10-bedded surgical intensive care unit of a tertiary care hospital. CDC HAI definitions were used to diagnose HAI.
A total of 293 patients were admitted in the ICU. 204 of these were included in the study. 36 of these patients developed HAI with a frequency of 17.6%. The incidence rate (IR) of catheter-related blood stream infections (CRBSI) was 16/1000 Central Venous Catheter (CVC) days [95% C.I. 9–26]. Catheter-associated urinary tract infections (CAUTI) 9/1000 urinary catheter days [95% C.I. 4–18] and ventilator-associated pneumonias (VAP) 32/1000 ventilator days [95% confidence interval 22–45].
The HAI rates in our ICU are less than other hospitals in developing countries. The incidence of VAP is comparable to other studies. Institution of an independent formal infection control monitoring and surveillance team to monitor & undertake infection control practices is an inescapable need in service hospitals.
PMCID: PMC3862707  PMID: 24600084
Hospital acquired infections; ICU care; Infection control
15.  Association of compliance of ventilator bundle with incidence of ventilator-associated pneumonia and ventilator utilization among critical patients over 4 years 
Annals of Thoracic Medicine  2014;9(4):221-226.
Several studies showed that the implementation of the Institute for Healthcare Improvement (IHI) ventilator bundle alone or with other preventive measures are associated with reducing Ventilator-Associated Pneumonia (VAP) rates. However, the association with ventilator utilization was rarely examined and the findings were conflicting. The objectives were to validate the bundle association with VAP rate in a traditionally high VAP environment and to examine its association with ventilator utilization.
The study was conducted at the adult medical-surgical intensive care unit (ICU) at King Abdulaziz Medical City, Saudi Arabia, between 2010 and 2013. VAP data were collected by a prospective targeted surveillance as per Centers for Disease Control and Prevention (CDC)/National Healthcare Safety Network (NHSN) methodology while bundle data were collected by a cross-sectional design as per IHI methodology.
Ventilator bundle compliance significantly increased from 90% in 2010 to 97% in 2013 (P for trend < 0.001). On the other hand, VAP rate decreased from 3.6 (per 1000 ventilator days) in 2010 to 1.0 in 2013 (P for trend = 0.054) and ventilator utilization ratio decreased from 0.73 in 2010 to 0.59 in 2013 (P for trend < 0.001). There were negative significant correlations between the trends of ventilator bundle compliance and VAP rate (cross-correlation coefficients −0.63 to 0.07) and ventilator utilization (cross-correlation coefficients −0.18 to −0.63).
More than 70% improvement of VAP rates and approximately 20% improvement of ventilator utilization were observed during IHI ventilator bundle implementation among adult critical patients in a tertiary care center in Saudi Arabia. Replicating the current finding in multicenter randomized trials is required before establishing any causal link.
PMCID: PMC4166069  PMID: 25276241
Bundle; health-care-associated infection; Institute for Healthcare Improvement; quality improvement; ventilator-associated pneumonia; ventilator utilization
16.  Ventilator-associated pneumonia in a tertiary care intensive care unit: Analysis of incidence, risk factors and mortality 
Ventilator-associated pneumonia (VAP) is the most common nosocomial infection diagnosed in the intensive care unit (ICU) and in spite of advances in diagnostic techniques and management it remains a common cause of hospital morbidity and mortality.
The primary objective of the following study is to determine the incidence, various risk factors and attributable mortality associated with VAP and secondary objective is to identify the various bacterial pathogens causing VAP in the ICU.
Materials and Methods:
This prospective observational study was carried out over a period of 1 year. VAP was diagnosed using the clinical pulmonary infection score. Endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) samples of suspected cases of VAP were collected from ICU patients and processed as per standard protocols.
Statistical Analysis:
Fisher's exact test was applied when to compare two or more set of variables were compared.
The incidence of VAP in our study was 57.14% and the incidence density of VAP was 31.7/1000 ventilator days. Trauma was the commonest underlying condition associated with VAP. The incidence of VAP increased as the duration of mechanical ventilation increased and there was a total agreement in bacteriology between semi-quantitative ETAs and BALs in our study. The overall mortality associated with VAP was observed to be 48.33%.
The incidence of VAP was 57.14%. Study showed that the incidence of VAP is directly proportional to the duration of mechanical ventilation. The most common pathogens causing VAP were Acinetobacter spp. and Pseudomonas aeruginosa and were associated with a high fatality rate.
