Hakan Leblebicioglu

Device-Associated Nosocomial Infections in 55 Intensive Care Units of 8 Developing Countries

Context We know little about medical deviceassociated infections in developing countries. Contribution Prospective surveillance of 21069 patients who were hospitalized in 55 intensive care units in 46 hospitals in Central and South America, India, Morocco, and Turkey showed high rates (22.5 infections per 1000 intensive care unit days) of device-associated infections. Infections included ventilator-associated pneumonia (24.1 cases/1000 ventilator days), central venous catheterrelated bloodstream infections (12.5 cases/1000 catheter days), and catheter-associated urinary tract infections (8.9 cases/1000 catheter days). Eighty-four percent of Staphylococcus aureus infections were caused by methicillin-resistant strains, 51% of Enterobacteriaceae isolates were ceftriaxone-resistant, and 59% of Pseudomonas aeruginosa isolates were fluoroquinolone-resistant. Implications Medical deviceassociated infections pose major risks in developing countries. The Editors Surveillance of health careassociated infections, especially in high-risk hospital settings, such as the intensive care unit (ICU) (1, 2), has become an integral feature of infection control and quality assurance in all U.S. hospitals. The Centers for Disease Control and Prevention (CDC) Study of the Efficacy of Nosocomial Infection Control (SENIC) Project (3) showed that surveillance can help prevent health careassociated infections. Standards for institutional surveillance have been adopted in the United States (1), the United Kingdom (4), Australia (5), Canada (6), and Germany (7). A growing body of literature has shown that health careassociated infections are a major cause of patient illness and death in developed countries (8, 9). Device-associated infections, particularly ventilator-associated pneumonia (1012), central venous catheter (CVC)associated bloodstream infections (1315), and catheter-associated urinary tract infections (16, 17), pose the greatest threat to patient safety in the ICU (18). Surveillance of health careassociated infection has been standardized by the CDCs National Nosocomial Infection Surveillance (NNIS) System by providing simple unambiguous definitions, especially for device-associated infections (1921). Targeted surveillance and calculation of device-associated infection rates per 1000 device days allows benchmarking with similar other hospitals and detection of unique institutional problems that need redress. Most published studies of ICU-acquired infections have come from hospitals in industrialized western countries (1, 8, 1019, 22, 23). Relatively few data have been reported from developing countries (9, 2427), especially rates of device-associated infections by using standardized definitions. We report the initial findings of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2002 through December 2005. The consortium was established by Dr. Rosenthal in 1998 when selected hospitals in Latin America began collecting surveillance data on health careassociated infections for inclusion in a regional database. Consortium hospitals provide general medical and surgical inpatient services to adults and children who require short-term care. All data from the participating hospitals were collected by using standardized NNIS System protocols and definitions (1921). The consortium has initially focused on surveillance and prevention of device-associated infections in adult and pediatric ICUs and high-risk nurseries. Methods Setting Most current participating hospitals and ICUs joined the consortium since 2002 after hearing Dr. Rosenthal (the INICC chairman) speak in their country or after learning about the INICC from its Web site (www.inicc.org), but some hospitals were actively solicited. Study data were collected between 2002 and 2005 in 55 ICUs in 46 hospitals from 8 developing countries: Argentina, Brazil, Colombia, India, Mexico, Morocco, Peru, and Turkey. The consortium requires each member hospital to have an infection control team, comprising a physician and an infection control practitioner, and a microbiology laboratory that can isolate and identify aerobic pathogens from clinical cultures and perform in vitro susceptibility testing by using standardized methods (28). The person responsible for surveillance in each institution must have had at least 3 years of infection control experience (Table 1). In most of the hospitals, the team had access to electronic patient data. Table 1. Features of the International Nosocomial Infection Control Consortium Hospitals and Intensive Care Units* The institutional review board at each hospital approved the study protocol. Patient confidentiality is protected by coding the recorded information, with patient identities available only to the individual hospitals infection control team. Infection Control Practices at the Study Sites Hand hygiene adherence varies in the different countries and ICUs, ranging