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1.  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
2.  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
3.  Prevalence of antibiotic resistance in multi-drug resistant coagulase-negative staphylococci isolated from invasive infection in very low birth weight neonates in two Polish NICUs 
Multi-drug resistant coagulaso-negative staphylococci (CNS) have become an increasing problem in nosocomial infections connected with the presence of medical devices. The paper aimed to analyze the prevalence of antibiotic resistance in CNS isolated from invasive infection in very low birth weight (VLBW) neonates.
Continuous prospective target surveillance of infections was conducted in 2009 at two Polish NICUs that participated in the Polish Neonatology Surveillance Network (PNSN). The study covered 386 neonates with VLBW (≤1500 g), among which 262 cases of invasive infection were detected with predominance of CNS (123; 47%). Altogether, 100 CNS strains were analyzed. The resistance phenotypes were determined according to EUCAST. Resistance genes: mecA, ermA, ermB, ermC, msrA, aac(6')/aph(2''), ant(4')-Ia and aph(3')-IIIa were detected using multiplex PCR.
The most common species was S. epidermidis (63%), then S. haemolyticus (28%) and other CNS (9%). Among S. epidermidis, 98% of isolates were resistant to methicillin, 90% to erythromycin, 39% to clindamycin, 95% to gentamicin, 60% to amikacin, 36% to ofloxacin, 2% to tigecycline, 3% to linezolid and 13% to teicoplanin. Among S. haemolyticus isolates, 100% were resistant to methicillin, erythromycin and gentamicin, 18% to clindamycin, 50% to amikacin, 86% to ofloxacin, 14% to tigecycline and 4% to teicoplanin. No resistance to linezolid was detected for S. haemolyticus isolates. Moreover, all isolates of S. epidermidis and S. haemolyticus were susceptible to vancomycin. The mecA gene was detected in 98% of S. epidermidis isolates and all of S. haemolyticus ones. Among macrolide resistance isolates, the ermC was most common in S. epidermidis (60%) while msrA was prevalent in S. haemolyticus (93%). The ermC gene was indicated in all isolates with cMLSB, whereas mrsA was found in isolates with MSB phenotype. Of the aminoglycoside resistance genes, aac(6')/aph(2'') were present alone in 83% of S. epidermidis, whereas aac(6')/aph(2'') with aph(3')-IIIa were predominant in 84% of S. haemolyticus.
Knowing the epidemiology and antibiotic resistance of CNS isolated from invasive infection in VLBW neonates is a key step in developing targeted prevention strategies and reducing antibiotic consumption.
PMCID: PMC3898809  PMID: 24359473
Multi-drug resistant coagulase-negative staphylococci; Resistance genes; Very-low-birth-weight neonates; Nosocomial infections
4.  Feeding back surveillance data to prevent hospital-acquired infections. 
Emerging Infectious Diseases  2001;7(2):295-298.
We describe the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance system. Elements of the system critical for successful reduction of nosocomial infection rates include voluntary participation and confidentiality; standard definitions and protocols; identification of populations at high risk; site-specific, risk- adjusted infection rates comparable across institutions; adequate numbers of trained infection control professionals; dissemination of data to health-care providers; and a link between monitored rates and prevention efforts.
PMCID: PMC2631724  PMID: 11294727
5.  Epidemiology and Diagnosis of Hospital-Acquired Conjunctivitis Among Neonatal Intensive Care Unit Patients 
Few recent reports describe the epidemiology and risk factors for health care-associated conjunctivitis among neonatal intensive care unit (NICU) patients in developed countries. Reporting may be inaccurate in this population given that the National Nosocomial Infection Surveillance System (NNIS) definition is largely dependent on a positive culture, whereas clinical practice often consists of empiric treatment.
We describe the epidemiology of conjunctivitis among neonates in 2 level III–IV NICUs and compare the NNIS definition with our study definition: eye drainage and empiric treatment with or without a culture.
Patient demographics, clinical, device usage and conjunctivitis data collected prospectively from March 2001 through January 2003 were analyzed.
Conjunctivitis occurred in 5% (n = 154/2935) of infants, of whom 51% (n =79) were in NICU 1 and 49% (n =75) in NICU 2. Predominant pathogens included coagulase-negative staphylococci (25%), Staphylococcus aureus (19%) and Klebsiella spp. (10%). Significant predictors of conjunctivitis included low birth weight, use of ventilator or nasal cannula continuous positive airway pressure and study year. Ophthalmologic examination was an additional predictor of infection in NICU 1. Eye examination data were unavailable for NICU 2. Only 62% of cases that met the study definition for conjunctivitis met the NNIS definition, because many infants received empiric treatment.