PMCID: PMC4033852  PMID: 24872648
Incidence; intensive care unit; mortality; risk factors; ventilator-associated pneumonia
17.  Staffing level: a determinant of late-onset ventilator-associated pneumonia 
Critical Care  2007;11(4):R80.
The clinical and economic burden of ventilator-associated pneumonia (VAP) is uncontested. We conducted the present study to determine whether low nurse-to-patient ratio increases the risk for VAP and whether this effect is similar for early-onset and late-onset VAP.
This prospective, observational, single-centre cohort study was conducted in the medical intensive care unit (ICU) of the University of Geneva Hospitals. All patients who were at risk for ICU-acquired infection admitted from January 1999 to December 2002 were followed from admission to discharge. Collected variables included patient characteristics, admission diagnosis, Acute Physiology and Chronic Health Evaluation II score, co-morbidities, exposure to invasive devices, daily number of patients and nurses on duty, nurse training level and all-site ICU-acquired infections. VAP was diagnosed using standard definitions.
Among 2,470 patients followed during their ICU stay, 262 VAP episodes were diagnosed in 209/936 patients (22.3%) who underwent mechanical ventilation. Median duration of mechanical ventilation was 3 days (interquartile range 2 to 6 days) among patients without VAP and 11 days (6 to 19 days) among patients with VAP. Late-onset VAP accounted for 61% of all episodes. The VAP rate was 37.6 episodes per 1,000 days at risk (95% confidence interval 33.2 to 42.4). The median daily nurse-to-patient ratio over the study period was 1.9 (interquartile range 1.8 to 2.2). By multivariate Cox regression analysis, we found that a high nurse-to-patient ratio was associated with a decreased risk for late-onset VAP (hazard ratio 0.42, 95% confidence interval 0.18 to 0.99), but there was no association with early-onset VAP.
Lower nurse-to-patient ratio is associated with increased risk for late-onset VAP.
PMCID: PMC2206525  PMID: 17640384
18.  Epidemiology of ventilator-associated tracheobronchitis and vantilator-associated pneumonia in patients with inhalation injury at the Burn Centre in Brno (Czech Republic) 
Aim. The aim of this work is to determine the incidence of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) and to define the define the most important respiratory pathogens in patients with inhalation injury. Introduction. Infectious complications in severely burned patients present serious problems. Patients with inhalation injuries are exposed to greater risk owing to the possible development of infectious complications in the lower respiratory tract. VAP is the predominant cause of death in these patients. This is due to the increasing resistance of strains of Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Design. Retrospective, monocentric. Setting. A five-bed burn intensive care unit. Material and methods. Between 2004 and 2009, 348 adult patients were hospitalized in the intensive care unit of the Department of Burns and Reconstructive Surgery, Brno University Hospital, Czech Republic. Of these, 127 (36.49%) were diagnosed by bronchoscopy as having inhalation injury. The prerequisite for inclusion in the cohort was an inhalation injury requiring artificial ventilation for at least 48 h. The lower airway microbiological condition was monitored regularly by sampling biological material for cultures (sputum, tracheobronchial aspirates, etc.). For the diagnosis of VAP and VAT we used the Centers for Disease Control and Prevention criteria and the Clinical Pulmonary Infection Score. Results. The average age of the 127 patients (31 women/96 men) included in the study was 38.4 yr (range, 21-69 yr) and the average total body surface area (TBSA) burned was 29.3% (range, 2-75%). The average length of hospital stay was 49.4 days (range, 4-150 days) and the duration of mechanical ventilation 8.7 days; 18 patients (14.2%) died. In patients with inhalation injury, 309 strains of bacteria were cultivated from the lower respiratory tract, of which 234 were Gram-negative. All of these bacterial strains were isolated in significant quantities for lower respiratory tract infection. The most common bacteria isolated from the lower respiratory tract was Klebsiella pneumoniae (78 times), followed by Pseudomonas aeruginosa (49x), and Acinetobacter baumannii (28x). VAT was diagnosed in 109 patients (85.8%) in the cohort. The incidence of VAT was calculated to be 98.8 per 1000 days of mechanical ventilation. VAP was diagnosed in 34 patients in the cohort (26.8%). The incidence of VAP was calculated as being 30.8 cases per 1,000 days of mechanical ventilation. In eight patients (23.5%), VAP was diagnosed within 5 days of initiation of mechanical ventilation (early onset) and in 26 patients (76.5%) after a longer period (late onset). The most common aetiological agent of VAT and VAP was Klebsiella pneumoniae (respectively 41.3% and 35.3%). Conclusion. In this study we were able to determine the incidence of VAP and VAT in patients with inhalation injury. In spite of the advances in diagnostics and therapy, inhalation injury is still burdened with disappointingly high morbidity and mortality rates. For this reason, the treatment of VAP remains a major challenge for all physicians caring for patients with inhalation injury.