from 20% to 70% (2932). A recent study in all participating ICUs found a 50% overall rate of hand hygiene adherence (32), similar to that of recent studies in the United States and Europe (33). Use of sterile dressings on CVC insertion sites also ranges widely (29, 34, 35). Open infusion systems (rigid or semirigid containers that must admit air to empty) rather than closed systems (fully collapsible containers that do not require any external vent to empty the solution; the container residue after administration does not exceed 5% of the nominal volume) or combinations of open and closed systems are universally used to deliver intravenous fluids and medications in the study hospitals (35). Surveillance and Case Report Forms Each center established an augmented infection control program, with the initial major emphasis on active surveillance of health careassociated infections and process surveillance of hand hygiene adherence and invasive device care. During the study, we determined the rates of ventilator-associated pneumonia, CVC-associated bloodstream infection, and catheter-associated urinary tract infection monthly by using current CDC NNIS System definitions (1921). Designated surveillance forms were used for all patients in the study ICUs, both patients with and those without health careassociated infection. The following data were to be recorded daily on the forms for each patient: temperature and blood pressure, invasive devices, all cultures done, imaging studies, and antibiotic use. Previous studies have shown that fever, hypotension, cultures, and initiation of antimicrobial therapy are powerful markers for the presence of a health careassociated infection (36). A mean average severity of illness score was also recorded for each patient at ICU admission by using the CDC NNIS System criteria (19). Points were totaled, with 1 point for surgical patients who require routine postoperative observation only, 2 points for physiologically stable nonsurgical patients who require overnight observation, 3 points for patients who need continuous nursing care and monitoring, 4 points for physiologically unstable patients who require intensive nursing and medical care and need frequent reassessment and adjustment of therapy, and 5 points for physiologically unstable patients who are in a coma or in shock and require cardiopulmonary resuscitation or intensive medical and nursing care with frequent reassessment. If a patient was determined to have acquired a health careassociated infection, the date of onset, site of infection, infecting microorganisms, and antimicrobial susceptibilities were also recorded. Definitions Ventilator-Associated Pneumonia Ventilator-associated pneumonia is indicated in a mechanically ventilated patient with a chest radiograph that shows new or progressive infiltrates, consolidation, cavitation, or pleural effusion. The patient must also have at least 1 of the following criteria: new onset of purulent sputum or change in character of sputum; organism cultured from blood; or isolation of an etiologic agent from a specimen obtained by tracheal aspirate, bronchial brushing or bronchoalveolar lavage, or biopsy. Laboratory-Confirmed CVC-Associated Bloodstream Infection Central venous catheterassociated bloodstream infection is laboratory-confirmed when a patient with a CVC has a recognized pathogen that is isolated from 1 or more percutaneous blood cultures after 48 hours of vascular catheterization and is not related to an infection at another site. The patient also has at least 1 of the following signs or symptoms: fever (temperature 38C), chills, or hypotension. With skin commensals (for example, diphtheroids, Bacillus spp., Propionibacterium spp., coagulase-negative staphylococci, or micrococci), the organism is cultured from 2 or more blood cultures. Clinically Suspected CVC-Associated Bloodstream Infection Central venous catheterassociated bloodstream infection is clinically suspected when a patient with a CVC has at least 1 of the following clinical signs with no other identified cause: fever (temperature 38C), hypotension (systolic blood pressure 90 mm Hg), or oliguria (urine output 20 mL/h) with blood cultures not obtained or no organisms recovered from blood cultures, infections not apparent at another site, and antimicrobial therapy instituted by the physician. Catheter-Associated Urinary Tract Infection For the diagnosis of catheter-associated urinary tract infection, the patient must meet 1 of 2 criteria. The first criterion is when a patient with a urinary catheter has 1 or more of the following symptoms with no other recognized cause: fever (temperature 38C), urgency, or suprapubic tenderness when the urine culture is positive for 105 colony-forming units per mL or more, with no more than 2 microorganisms isolated. The second criterion is when a patient with a urinary catheter has at least 2 of the following criteria with no other recognized cause: positive dipstick analysis for leukocyte esterase or nitr