Clinical conjunctivitis was associated with low birth weight and patient care factors that could lead to contamination of the eye with respiratory tract secretions. The NNIS definition failed to detect 38% of clinical infections. Consideration should be given to revising the definition of conjunctivitis for the NICU population.
PMCID: PMC2045635  PMID: 15998997
conjunctivitis; neonatal intensive care unit; low birth weight; premature infants
6.  Development of a Reference Information Model and Knowledgebase for Electronic Bloodstream Infection Detection 
The most prevalent hospital-acquired infections in the United States are bloodstream infections (BSIs) associated with the presence of a central venous catheter. There is currently a movement, including national organizations such as the Centers for Medicare and Medicaid Services as well as consumer, quality improvement and patient safety groups, encouraging the standardization of reporting and aggregation of such nosocomial infection data to increase and improve reporting, and enable rate comparisons among healthcare institutions. Domain modeling is a well-known method for designing interoperable processes that take advantage of existing data and legacy systems. We have combined such a model-driven design approach with the use of partitioned clinical and business logic knowledgebases in order to employ a previously validated electronic BSI surveillance algorithm in the context of a multi-center study.
PMCID: PMC2656042  PMID: 18999213
7.  Linkage, Evaluation and Analysis of National Electronic Healthcare Data: Application to Providing Enhanced Blood-Stream Infection Surveillance in Paediatric Intensive Care 
PLoS ONE  2013;8(12):e85278.
Linkage of risk-factor data for blood-stream infection (BSI) in paediatric intensive care (PICU) with bacteraemia surveillance data to monitor risk-adjusted infection rates in PICU is complicated by a lack of unique identifiers and under-ascertainment in the national surveillance system. We linked, evaluated and performed preliminary analyses on these data to provide a practical guide on the steps required to handle linkage of such complex data sources.
Data on PICU admissions in England and Wales for 2003-2010 were extracted from the Paediatric Intensive Care Audit Network. Records of all positive isolates from blood cultures taken for children <16 years and captured by the national voluntary laboratory surveillance system for 2003-2010 were extracted from the Public Health England database, LabBase2. “Gold-standard” datasets with unique identifiers were obtained directly from three laboratories, containing microbiology reports that were eligible for submission to LabBase2 (defined as “clinically significant” by laboratory microbiologists). Reports in the gold-standard datasets were compared to those in LabBase2 to estimate ascertainment in LabBase2. Linkage evaluated by comparing results from two classification methods (highest-weight classification of match weights and prior-informed imputation using match probabilities) with linked records in the gold-standard data. BSI rate was estimated as the proportion of admissions associated with at least one BSI.
Reporting gaps were identified in 548/2596 lab-months of LabBase2. Ascertainment of clinically significant BSI in the remaining months was approximately 80-95%. Prior-informed imputation provided the least biased estimate of BSI rate (5.8% of admissions). Adjusting for ascertainment, the estimated BSI rate was 6.1-7.3%.
Linkage of PICU admission data with national BSI surveillance provides the opportunity for enhanced surveillance but analyses based on these data need to take account of biases due to ascertainment and linkage error. This study provides a generalisable guide for linkage, evaluation and analysis of complex electronic healthcare data.
PMCID: PMC3869925  PMID: 24376874
8.  Concordance of Gastrointestinal Tract Colonization and Subsequent Bloodstream Infections with Gram-negative Bacilli in Very Low Birthweight Infants in the Neonatal Intensive Care Unit 
Gram-negative bacilli (GNB) cause as many as 20% of episodes of late-onset sepsis among very low birth weight (VLBW, birth weight < or =1500 g) infants in the neonatal intensive care unit. As the gastrointestinal (GI) tract can serve as a reservoir for GNB, we hypothesized that VLBW infants with prior GI tract colonization with gentamicin-susceptible GNB who developed bloodstream infections (BSI) would do so with gentamicin-susceptible GNB.
A prospective cohort study of VLBW infants was performed in 2 level III neonatal intensive care units from September 2004 to October 2007. GI tract surveillance cultures were obtained weekly. Risk factors for GNB BSI and for GI tract colonization with GNB were assessed.
Fifty-one (7.3%) of 698 subjects experienced 59 GNB BSIs of which 34 occurred by 6 weeks of life and 625 (90%) of 698 subjects were colonized with GNB. Overall, 25% of BSI and 16% of GI tract isolates were nonsusceptible to gentamicin and colonization with the same species and same gentamicin susceptibility profile preceded 98% of GNB BSIs. Vaginal delivery, birth weight < or =750 g, GI tract pathology, increased use of central venous catheters, use of vancomycin, mechanical ventilation, and H2 blockers/proton pump inhibitors were associated with GNB BSI. Vaginal delivery, birth weight >1000 g, and treatment with carbapenem agents were associated with GNB colonization.