PMCID: PMC3293227  PMID: 22396669
inhalation injury; ventilator-associated pneumonia; ventilator-associated tracheobronchitis; Gram-negative bacterial strains; resistance
19.  Use of ventilator associated pneumonia bundle and statistical process control chart to decrease VAP rate in Syria 
Avicenna Journal of Medicine  2012;2(4):79-83.
Implementation of ventilator associated pneumonia (VAP) bundle as a performance improvement project in the critical care units for all mechanically ventilated patients aiming to decrease the VAP rates.
VAP bundle was implemented in 4 teaching hospitals after educational sessions and compliance rates along with VAP rates were monitored using statistical process control charts.
VAP bundle compliance rates were steadily increasing from 33 to 80% in hospital 1, from 33 to 86% in hospital 2 and from 83 to 100% in hospital 3 during the study period. The VAP bundle was not applied in hospital 4 therefore no data was available. A target level of 95% was reached only in hospital 3. This correlated with a decrease in VAP rates from 30 to 6.4 per 1000 ventilator days in hospital 1, from 12 to 4.9 per 1000 ventilator days in hospital 3, whereas VAP rate failed to decrease in hospital 2 (despite better compliance) and it remained high around 33 per 1000 ventilator days in hospital 4 where VAP bundle was not implemented
VAP bundle has performed differently in different hospitals in our study. Prevention of VAP requires a multidimensional strategy that includes strict infection control interventions, VAP bundle implementation, process and outcome surveillance and education.
PMCID: PMC3696204  PMID: 23826553
Bundle; mechanical ventilation; prevention; ventilator associated pneumonia
20.  Ventilator-associated pneumonia 
The Australasian Medical Journal  2014;7(8):334-344.
Ventilator-associated pneumonia (VAP) is a type of nosocomial pneumonia that occurs in patients who receive mechanical ventilation (MV). According to the International Nosocomial Infection Control Consortium (INICC), the overall rate of VAP is 13.6 per 1,000 ventilator days. The incidence varies according to the patient group and hospital setting. The incidence of VAP ranges from 13–51 per 1,000 ventilation days. Early diagnosis of VAP with appropriate antibiotic therapy can reduce the emergence of resistant organisms.
The aim of this review was to provide an overview of the incidence, risk factors, aetiology, pathogenesis, treatment, and prevention of VAP. A literature search for VAP was done through the PUBMED/MEDLINE database. This review outlines VAP’s risk factors, diagnostic methods, associated organisms, and treatment modalities.
VAP is a common nosocomial infection associated with ventilated patients. The mortality associated with VAP is high. The organisms associated with VAP and their resistance pattern varies depending on the patient group and hospital setting. The diagnostic methods available for VAP are not universal; however, a proper infection control policy with appropriate antibiotic usage can reduce the mortality rate among ventilated patients.
PMCID: PMC4157153  PMID: 25279009
Ventilator-associated pneumonia; mechanical ventilation; clinical pulmonary infection score
21.  The Epidemiology of Ventilator-Associated Pneumonia in a Network of Community Hospitals: A Prospective Multicenter Study 
To describe the epidemiology of ventilator-associated pneumonia (VAP) in community hospitals.
Prospective study in 31 community hospitals from 2007 to 2011.
VAP surveillance was performed by infection preventionists using the National Healthcare Safety Network protocol. VAP incidence was reported as number of events per 1,000 ventilator-days. We categorized hospitals into small (<30,000 patient-days/year), medium (30,000–60,000 patient-days/year), and large (>60,000 patient-days/year) groups and compared VAP incidence by hospital size.
The median VAP incidence was 1.4 (interquartile range, 0.4–2.4), and ventilator utilization ratio (VUR) was 0.33 (0.25–0.47). VAP incidence was higher in small hospitals (2.1) than medium (0.85) or large (0.69) hospitals (P = .03) despite a lower VUR in small hospitals (0.29 vs 0.31 vs 0.44, respectively; P = .01). The median age of 247 VAP cases was 64 (53–73); 136 (55.1%) were female; 142 (57.5%) were Caucasian; 170 (68.8%) were admitted from home. The length of stay and duration of ventilation were 26 (14–42) and 12 (4–21) days, respectively. The pre- and postinfection hospital stays were 8 (3–13) days and 14 (8–30) days, respectively. Data on outcomes were available in 214 cases (86.6%), and 75 (35.0%) cases died during hospitalization. The top 3 pathogens were methicillin-resistant Staphylococcus aureus (MRSA; n = 70, 27.9%), Pseudomonas species (n = 40, 16.3%), and Klebsiella species (n = 34, 13.3%).