International Nosocomial Infection Control Consortium report, data summary for 2002-2007, issued January 2008

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from 2002 through 2007 in 98 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study, using Centers for Disease Control and Prevention (CDC) National Nosocomial Infections Surveillance System (NNIS) definitions for device-associated health care-associated infection, we collected prospective data from 43,114 patients hospitalized in the Consortiums hospital ICUs for an aggregate of 272,279 days. Although device utilization in the INICC ICUs was remarkably similar to that reported from US ICUs in the CDCs National Healthcare Safety Network, rates of device-associated nosocomial infection were markedly higher in the ICUs of the INICC hospitals: the pooled rate of central line-associated bloodstream infections (CLABs) in the INICC ICUs, 9.2 per 1000 CL-days, is nearly 3-fold higher than the 2.4-5.3 per 1000 CL-days reported from comparable US ICUs, and the overall rate of ventilator-associated pneumonia was also far higher, 19.5 vs 1.1-3.6 per 1000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 6.5 versus 3.4-5.2 per 1000 catheter-days. Most strikingly, the frequencies of resistance of Staphylococcus aureus isolates to methicillin (MRSA) (80.8% vs 48.1%), Enterobacter species to ceftriaxone (50.8% vs 17.8%), and Pseudomonas aeruginosa to fluoroquinolones (52.4% vs 29.1%) were also far higher in the Consortiums ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 14.3% (CLABs) to 27.5% (ventilator-associated pneumonia).

Impact of International Nosocomial Infection Control Consortium (INICC) Strategy on Central Line–Associated Bloodstream Infection Rates in the Intensive Care Units of 15 Developing Countries

BACKGROUND The International Nosocomial Infection Control Consortium (INICC) was established in 15 developing countries to reduce infection rates in resource-limited hospitals by focusing on education and feedback of outcome surveillance (infection rates) and process surveillance (adherence to infection control measures). We report a time-sequence analysis of the effectiveness of this approach in reducing rates of central line-associated bloodstream infection (CLABSI) and associated deaths in 86 intensive care units with a minimum of 6-month INICC membership. METHODS Pooled CLABSI rates during the first 3 months (baseline) were compared with rates at 6-month intervals during the first 24 months in 53,719 patients (190,905 central line-days). Process surveillance results at baseline were compared with intervention period data. RESULTS During the first 6 months, CLABSI incidence decreased by 33% (from 14.5 to 9.7 CLABSIs per 1,000 central line-days). Over the first 24 months there was a cumulative reduction from baseline of 54% (from 16.0 to 7.4 CLABSIs per 1,000 central line-days; relative risk, 0.46 [95% confidence interval, 0.33-0.63]; P < .001). The number of deaths in patients with CLABSI decreased by 58%. During the intervention period, hand hygiene adherence improved from 50% to 60% (P < .001); the percentage of intensive care units that used maximal sterile barriers at insertion increased from 45% to 85% (P < .001), that adopted chlorhexidine for antisepsis increased from 7% to 27% (P < .001), and that sought to remove unneeded catheters increased from 37% to 83% (P < .001); and the duration of central line placement decreased from 4.1 to 3.5 days (P < .001). CONCLUSIONS Education, performance feedback, and outcome and process surveillance of CLABSI rates significantly improved infection control adherence, reducing the CLABSI incidence by 54% and the number of CLABSI-associated deaths by 58% in INICC hospitals during the first 2 years.

Crimean–Congo haemorrhagic fever in Eurasia

Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne infectious disease characterized by fever, malaise, headache, nausea, vomiting, diarrhoea, sore throat, muscle aches, haemorrhage and thrombocytopenia. It is a challenge for the population of endemic rural areas, and for healthcare workers, and carries a considerable mortality. The disease is widely distributed in Africa, Europe and Asia, and has become a serious threat to public health in Eurasia. The intention of this review is to summarize the current status of CCHF in Eurasia.

Efficacy of oral ribavirin treatment in Crimean-Congo haemorrhagic fever: a quasi-experimental study from Turkey.