These data support the use of empiric gentamicin to treat late-onset sepsis in infants colonized with gentamicin-susceptible GNB. Targeted GI tract surveillance cultures of infants with specific risk factors during weeks 2 to 6 of life could be used to guide empiric therapy for late-onset sepsis.
PMCID: PMC2949271  PMID: 20539251
NICU; neonatal infections; gram-negative bloodstream infection; gastrointestinal tract; colonization; late-onset sepsis
9.  Characteristics of HIV seroprevalence of visitors to public health centers under the national HIV surveillance system in Korea: cross sectional study 
BMC Public Health  2009;9:123.
In Korea, the cumulative number of HIV-infected individuals was smaller than those of other countries. Mandatory HIV tests, dominating method until 1990's, have been gradually changed to voluntary HIV tests. We investigated HIV seroprevalence status and its characteristics of visitors to Public Health Centers (PHCs), which conducted both mandatory test and voluntary test under the national HIV/STI surveillance program.
We used HIV-testing data from 246 PHCs in 2005 through the Health Care Information System. The number of test taker was calculated using the code distinguished by the residential identification number. The subjects were classified into four groups by reason for testing; General group, HIV infection suspected group (HIV ISG), HIV test recommended group (HIV TRG), and sexually transmitted infection (STI) risk group.
People living with HIV/AIDS were 149 (124 male and 25 female) among 280,456 individuals tested at PHCs. HIV seroprevalence was 5.3 per 10,000 individuals. Overall, the male revealed significantly higher seroprevalence than the female (adjusted Odds Ratio (adj. OR): 6.2; CI 3.8–10.2). Individuals aged 30–39 years (adj. OR: 2.6; CI 1.7–4.0), and 40–49 years (adj. OR: 3.8; CI 2.4–6.0) had higher seroprevalence than 20–29 years. Seroprevalence of HIV ISG (voluntary test takers and cases referred by doctors) was significantly higher than those of others. Foreigners showed higher seroprevalence than native Koreans (adj. OR: 3.8; CI 2.2–6.4). HIV ISG (adj. OR: 4.9; CI 3.2–7.5), and HIV TRG (adj. OR: 2.6; CI 1.3–5.4) had higher seroprevalence than General group.
A question on the efficiency of current mandatory test is raised because the seroprevalence of mandatory test takers was low. However, HIV ISG included voluntary test takers was high in our result. Therefore, we suggest that Korea needs to develop a method encouraging more people to take voluntary tests at PHCs, also to expand the anonymous testing centers and Voluntary Counselling and Testing Program (VCT) for general population to easily access to HIV testing.
PMCID: PMC2689198  PMID: 19416524
10.  The investment case for preventing NICU-associated infections 
American journal of perinatology  2012;30(3):179-184.
Nosocomial (hospital-associated or NICU-associated) infections occur in as many as 10–36% of very low birth weight infants cared for in newborn intensive care units (NICU).
To determine the potentially avoidable, incremental costs of care associated with NICU-associated bloodstream infections.
Study Design
This is a retrospective study that included all NICU admissions of infants 401–1500 grams birth weight in the greater Cincinnati region from January 1, 2005 through December 31, 2007. Non-physician costs of care were compared between infants who developed at least one bacterial bloodstream infection prior to NICU discharge or death and infants who did not. Costs were adjusted for clinical and demographic characteristics that are present in the first three days of life and are known associates of infection.
Among 900 study infants with no congenital anomaly and no major surgery, 82 (9.1%) developed at least one bacterial bloodstream infection. On average, the cost of NICU care was $16,800 greater per infant who experienced NICU-associated bloodstream infection.
Potentially avoidable costs of care associated with bloodstream infection can be used to justify investments in the reliable implementation of evidence-based interventions designed to prevent these infections.
PMCID: PMC3789586  PMID: 22836823
quality improvement; investment case; nosocomial infection
11.  Incidence and implications of unrecognized viral respiratory tract infections in premature infants during their birth hospitalization: a prospective surveillance study in two neonatal intensive care units 
The Journal of pediatrics  2012;161(5):814-818.
We sought to determine the frequency and effects of nosocomial respiratory viral infections (RVIs) in premature neonates, including those who may be asymptomatic.
Study Design
We performed a year-long surveillance for RVIs in infants <33 weeks gestational age admitted to two Syracuse neonatal intensive care units (NICUs). Infants were enrolled within 3 days of NICU admission and were sampled for RVIs until discharge using a multiplex PCR assay capable of detecting 17 different respiratory viruses or subtypes.
26 of 50 prematurely born infants (52%) tested positive for a respiratory virus at least once during their birth hospitalization. Testing positive for a respiratory virus was significantly associated with longer length of stay (70 days vs. 35 days, p = 0.002) and prolonged ventilatory support (51 vs. 13 days, p = 0.002). Infants who tested positive for a respiratory virus during their birth hospitalization had more than twice the rate of developing bronchopulmonary dysplasia (BPD; p < 0.05).