VAP incidence was inversely associated with size of hospital. VAP in community hospitals was frequently caused by MRSA. Importantly, predictors of VAP incidence in tertiary care hospitals such as VUR may not be predictive in community hospitals with few ventilated patients.
PMCID: PMC3977705  PMID: 23739068
22.  Intensive care unit-acquired urinary tract infections in a regional critical care system 
Critical Care  2005;9(2):R60-R65.
Few studies have evaluated urinary tract infections (UTIs) specifically acquired within intensive care units (ICUs), and the effect of such infections on patient outcome is unclear. The objectives of this study were to describe the occurrence, microbiology, and risk factors for acquiring UTIs in the ICU and to determine whether these infections independently increase mortality.
A surveillance cohort study was conducted among all adults admitted to multi-system and cardiovascular surgery ICUs in the Calgary Health Region (CHR, population about 1 million) between 1 January 2000 and 31 December 2002.
During the 3 years, 4465 patients were admitted 4915 times to a CHR ICU for 48 hours or more. A total of 356 ICU-acquired UTIs (defined as at least 105 colony-forming units/ml of one or two organisms 48 hours or more after ICU admission) occurred among 290 (6.5%) patients, yielding an overall incidence density of ICU-acquired UTIs of 9.6 per 1000 ICU days. Four bacteremic/fungemic ICU-acquired UTIs occurred (0.1 per 1000 ICU days). Development of an ICU-acquired UTI was more common in women (relative risk [RR] 1.58; 95% confidence interval [CI] 1.43–1.75; P < 0.0001) and in medical (9%) compared with non-cardiac surgical (6%), and cardiac surgical patients (2%). The most common organisms isolated were Escherichia coli (23%), Candida albicans (20%), and Enterococcus species (15%). Antibiotic-resistant organisms were identified among 14% isolates. Although development of an ICU-acquired UTI was associated with significantly higher crude in-hospital mortality (86/290 [30%] vs. 862/4167 [21%]; RR = 1.43; 95% CI 1.19–1.73; P < 0.001); an ICU-acquired UTI was not an independent predictor for death.
Development of an ICU-acquired UTI is common in critically ill patients. Although a marker of increased morbidity associated with critical illness, it is not a significant attributable cause of mortality.
PMCID: PMC1175915  PMID: 15774051
incidence; intensive care unit; mortality; urinary tract infection
23.  Multicenter Evaluation of a Novel Surveillance Paradigm for Complications of Mechanical Ventilation 
PLoS ONE  2011;6(3):e18062.
Ventilator-associated pneumonia (VAP) surveillance is time consuming, subjective, inaccurate, and inconsistently predicts outcomes. Shifting surveillance from pneumonia in particular to complications in general might circumvent the VAP definition's subjectivity and inaccuracy, facilitate electronic assessment, make interfacility comparisons more meaningful, and encourage broader prevention strategies. We therefore evaluated a novel surveillance paradigm for ventilator-associated complications (VAC) defined by sustained increases in patients' ventilator settings after a period of stable or decreasing support.
We assessed 600 mechanically ventilated medical and surgical patients from three hospitals. Each hospital contributed 100 randomly selected patients ventilated 2–7 days and 100 patients ventilated >7 days. All patients were independently assessed for VAP and for VAC. We compared incidence-density, duration of mechanical ventilation, intensive care and hospital lengths of stay, hospital mortality, and time required for surveillance for VAP and for VAC. A subset of patients with VAP and VAC were independently reviewed by a physician to determine possible etiology.
Of 597 evaluable patients, 9.3% had VAP (8.8 per 1,000 ventilator days) and 23% had VAC (21.2 per 1,000 ventilator days). Compared to matched controls, both VAP and VAC prolonged days to extubation (5.8, 95% CI 4.2–8.0 and 6.0, 95% CI 5.1–7.1 respectively), days to intensive care discharge (5.7, 95% CI 4.2–7.7 and 5.0, 95% CI 4.1–5.9), and days to hospital discharge (4.7, 95% CI 2.6–7.5 and 3.0, 95% CI 2.1–4.0). VAC was associated with increased mortality (OR 2.0, 95% CI 1.3–3.2) but VAP was not (OR 1.1, 95% CI 0.5–2.4). VAC assessment was faster (mean 1.8 versus 39 minutes per patient). Both VAP and VAC events were predominantly attributable to pneumonia, pulmonary edema, ARDS, and atelectasis.