OBJECTIVE The aim of this study was to evaluate the efficacy of oral ribavirin treatment in patients with Crimean-Congo haemorrhagic fever (CCHF). METHODS In 2004, all patients diagnosed with CCHF were treated with oral ribavirin, however in 2003 none of the CCHF patients had been given treatment due to lack of confirmatory diagnostic information at that time in Turkey. In this study, patients treated with ribavirin in 2004 (n=126) were compared with ribavirin-untreated CCHF patients (n=92) in 2003. Patients only with a definitive diagnosis of CCHF (clinical symptoms plus the presence of specific IgM antibodies against CCHF virus and presence of viral antigen) were included in this study. RESULTS There was no difference in the case-fatality rate between treated and untreated patients (7.1% vs. 11.9%; P>0.05). A Cox Proportional Hazards regression analysis revealed that altered sensorium and prolonged international normalized ratio were independent predictors of mortality. CONCLUSION Our results showed that oral ribavirin treatment did not improve the survival rate in CCHF patients. Ribavirin and supportive care are the only available choices for treatment of CCHF patients, but to ascertain the efficacy of ribavirin, more laboratory and observational studies are necessary and ultimately, to elucidate these conflicting results and evaluate the efficacy undoubtedly, a multicenter randomised controlled trial will be needed.

Ribavirin for patients with Crimean–Congo haemorrhagic fever: a systematic review and meta-analysis

BACKGROUND Crimean-Congo haemorrhagic fever (CCHF) is a potentially fatal tick-borne infection. The virus is widely distributed around the world and reports of sporadic cases and outbreaks have recently increased significantly. Some authors have proposed that ribavirin improves survival in CCHF and this view appears to be widely accepted. METHODS We evaluated the efficacy of ribavirin in reducing mortality by conducting a systematic review and meta-analysis. We included randomized controlled trials and observational studies that compared the outcomes of CCHF patients who were treated with ribavirin with those of patients that were not treated. The main endpoint we assessed was survival. We also evaluated secondary endpoints, i.e. adverse events, length of stay in the hospital, time taken for laboratory values to return to normal and requirement for blood products. A pooled estimate of the relative risks for survival from each study was obtained by using random effects models. RESULTS One randomized controlled trial and seven observational studies met our inclusion criteria. Most observational studies suffered from different types of bias due to inappropriate selection of controls. Compilation of data from all included studies showed that ribavirin did not improve survival in CCHF (relative risk 1.06, 95% confidence interval 0.97-1.16). Analysis of secondary endpoints did not suggest a clinically significant beneficial effect either. CONCLUSIONS Our systematic review and meta-analysis revealed that the available data in the literature are inadequate to support a claim of efficacy of ribavirin in CCHF. We believe a real uncertainty exists over the benefit of ribavirin in the treatment of CCHF, which necessitates the urgent conduct of a randomized placebo-controlled trial.

Prevalence of nosocomial infections at intensive care units in Turkey: A multicentre 1-day point prevalence study

In order to determine the prevalence of intensive care unit (ICU)-acquired infection at ICUs in Turkey and to identify associated risk factors, predominant infecting organisms and mortality rates, a 1-d point prevalence study was carried out on 19 September 2001. A total of 56 ICUs from 22 university and teaching hospitals participated and a total of 236 completed case report forms were accepted for analyses. A total of 115 patients (48.7%) had 1 or more ICU- related nosocomial infections on the study d. Pneumonia and lower respiratory tract infection (28.0%), laboratory confirmed blood stream infection (23.3%) and urinary tract infection (15.7%) were the most frequent types. Endotracheal tube, urinary catheter, multi-trauma on admission, stress ulcer prophylaxis, nasogastric feeding and mechanical ventilation were risk factors. The most frequently reported isolates were Pseudomonas aeruginosa (20.8%), Staphylococcus aureus (18.2%), Acinetobacter spp. (18.2%) and Klebsiella spp. (16.1%). Of the patients, 72.9% were receiving antimicrobials on the study d for treatment or prophylaxis. Most frequently administered antimicrobials were aminoglycosides (37.2%), carbapenems (31.4%), glycopeptides (23.3%), cephalosporins (18.0%) and antifungals (5.8%). According to a 4-week follow-up, 70 (29.7%) patients died, 22 (9.3%) of whom died from ICU related infections. In conclusion this study showed that ICU related infections are common and often associated with resistant microorganisms. The results provide epidemiological information that will help to implement infection control policies in ICUs.