Nosocomial RVIs were frequent in our study population, despite the absence of clinical indicators of illness. Length of hospital stay was significantly longer and a diagnosis of BPD was more common in those premature infants who had respiratory viruses detected.
PMCID: PMC3731035  PMID: 22694859
neonatal infection; respiratory viral infection; premature newborn
12.  Nosocomial Bloodstream Infections in Brazilian Pediatric Patients: Microbiology, Epidemiology, and Clinical Features 
PLoS ONE  2013;8(7):e68144.
Nosocomial bloodstream infections (nBSIs) are an important cause of morbidity and mortality and are the most frequent type of nosocomial infection in pediatric patients.
We identified the predominant pathogens and antimicrobial susceptibilities of nosocomial bloodstream isolates in pediatric patients (≤16 years of age) in the Brazilian Prospective Surveillance for nBSIs at 16 hospitals from 12 June 2007 to 31 March 2010 (Br SCOPE project).
In our study a total of 2,563 cases of nBSI were reported by hospitals participating in the Br SCOPE project. Among these, 342 clinically significant episodes of BSI were identified in pediatric patients (≤16 years of age). Ninety-six percent of BSIs were monomicrobial. Gram-negative organisms caused 49.0% of these BSIs, Gram-positive organisms caused 42.6%, and fungi caused 8.4%. The most common pathogens were Coagulase-negative staphylococci (CoNS) (21.3%), Klebsiella spp. (15.7%), Staphylococcus aureus (10.6%), and Acinetobacter spp. (9.2%). The crude mortality was 21.6% (74 of 342). Forty-five percent of nBSIs occurred in a pediatric or neonatal intensive-care unit (ICU). The most frequent underlying conditions were malignancy, in 95 patients (27.8%). Among the potential factors predisposing patients to BSI, central venous catheters were the most frequent (66.4%). Methicillin resistance was detected in 37 S. aureus isolates (27.1%). Of the Klebsiella spp. isolates, 43.2% were resistant to ceftriaxone. Of the Acinetobacter spp. and Pseudomonas aeruginosa isolates, 42.9% and 21.4%, respectively, were resistant to imipenem.
In our multicenter study, we found a high mortality and a large proportion of gram-negative bacilli with elevated levels of resistance in pediatric patients.
PMCID: PMC3701648  PMID: 23861860
13.  Invasive fungal infection in very low birthweight infants: national prospective surveillance study 
To describe the epidemiology of invasive fungal infection in very low birthweight (VLBW: <1500 g) infants in the United Kingdom.
National prospective surveillance study between February 2003 and February 2004 using the British Paediatric Surveillance Unit reporting system reconciled with cases identified through routine laboratory reporting to the Health Protection Agency (England, Wales, and Northern Ireland), the Scottish Centre for Infection and Environmental Health, and the UK Mycology Reference Laboratory.
Ninety four confirmed cases of invasive fungal infection were identified during the surveillance period giving an incidence of estimated annual incidence of 10.0 (95% confidence interval (CI) 8.0 to 12.0) cases per 1000 VLBW live births. Eighty one (86%) of the infants were of extremely low birth weight (ELBW: <1000 g), incidence 21.1 (95% CI 16.5 to 25.7) per 1000 ELBW live births. Candida species, predominantly C albicans and C parapsilosis, were isolated in 93% of cases. Most organisms were isolated from the bloodstream and urinary tract. Death occurred in 41% of the infected infants before 37 weeks postconceptional age.
The incidence of invasive fungal infection in VLBW and ELBW infants in the United Kingdom is lower than reported in previous studies from tertiary centres in North America and elsewhere. The associated late neonatal and post‐neonatal death rates are substantially higher than expected in infants without invasive fungal infection. These data may inform decisions about the evaluation and use of antifungal infection control strategies.
PMCID: PMC2672702  PMID: 16332924
very low birth weight; candida; surveillance; fungal infection
14.  Molecular Epidemiology of Staphylococcus epidermidis in a Neonatal Intensive Care Unit over a Three-Year Period 
Journal of Clinical Microbiology  2000;38(5):1740-1746.
