Nosocomial infections in the pediatric intensive care units in Lithuania

Summary. Objective. The aim of the study was to collect the data on incidence rates, pathogens of nosocomial infections, and antimicrobials for treatment of nosocomial infections. Material and methods. Data were collected between March 2003 and December 2005 in five pediatric intensive care units using a modified patient-based HELICS protocol. Nosocomial infection was identified using the Centers for Disease Control definitions. All patients aged between 1 month and 18 years that stayed in the units for more than 48 hours were eligible for inclusion in this study. Results. A total of 1239 patient admissions and 7601 patient-days were evaluated. In 169 children (13.6%), 186 nosocomial infections occurred. The incidence density was 24.5 per 1000 patient-days, the incidence rate – 15.0 per 100 admissions. The highest incidence density was observed in the 6–12-year age group (31.2 per 1000 bed-days). Nosocomial infection rates per 1000 device-days were 28.8 for ventilator-associated pneumonia, 7.7 – for bloodstream infection, and 3.4 – for urinary tract infection. The most common site of infection was respiratory tract (58.8%). Secondary bacteremia developed in 18 (10.6%) patients. Haemophilus influenzae (20.1%), Acinetobacter spp. (14.2%), and Staphylococcus aureus (17.6%) were the most frequently isolated microorganisms. The most common antimicrobials used were first- and second-generation cephalosporins 74 (31.0%) and broad-spectrum penicillins 70


Introduction
Nosocomial infections (NIs) are a worldwide healthcare and public health problem, which places a substantial burden on individual patients and on the health care system and result in major complications of serious illnesses (1)(2)(3)(4). NIs are a common cause of higher morbidity, mortality, and longer stays in the hospital (4)(5)(6)(7)(8)(9). Children, hospitalized in intensive care units (ICUs), are unique population in regard to specific risk factors for NIs. Small children have enhanced susceptibility to many infections because of immaturity of their immune system. Children's exposure to environmental contamination (toys, diaper, hugging) is increased, they are treated using multidisciplinary medical and surgical approach; however, children have fewer chronic or degenerative disorders (5,10,11). The overall reported incidence of NIs ranges from 6.1% to 29.6% in the pediatric intensive care units (PICUs) (5,6,8,9,(11)(12)(13)(14)(15)(16). However, to our knowledge, there are no published data about the incidence rates of NIs in PICUs of Eastern European countries.
Here we report the data on incidence rates, pathogens of nosocomial infections, and antimicrobials prescribed for the treatment of nosocomial infections. In addition, we compare the length of stay and mortality rate in the group of patients with NIs vs. without NIs.