Screening ventilator settings for VAC captures a similar set of complications to traditional VAP surveillance but is faster, more objective, and a superior predictor of outcomes.
PMCID: PMC3062570  PMID: 21445364
24.  Costs and risk factors for ventilator-associated pneumonia in a Turkish University Hospital's Intensive Care Unit: A case-control study 
Ventilator-associated pneumonia (VAP) which is an important part of all nosocomial infections in intensive care unit (ICU) is a serious illness with substantial morbidity and mortality, and increases costs of hospital care. We aimed to evaluate costs and risk factors for VAP in adult ICU.
This is a-three year retrospective case-control study. The data were collected between 01 January 2000 and 31 December 2002. During the study period, 132 patients were diagnosed as nosocomial pneumonia of 731 adult medical-surgical ICU patients. Of these only 37 VAP patients were assessed, and multiple nosocomially infected patients were excluded from the study. Sixty non-infected ICU patients were chosen as control patients.
Median length of stay in ICU in patients with VAP and without were 8.0 (IQR: 6.5) and 2.5 (IQR: 2.0) days respectively (P < 0.0001). Respiratory failure (OR, 11.8; 95%, CI, 2.2–62.5; P < 0.004), coma in admission (Glasgow coma scale < 9) (OR, 17.2; 95% CI, 2.7–107.7; P < 0.002), depressed consciousness (OR, 8.8; 95% CI, 2.9–62.5; P < 0.02), enteral feeding (OR, 5.3; 95% CI, 1.0–27.3; P = 0.044) and length of stay (OR, 1.3; 95% CI, 1.0–1.7; P < 0.04) were found as important risk factors. Most commonly isolated microorganism was methicillin resistant Staphylococcus aureus (30.4%). Mortality rates were higher in patients with VAP (70.3%) than the control patients (35.5%) (P < 0.003). Mean cost of patients with and without VAP were 2832.2+/-1329.0 and 868.5+/-428.0 US Dollars respectively (P < 0.0001).
Respiratory failure, coma, depressed consciousness, enteral feeding and length of stay are independent risk factors for developing VAP. The cost of VAP is approximately five-fold higher than non-infected patients.
PMCID: PMC419357  PMID: 15109397
ventilator-associated pneumonia; intensive care unit; risk factors; cost
25.  Mortality and Hospital Stay Associated with Resistant Staphylococcus aureus and Escherichia coli Bacteremia: Estimating the Burden of Antibiotic Resistance in Europe 
PLoS Medicine  2011;8(10):e1001104.
The authors calculate excess mortality, excess hospital stay, and related hospital expenditure associated with antibiotic-resistant bacterial bloodstream infections (Staphylococcus aureus and Escherichia coli) in Europe.
The relative importance of human diseases is conventionally assessed by cause-specific mortality, morbidity, and economic impact. Current estimates for infections caused by antibiotic-resistant bacteria are not sufficiently supported by quantitative empirical data. This study determined the excess number of deaths, bed-days, and hospital costs associated with blood stream infections (BSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) and third-generation cephalosporin-resistant Escherichia coli (G3CREC) in 31 countries that participated in the European Antimicrobial Resistance Surveillance System (EARSS).
Methods and Findings
The number of BSIs caused by MRSA and G3CREC was extrapolated from EARSS prevalence data and national health care statistics. Prospective cohort studies, carried out in hospitals participating in EARSS in 2007, provided the parameters for estimating the excess 30-d mortality and hospital stay associated with BSIs caused by either MRSA or G3CREC. Hospital expenditure was derived from a publicly available cost model. Trends established by EARSS were used to determine the trajectories for MRSA and G3CREC prevalence until 2015. In 2007, 27,711 episodes of MRSA BSIs were associated with 5,503 excess deaths and 255,683 excess hospital days in the participating countries, whereas 15,183 episodes of G3CREC BSIs were associated with 2,712 excess deaths and 120,065 extra hospital days. The total costs attributable to excess hospital stays for MRSA and G3CREC BSIs were 44.0 and 18.1 million Euros (63.1 and 29.7 million international dollars), respectively. Based on prevailing trends, the number of BSIs caused by G3CREC is likely to rapidly increase, outnumbering the number of MRSA BSIs in the near future.