Coagulase-negative staphylococci, especially Staphylococcus epidermidis, are increasingly important nosocomial pathogens, particularly in critically ill neonates. A 3-year prospective surveillance of nosocomial infections in a neonatal intensive care unit (NICU) was performed by traditional epidemiologic methods as well as molecular typing of microorganisms. The aims of the study were (i) to quantify the impact of S. epidermidis on NICU-acquired infections, (ii) to establish if these infections are caused by endemic clones or by incidentally occurring bacterial strains of this ubiquitous species, (iii) to evaluate the use of different methods for the epidemiologic typing of the isolates, and (iv) to characterize the occurrence and the spread of staphylococci with decreased glycopeptide susceptibility. Results confirmed that S. epidermidis is one of the leading causes of NICU-acquired infections and that the reduced glycopeptide susceptibility, if investigated by appropriate detection methods such as population analysis, is more common than is currently realized. Typing of isolates, which can be performed effectively through molecular techniques such as pulsed-field gel electrophoresis but not through antibiograms, showed that many of these infections are due to clonal dissemination and, thus, are potentially preventable by strict adherence to recommended infection control practices and the implementation of programs aimed toward the reduction of the unnecessary use of antibiotics. These strategies are also likely to have a significant impact on the frequency of the reduced susceptibility of staphylococci to glycopeptides, since this phenomenon appears to be determined either by more resistant clones transmitted from patient to patient or, to a lesser extent, by strains that become more resistant as a result of antibiotic pressure.
PMCID: PMC86575  PMID: 10790091
15.  Nosocomial infection in small for gestational age newborns with birth weight <1500 g: a multicentre analysis 
To investigate whether preterm newborns who are small for gestational age are at increased risk of nosocomial infections and necrotising enterocolitis.
Design, setting and subjects
The German national surveillance system for nosocomial infection in very low birthweight infants uses the US Centers for Disease Control and Prevention criteria. 2918 newborns (24–28 weeks), born between 2000 and 2004, were selected after application of predefined inclusion criteria to ensure similar proportions of small and appropriate weight for gestational age newborns across gestational age groups.
Main outcome measures
The outcome criterion was at least one episode of nosocomial sepsis, pneumonia or necrotising enterocolitis. Adjusted odds ratios and corresponding 95% CIs were calculated based on general estimating equation models.
The study population consisted of 13% (n = 392) small and 87% (n = 2526) appropriate weight for gestational age infants. 33% (n = 950) of the infants experienced at least one episode of sepsis: 42% (n = 163) of small and 31% (n = 787) of appropriate weight for gestational age newborns (adjusted OR 1.41, 95% CI 1.05 to 1.89). Pneumonia was diagnosed in 6% (n = 171) of infants: 8.4% (n = 33) of small and 5.5% (n = 138) of appropriate weight for gestational age newborns (adjusted OR 1.57, 95% CI 1.19 to 5.57). Necrotising enterocolitis was documented in 5.2% (n = 152) of infants: 7.1% (n = 28) of small and 4.9% of (n = 124) appropriate weight for gestational age newborns (adjusted OR 1.20, 95% confidence interval 0.75 to 1.94).
Growth‐retarded preterm infants seem to be at increased risk of nosocomial infection, irrespective of the responsible pathogen. Future immunological research should elucidate potential causal associations.
PMCID: PMC2675389  PMID: 17460021
16.  Emergence of Fluconazole Resistance in a Candida parapsilosis Strain That Caused Infections in a Neonatal Intensive Care Unit 
Journal of Clinical Microbiology  2005;43(6):2729-2735.
Candida parapsilosis is an increasing cause of bloodstream infections (BSIs) in neonatal intensive care units (NICUs). It has been a persistent problem in the NICU of Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland, since 1987. Fluconazole prophylaxis has been used to control the problem. The number of new infections has, however, increased markedly since September 2000. We assessed fluconazole consumption and occurrence of all Candida species in the NICU from 1991 to 2002. C. parapsilosis bloodstream isolates obtained in the NICU from 1990 to 2002 (n = 26) were genotyped and their fluconazole susceptibility was defined. A low rate of C. parapsilosis BSIs was correlated with high rates of consumption of fluconazole. No emergence of Candida species with primary resistance to fluconazole was detected. However, genotyping with a complex DNA fingerprinting probe revealed that a single strain of C. parapsilosis with decreasing susceptibility to fluconazole was responsible for cross-infections that caused BSIs in the NICU over a 12-year period. The emergence of fluconazole resistance in that strain was observed after more than 10 years of fluconazole prophylaxis.
PMCID: PMC1151957  PMID: 15956390
17.  Incidence of Bronchopulmonary Dysplasia in Korea 
Journal of Korean Medical Science  2012;27(8):914-921.