Material and methods
Patients and setting. Data were collected between March 2003 and December 2005 from five PICUs in Lithuania: three in the University Hospitals and two in the regional central hospitals as subunits of general ICUs. All five units, which participated in the study voluntarily, represent about 60% of all PICUs. The surveillance of NIs was carried out with permission of Lithuanian Bioethics Committee, issued in 2002.
All patients aged between 1 month and 18 years were eligible for inclusion in this analysis. All patients that stayed in the units for more than 48 hours were included.
Surveillance procedures and definitions. This report presents data from national NI surveillance system launched in 2003 in Lithuania. Participation of ICUs is voluntary, but requirement of minimum 6month surveillance time per year and not shorter than 2-month continuous data collection should be followed. A patient-based NI surveillance protocol adopted from HELICS protocol was established (17,18). Patients in departments were examined by physicians on duty, and standard data collection form was filled out where firstly general patient data (gender, age, referral place), clinical profile (medical, surgical, trauma), and patient status on admission (presence of infection, antibiotics at the time of admission, surgical operation within 1 month before admission) were indicated, and then risk factors during stay in a PICU, infection diagnosed during hospital stay, its treatment and outcome (discharge or death) were recorded daily.
The main risk factors for nosocomial infections were recorded, e.g. mechanical ventilation, arterial/ central line, urinary catheter, peripheral venous catheter, intracranial pressure device, bronchoscopy, tracheostomy), and Standard Centers for Disease Control and Prevention definitions of infections were used (19). An infection was defined as NI if it occurred 48 hours after admission to the unit or within 48 hours after discharge. In addition to site of infection, its causative pathogen was determined; secondary bacteremia, if present, and antimicrobial therapy, if prescribed, were specified.
Statistical analysis. The data from the data collection forms were checked twice, entered into a database (EpiData, version 2.1), and analyzed with EpiInfo (version 6.04d) and Statistica (version 6.0) software. The size of the sample was appropriate for statistical analysis.
NI incidence (number of NI divided by number of patients admitted), NI incidence density (number of NI divided by number of patient-days), deviceassociated rate (number of NI divided by number of device-days), and device utilization ratio (number of device-days divided by patient-days) were calculated.
The patients for analysis were divided into four age groups: infants (aged 1 month to <1 year), preschool children (1-5 years), children (6-12 years), and adolescents (>12 years). Types of NIs, incidence rates (NI incidence, NI incidence density, and deviceassociated rate), and device utilization ratios were compared among the age groups.
In addition, the sample was divided into two groups (with NIs and without NIs), and the groups were compared by age, gender, length of stay, and the mortality rate.
Categorical variables were evaluated using the chisquare (c 2 ) test. Continuous variables were evaluated using Kolmogorov-Smirnov, Mann-Whitney U, and t test as appropriate. The significance level was P<0.05.
A total number of 562 (45.4%) patients had an infection, 352 (28.4%) patients were treated with antibiotics at the time of admission to PICUs, and 157 (12.7%) were operated on within one month before the admission.

Incidence and types of nosocomial infections
One hundred sixty-nine children (13.6%) had a total of 186 nosocomial infections (NIs), 155 children (91.7%) had only one episode of NI, and 14 children (8.3%) had two or more episodes.
The incidence of nosocomial infections was 24.5 per 1000 patient-days, and the rate of NIs per 100 admissions was 15.0. No significant differences in the incidence of nosocomial infections was observed among the age groups (c 2 =3.32, df=3, P>0.05), but the highest incidence density was in the 6-12-year age group (c 2 =11.09, df=3, P=0.01) ( Table 2). There was no significant difference in NI incidence observed between genders as well (15.5% of boys vs. 14.2% of girls, P>0.05).
The most common site of NIs was respiratory tract (58.8%). There was a statistically significant domination of other lower respiratory tract infections (LRTIs) in the two age groups: 6-12 years and >12 years. However, the distribution of NIs by site in the age groups was similar (Table 3).

Pathogens of nosocomial infections
The total number of 157 (84.4%) NI cases were tested microbiologically. There was a growth of pathogens in 134 (85.4%) cases, no growth -in 8 (5.1%); the answer was missing in 15 cases (9.5%). The

Length of stay and the mortality rate
The groups of patients with NIs and without NIs were homogenous by age and gender (P>0.05).
The length of stay for patients with NIs was more  Table 4).