Surgical Site Infections, International Nosocomial Infection Control Consortium (INICC) Report, Data Summary of 30 Countries, 2005–2010

OBJECTIVE  To report the results of a surveillance study on surgical site infections (SSIs) conducted by the International Nosocomial Infection Control Consortium (INICC). DESIGN  Cohort prospective multinational multicenter surveillance study. SETTING  Eighty-two hospitals of 66 cities in 30 countries (Argentina, Brazil, Colombia, Cuba, Dominican Republic, Egypt, Greece, India, Kosovo, Lebanon, Lithuania, Macedonia, Malaysia, Mexico, Morocco, Pakistan, Panama, Peru, Philippines, Poland, Salvador, Saudi Arabia, Serbia, Singapore, Slovakia, Sudan, Thailand, Turkey, Uruguay, and Vietnam) from 4 continents (America, Asia, Africa, and Europe). PATIENTS  Patients undergoing surgical procedures (SPs) from January 2005 to December 2010. METHODS  Data were gathered and recorded from patients hospitalized in INICC member hospitals by using the methods and definitions of the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) for SSI. SPs were classified into 31 types according to International Classification of Diseases, Ninth Revision, criteria. RESULTS  We gathered data from 7,523 SSIs associated with 260,973 SPs. SSI rates were significantly higher for most SPs in INICC hospitals compared with CDC-NHSN data, including the rates of SSI after hip prosthesis (2.6% vs. 1.3%; relative risk [RR], 2.06 [95% confidence interval (CI), 1.8-2.4]; P < .001), coronary bypass with chest and donor incision (4.5% vs. 2.9%; RR, 1.52 [95% CI, 1.4-1.6]; [P < .001); abdominal hysterectomy (2.7% vs. 1.6%; RR, 1.66 [95% CI, 1.4-2.0]; P < .001); exploratory abdominal surgery (4.1% vs. 2.0%; RR, 2.05 [95% CI, 1.6-2.6]; P < .001); ventricular shunt, 12.9% vs. 5.6% (RR, 2.3 [95% CI, 1.9-2.6]; P < .001, and others. CONCLUSIONS  SSI rates were higher for most SPs in INICC hospitals compared with CDC-NHSN data.

Pathogenesis of Crimean-Congo Hemorrhagic Fever

Although Crimean-Congo hemorrhagic fever (CCHF) is a widespread tick-borne disease, little is known about its pathogenesis. The interaction of the virus with host cells is most likely responsible for the pathogenesis of CCHF. The main contributors are endothelial cells (ECs) and immune cells. There are 2 theories underlying the CCHF pathogenesis: One is that the virus interacts with the ECs directly and the other that it interacts indirectly via immune cells with subsequent release of soluble mediators. ECs are activated upon infection by the upregulation of soluble molecules and proinflammatory cytokines. Probably, in severe cases, deregulation and excessive release of the cytokines accompanied by endothelial activation have toxic effects, leading to increased vascular permeability, vasodilatation, and subsequently hypotension, multiple organ failure, shock, and death. Studies indicate that CCHF virus (CCHFV) also can impair the innate immune system and cause a delay in adaptive immune response, which is critical for the clearance of CCHFV. The virus has many different ways to block the immune response, leading to uncontrolled viral replication followed by systemic spread of the virus throughout the body. Partial activation of dendritic cells and macrophages, delayed induction of interferons, weak antibody response, apoptosis of lymphocytes, and hemophagocytosis are some of these tactics. However, there are many points waiting for clarification about the pathogenesis of CCHF. Although the high risk of contagiousness limits research, we need more studies to understand the CCHF pathogenesis better. Here we review the main characteristics of the pathogenesis of CCHF.

Case Management and Supportive Treatment for Patients with Crimean-Congo Hemorrhagic Fever

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne infection which has been increasing in Turkey and European countries since the year 2000. The disease is particularly endemic in the Middle East and in some African countries. It is also seen in European countries as a travel infection. Patients with confirmed diagnosis are usually hospitalized for monitoring, while patients with good overall condition may be monitored on an outpatient basis. Hospitals that manage CCHF should have easy access to a blood bank, and tertiary care hospitals must have a well-equipped intensive care unit. Strict blood and body fluid control precautions should be started on admission to limit CCHF exposure. The follow-up period for each patient is determined based on individual clinical status and laboratory values. Since there is no specific antiviral treatment for CCHF, supportive treatment is essential. This review highlights some of the major features of case monitoring and supportive treatment in CCHF.