A nationwide survey was conducted to determine the incidence of bronchopulmonary dysplasia (BPD) in Korea and the intercenter differences in survival and BPD rates among preterm infants. Questionnaires were sent to all registered neonatal intensive care units (NICUs). The questionnaires inquired about the survival and BPD rates of very low birth weight (VLBW, < 1,500 g) infants who had been admitted to each NICU from 2007 to 2008. BPD was defined as requiring oxygen at 36 weeks' postmenstrual age. Almost all level III NICUs replied. During the study period, 3,841 VLBW infants were born in the NICUs that responded to the survey. The survival rate was 81% and the BPD rate was 18%. Combined outcome of BPD or death rate was 37%. The BPD rate and combined outcome of BPD or death rate varied considerably from 5% to 50% and 11% to 73%, respectively across the centers. There was no significant correlation between the survival rate and the BPD rate across the centers. In conclusion, the incidence of BPD among VLBW infants in Korea during the study period was 18%, and a considerable intercenter difference in BPD rates was noted.
PMCID: PMC3410240  PMID: 22876059
Bronchopulmonary Dysplasia; Epidemiology; Infant, Very Low Birth Weight
18.  Early and Late Onset Sepsis in Very-Low-Birth-Weight Infants from a Large Group of Neonatal Intensive Care Units 
Early human development  2012;88(Suppl 2):S69-S74.
Very-low-birth-weight (VLBW, <1500 g birth weight) infants are at high risk for both early- and late-onset sepsis. Prior studies have observed a predominance of gram-negative organisms as a cause of early-onset sepsis and gram-positive organisms as a cause of late-onset sepsis. These reports are limited to large, academic neonatal intensive care units (NICUs) and may not reflect findings in other units. The purpose of this study was to determine the risk factors for sepsis, the causative organisms, and mortality following infection in a large and diverse sample of NICUs.
We analyzed the results of all cultures obtained from VLBW infants admitted to 313 NICUs from 1997 to 2010.
Over 108,000 VLBW infants were admitted during the study period. Early-onset sepsis occurred in 1032 infants, and late-onset sepsis occurred in 12,204 infants. Gram-negative organisms were the most commonly isolated pathogens in early-onset sepsis, and gram-positive organisms were most commonly isolated in late-onset sepsis. Early- and late-onset sepsis were associated with increased risk of death controlling for other confounders (odds ratio 1.45 [95% confidence interval 1.21, 1.73], and OR 1.30 [95% CI 1.21, 1.40], respectively).
This is the largest report of sepsis in VLBW infants to date. Incidence for early-onset sepsis and late-onset sepsis has changed little over this 14-year period, and overall mortality in VLBW infants with early- and late-onset sepsis is higher than in infants with negative cultures.
PMCID: PMC3513766  PMID: 22633519
early-onset sepsis; late-onset sepsis; very-low-birth-weight infants
19.  Nosocomial infections in burn patients: etiology, antimicrobial resistance, means to control 
The aim of our study was to determine the etiology of nosocomial infections, their changes over a period of five years (2007-2011), and the measures for control of infections and antimicrobial resistance in the Burns Clinic of the N.I. Pirogov University Multi-Profile Hospital for Active Treatment and Emergency Medicine, Sofia, Bulgaria. The medical records for all the patients and the database of the “Clinical Microbiology and Surveillance of Infections” National Information System were reviewed and analyzed to identify the microbial pathogens isolated in our burns Clinic. The three most frequent nosocomial pathogens were S. aureus, A. baumannii and P. aeruginosa. In order to control effectively nosocomial infections, a system of anti-infective and anti- microbial resistance measures has been developed and routinely implemented in our Clinic since 2008. Since 2009, thanks to this system, there has been a significant decrease in the rates of multi-resistant Staphylococcus aureus strains. Although at present the incidence of the nosocomial infections in our burns clinic is lower than in neighboring countries, several important infection control issues still need to be solved. We mainly rely on updating and strengthening the existing anti-infective system in order to control the spread of multi-drug resistant organisms, such as A. baumannii, extended spectrum beta-lactamase-producing Enterobacteriaceae, and carbapenem-resistant P. aeruginosa.
PMCID: PMC3741010  PMID: 23966892
nosocomial infection; burns; multi-drug-resistant organisms
20.  Risk factors for late-onset health care-associated bloodstream infections in patients in neonatal intensive care units 
There are few data comparing risk factors for catheter-related (CR) versus non-CR bloodstream infection (BSI) or for BSI caused by gram-positive versus gram-negative organisms. The aims of this study were to compare risk factors for CR versus non-CR BSI and to compare risk factors for BSI associated with gram-negative versus gram-positive organisms among infants hospitalized in two neonatal intensive care units (NICUs).
Data were collected prospectively over a 2-year period to assess risk factors among 2,935 neonates from two NICUs.
Among all neonates, in addition to low birth weight and presence of a central venous catheter, hospitalization in NICU 1 (relative risk [RR]: 1.60, 95% confidence intervals [CI]: 1.14, 2.24) was a significant predictor of BSI. In neonates with a central catheter total parenteral nutrition (TPN) was a significant risk factor for BSI (RR: 4.69, 95% CI: 2.22, 9.87). Ventilator use was a significant risk factor for CR versus non-CR BSI (RR: 3.74, 95% CI: 1.87, 7.48), and significantly more CR BSI were caused by gram-positive (77.1%) than by gram-negative organisms (61.4%), P = .03.