Excess mortality associated with BSIs caused by MRSA and G3CREC is significant, and the prolongation of hospital stay imposes a considerable burden on health care systems. A foreseeable shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections will exacerbate this situation and is reason for concern.
Please see later in the article for the Editors' Summary
Editors' Summary
Antimicrobial resistance—a consequence of the use and misuse of antimicrobial medicines—occurs when a microorganism becomes resistant (usually by mutation or acquiring a resistance gene) to an antimicrobial drug to which it was previously sensitive. Then standard treatments become ineffective, leading to persistent infections, which may spread to other people. With some notable exceptions such as TB, HIV, malaria, and gonorrhea, most of the disease burden attributable to antimicrobial resistance is caused by hospital-associated infections due to opportunistic bacterial pathogens. These bacteria often cause life-threatening or difficult-to-manage conditions such as deep tissue, wound, or bone infections, or infections of the lower respiratory tract, central nervous system, or blood stream. The two most frequent causes of blood stream infections encountered worldwide are Staphylococcus aureus and Escherichia coli.
Why Was This Study Done?
Although hospital-associated infections have gained much attention over the past decade, the overall effect of this growing phenomenon on human health and medical services has still to be adequately quantified. The researchers proposed to fill this information gap by estimating the impact—morbidity, mortality, and demands on health care services—of antibiotic resistance in Europe for two types of resistant organisms that are typically associated with resistance to multiple classes of antibiotics and can be regarded as surrogate markers for multi-drug resistance—methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli.
What Did the Researchers Do and Find?
Recently, the Burden of Resistance and Disease in European Nations project collected representative data on the clinical impact of antimicrobial resistance throughout Europe. Using and combining this information with 2007 prevalence data from the European Antibiotic Resistance Surveillance System, the researchers calculated the burden of disease associated with methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli blood stream infections. This burden of disease was expressed as excess number of deaths, excess number of days in hospital, and excess costs. Using statistical models, the researchers predicted trend-based resistance trajectories up to 2015 for the 31 participating countries in the European region.
The researchers included 1,293 hospitals from the 31 countries, typically covering 47% of all available acute care hospital beds in most countries, in their analysis. For S. aureus, the estimated number of blood stream infections totaled 108,434, of which 27,711 (25.6%) were methicillin-resistant. E. coli caused 163,476 blood stream infections, of which 15,183 (9.3%) were resistant to third-generation cephalosporins. An estimated 5,503 excess deaths were associated with blood stream infections caused by methicillin-resistant S. aureus (with the UK and France predicted to experience the highest excess mortality), and 2,712 excess deaths with blood stream infections caused by third-generation cephalosporin-resistant E. coli (predicted to be the highest in Turkey and the UK). The researchers also found that blood stream infections caused by both methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli contributed respective excesses of 255,683 and 120,065 extra bed-days, accounting for an estimated extra cost of 62.0 million Euros (92.8 million international dollars). In their trend analysis, the researchers found that 97,000 resistant blood stream infections and 17,000 associated deaths could be expected in 2015, along with increases in the lengths of hospital stays and costs. Importantly, the researchers estimated that in the near future, the burden of disease associated with third-generation cephalosporin-resistant E. coli is likely to surpass that associated with methicillin-resistant S. aureus.
What Do These Findings Mean?
These findings show that even though the blood stream infections studied represent only a fraction of the total burden of disease associated with antibiotic resistance, excess mortality associated with these infections caused by methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli is high, and the associated prolonged length of stays in hospital imposes a considerable burden on health care systems in Europe. Importantly, a possible shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections is concerning. Such forecasts suggest that despite anticipated gains in the control of methicillin-resistant S. aureus, the increasing number of infections caused by third-generation cephalosporin-resistant Gram-negative pathogens, such as E. coli, is likely to outweigh this achievement soon. This increasing burden will have a big impact on already stretched health systems.
Additional Information
Please access these websites via the online version of this summary at
The World Health Organization has a fact sheet on general antimicrobial resistance
The US Centers for Disease Control and Prevention webpage on antibiotic/antimicrobial resistance includes information on educational campaigns and resources
The European Centre for Disease Control provides data about the prevalence of resistance in Europe through an interactive database
PMCID: PMC3191157  PMID: 22022233

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