Discussion
Prevention of NIs is the key procedure in quality of healthcare. Accurate data on NI rates are essential for evaluation of current infection prevention activities and for planning further interventions in hospital as well as at national level (20). This is the first report on NI rates in pediatric ICUs in the Baltic region. National compulsory NI reporting system existing in Lithuania for more that 20 years was missing data on NIs in ICUs. Therefore, data from new active surveillance system were very needful. It was very important to evaluate newly obtained data by comparing with data from other studies and NI surveillance systems even if it is complicated as the criteria of NIs and data collection methods might vary. Comparison of data is quite profound in one study or surveillance system due to obvious differences between PICUs: severity of pathology, organization of work, etc. (5-7, 9, 14, 15, 21-24). Therefore, comparison of the data obtained from large databases or multicenter prospective incidence studies is more rational. Despite some limitations (hospitals are required to submit only 1 month of data, case finding methods are not specified, units are very different, etc.), the database of National Nosocomial Infections Surveillance System (NNIS) contains large amount of data from over 50 PICUs in the United States (11,25). A similar database in European Union has not been completed yet, and data from PICUs are not available (17,18).
As in most studies from PICUs (6,8,14,23) and adult ICUs (24), PNE and LRTI were most prevalent NIs and accounted for 58.8% of all NIs with minor variations in the age groups. However, there are reports from PICUs where BSI (5,7,21,22) and UTI (15) are the main sites of NIs, but in Lithuania these infections were recorded relatively rare.
The overall ventilator-associated pneumonia (VAP) incidence rate was very high when compared to data from other studies (28.8 vs. 8.9-18.7) (6,7,15,26,27). VAP rate in the age groups from >1 to £12 years (30.2-42.6) considerably exceeded the 90th percentile as compared to NNIS data (25). This points out the need to re-evaluate the current respiratory care practices, hygienic regulations, as the ventilator utilization ratio is not high when compared to NNIS datait corresponds to the 25th percentile in the age group from 1 month to £12 years and to the 50th percentile in the age group of >12 years (25).  The central line-associated BSI rate (7.7) was lower as compared to the data from the majority of reported studies (6,7,9,11,13,28) but higher than it is described in the European study (8). Similarly to VAP, the central line-associated BSI rate in the age group from >1 to £12 years (10.6-12.9) exceeded 90th NNIS percentile (25).
The urinary catheter-associated UTI rate (3.4) in general was not high as compared with reported data, which are very different across the world (1.8-25.5) (6-9, 11, 13). Only the infant group diverged with UTI rate (6.3) exceeding the 75th NNIS percentile (25). This may indicate a problem of excessive use of urinary catheters increasing the risk of UTI, whereas urinary catheter utilization ratio corresponded to the 50th percentile in the infant group and exceeded the 90th percentile in the age group of >1 year when compared to NNIS data (25). It is evident that the main risk factor for UTI is urinary catheter placement itself and its duration (29,30). It is worth noting that the low rate may reflect a problem of undiagnosed infections. Most of UTIs are not severe and self-limiting, and microbiological investigations in such cases are not performed routinely in Lithuania.
We determined rather different pathogens in our study, where H. influenzae, S. aureus, and Acinetobacter spp. were prevailing. It differs from the reported data (6,8,22,23), and it could be explained by the early onset of NIs (before the fourth day) in one-third of the patients. The other reason is the fact that the lower respiratory tract is a highly predominant site of infection. The prevalence of Candida was low (n=7, 3.4%), and it was not obtained from blood. In addition, the prevalence of MRSA was low (n=2, 5.5%).
The use of antimicrobials seems to be quite favorable. The use of penicillins and first-second generation cephalosporins accounted for 69.1% of all the cases.
Length of stay at PICUs was longer for patients with NI vs. without NI as it is reported in most studies (6)(7)(8)(9). The same applies to mortality rate. This issue is always very sensitive in clinical practice. In some reports, NI is claimed to be responsible for a higher mortality rates in PICUs (5-7, 15, 27), in some not (26,28,31). In our study, the two groups (with NIs and without NIs) were homogenous by age and by gender, but unfortunately, the severity of underlying condition was not recorded. Higher mortality rate for patients with NIs could be influenced partly by underlying pathology as well as by NIs. The pediatric index of mortality (PIM) scoring would be helpful and suitable in this case. Unfortunately, it was impossible to introduce this index from the beginning of surveillance as only one PICU was using it routinely (32,33).

Conclusions
The observed incidence density was 24.5 per 1000 patient-days, incidence rate was 15.0 nosocomial infections per 100 admissions, and it was comparable to the available data from the pediatric intensive care units of other countries. The bloodstream infection rate was 7.7 per 1000 central venous catheter-days; urinary tract infection rate was 3.4 per 1000 urinary catheter-days. The ventilator-associated pneumonia rate of 28.8 per 1000 ventilation-days was relatively too high. Haemophilus influenzae, Acinetobacter spp., and Staphylococcus aureus were the most prevalent pathogens, but the prevalence of methicillin-resistant Staphylococcus aureus was low. The first-and second-generation cephalosporins and broad-spectrum penicillins were the most common antimicrobials used in treatment of nosocomial infections. The length of stay and the mortality rate were higher in patients with nosocomial infections if compare to patients without nosocomial infections.