This study confirmed that central venous catheters and low birth weight were risk factors for neonates with late-onset healthcare-associated BSI and further elucidated the potential risks associated with TPN and ventilator use in subgroups of neonates with BSI. Additional studies are needed to examine the incremental risk of TPN among infants with central venous catheters and to understand the link between CR BSI and ventilator use. Preventive strategies for BSI in neonates in NICUs should continue to focus on limiting the use of invasive devices.
PMCID: PMC2094724  PMID: 17433941
21.  Nosocomial Bloodstream Infection and Clinical Sepsis 
Emerging Infectious Diseases  2004;10(1):76-81.
Primary bloodstream infection (BSI) is a leading, preventable infectious complication in critically ill patients and has a negative impact on patients’ outcome. Surveillance definitions for primary BSI distinguish those that are microbiologically documented from those that are not. The latter is known as clinical sepsis, but information on its epidemiologic importance is limited. We analyzed prospective on-site surveillance data of nosocomial infections in a medical intensive care unit. Of the 113 episodes of primary BSI, 33 (29%) were microbiologically documented. The overall BSI infection rate was 19.8 episodes per 1,000 central-line days (confidence interval [CI] 95%, 16.1 to 23.6); the rate fell to 5.8 (CI 3.8 to 7.8) when only microbiologically documented episodes were considered. Exposure to vascular devices was similar in patients with clinical sepsis and patients with microbiologically documented BSI. We conclude that laboratory-based surveillance alone will underestimate the incidence of primary BSI and thus jeopardize benchmarking.
PMCID: PMC3322756  PMID: 15078600
Bloodstream infection; sepsis; nosocomial infection; surveillance; benchmarking
22.  Actuarial survival of a large Canadian cohort of preterm infants 
BMC Pediatrics  2005;5:40.
The increased survival of preterm and very low birth weight infants in recent years has been well documented but continued surveillance is required in order to monitor the effects of new therapeutic interventions. Gestation and birth weight specific survival rates most accurately reflect the outcome of perinatal care. Our aims were to determine survival to discharge for a large Canadian cohort of preterm infants admitted to the neonatal intensive care unit (NICU), and to examine the effect of gender on survival and the effect of increasing postnatal age on predicted survival.
Outcomes for all 19,507 infants admitted to 17 NICUs throughout Canada between January 1996 and October 1997 were collected prospectively. Babies with congenital anomalies were excluded from the study population. Gestation and birth weight specific survival for all infants with birth weight <1,500 g (n = 3419) or gestation ≤30 weeks (n = 3119) were recorded. Actuarial survival curves were constructed to show changes in expected survival with increasing postnatal age.
Survival to discharge at 24 weeks gestation was 54%, compared to 82% at 26 weeks and 95% at 30 weeks. In infants with birth weights 600–699, survival to discharge was 62%, compared to 79% at 700–799 g and 96% at 1,000–1,099 g. In infants born at 24 weeks gestational age, survival was higher in females but there were no significant gender differences above 24 weeks gestation. Actuarial analysis showed that risk of death was highest in the first 5 days. For infants born at 24 weeks gestation, estimated survival probability to 48 hours, 7 days and 4 weeks were 88 (CI 84,92)%, 70 (CI 64, 76)% and 60 (CI 53,66)% respectively. For smaller birth weights, female survival probabilities were higher than males for the first 40 days of life.
Actuarial analysis provides useful information when counseling parents and highlights the importance of frequently revising the prediction for long term survival particularly after the first few days of life.
PMCID: PMC1315360  PMID: 16280080
23.  Nonperinatal Nosocomial Transmission of Candida albicans in a Neonatal Intensive Care Unit: Prospective Study 
Journal of Clinical Microbiology  1998;36(5):1255-1259.
Nosocomial Candida albicans infections have become a major cause of morbidity and mortality in neonates in neonatal intensive care units (NICUs). To determine the possible modes of acquisition of C. albicans in hospitalized neonates, we conducted a prospective study at Grady Memorial Hospital, Atlanta, Ga. Clinical samples for fungal surveillance cultures were obtained at birth from infants (mouth, umbilicus, and groin) and their mothers (mouth and vagina) and were obtained from infants weekly until they were discharged. All infants were culture negative for C. albicans at birth. Six infants acquired C. albicans during their NICU stay. Thirty-four (53%) of 64 mothers were C. albicans positive (positive at the mouth, n = 26; positive at the vagina, n = 18; positive at both sites, n = 10) at the time of the infant’s delivery. A total of 49 C. albicans isolates were analyzed by restriction endonuclease analysis and restriction fragment length polymorphism analysis by using genomic blots hybridized with the CARE-2 probe. Of the mothers positive for C. albicans, 3 of 10 were colonized with identical strains at two different body sites, whereas 7 of 10 harbored nonidentical strains at the two different body sites. Four of six infants who acquired C. albicans colonization in the NICU had C. albicans-positive mothers; specimens from all mother-infant pairs had different restriction endonuclease and CARE-2 hybridization profiles. One C. albicans-colonized infant developed candidemia; the colonizing and infecting strains had identical banding patterns. Our study indicates that nonperinatal nosocomial transmission of C. albicans is the predominant mode of acquisition by neonates in NICUs at this hospital; mothers may be colonized with multiple strains of C. albicans simultaneously; colonizing C. albicans strains can cause invasive disease in neonates; and molecular biology-based techniques are necessary to determine the epidemiologic relatedness of maternal and infant C. albicans isolates and to facilitate determination of the mode of transmission.
PMCID: PMC104810  PMID: 9574687
24.  Variations in rates of nosocomial infection among Canadian neonatal intensive care units may be practice-related 
BMC Pediatrics  2005;5:22.
Nosocomial infection (NI), particularly with positive blood or cerebrospinal fluid bacterial cultures, is a major cause of morbidity in neonatal intensive care units (NICUs). Rates of NI appear to vary substantially between NICUs. The aim of this study was to determine risk factors for NI, as well as the risk-adjusted variations in NI rates among Canadian NICUs.
From January 1996 to October 1997, data on demographics, intervention, illness severity and NI rates were submitted from 17 Canadian NICUs. Infants admitted at <4 days of age were included. NI was defined as a positive blood or cerebrospinal fluid culture after > 48 hrs in hospital.
765 (23.5%) of 3253 infants <1500 g and 328 (2.5%) of 13228 infants ≥1500 g developed at least one episode of NI. Over 95% of episodes were due to nosocomial bacteremia. Major morbidity was more common amongst those with NI versus those without. Mortality was more strongly associated with NI versus those without for infants ≥1500 g, but not for infants <1500 g. Multiple logistic regression analysis showed that for infants <1500 g, risk factors for NI included gestation <29 weeks, outborn status, increased acuity on day 1, mechanical ventilation and parenteral nutrition. When NICUs were compared for babies <1500 g, the odds ratios for NI ranged from 0.2 (95% confidence interval [CI] 0.1 to 0.4) to 8.6 (95% CI 4.1 to 18.2) when compared to a reference site. This trend persisted after adjustment for risk factors, and was also found in larger babies.
Rates of nosocomial infection in Canadian NICUs vary considerably, even after adjustment for known risk factors. The implication is that this variation is due to differences in clinical practices and therefore may be amenable to interventions that alter practice.
PMCID: PMC1182378  PMID: 16004613
25.  Nosocomial Infection Reduction in VLBW Infants With a Statewide Quality-Improvement Model 
Pediatrics  2011;127(3):419-426.
To evaluate the effectiveness of the California Perinatal Quality Care Collaborative quality-improvement model using a toolkit supplemented by workshops and Web casts in decreasing nosocomial infections in very low birth weight infants.
This was a retrospective cohort study of continuous California Perinatal Quality Care Collaborative members' data during the years 2002–2006. The primary dependent variable was nosocomial infection, defined as a late bacterial or coagulase-negative staphylococcal infection diagnosed after the age of 3 days by positive blood/cerebro-spinal fluid culture(s) and clinical criteria. The primary independent variable of interest was voluntary attendance at the toolkit's introductory event, a direct indicator that at least 1 member of an NICU team had been personally exposed to the toolkit's features rather than being only notified of its availability. The intervention's effects were assessed using a multivariable logistic regression model that risk adjusted for selected demographic and clinical factors.
During the study period, 7733 eligible very low birth weight infants were born in 27 quality-improvement participant hospitals and 4512 very low birth weight infants were born in 27 non–quality-improvement participant hospitals. For the entire cohort, the rate of nosocomial infection decreased from 16.9% in 2002 to 14.5% in 2006. For infants admitted to NICUs participating in at least 1 quality-improvement event, there was an associated decreased risk of nosocomial infection (odds ratio: 0.81 [95% confidence interval: 0.68–0.96]) compared with those admitted to nonparticipating hospitals.
The structured intervention approach to quality improvement in the NICU setting, using a toolkit along with attendance at a workshop and/or Web cast, is an effective means by which to improve care outcomes.
PMCID: PMC3387911  PMID: 21339273
central-line–associated bloodstream infection; nosocomial infection; quality improvement; quality-improvement toolkits; quality-improvement evaluation

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