INTRODUCTION
Nosocomial infection (NI) is a prevalent global health problem, particularly in pediatric intensive care units (PICU), and is associated with high mortality and morbidity, prolonged hospital stays, and high costs (1,2). There are numerous risk factors for NIs in critically ill children. In PICUs, there is frequent utilization of invasive medical devices, including endotracheal tubes (ETTs), central venous catheters (CVCs), and urine catheters. It is well-recognized that these devices increase the risk of NI (3).
The risk of nosocomial sepsis among critically ill children hospitalized in the PICU for more than two weeks is 50%. Although prevention bundles can reduce NI rates, this risk cannot be eliminated (4). Patients with NIs were found to have higher rates of poor outcomes and organ dysfunction. The overall mortality rate of NIs in children is estimated to be 11% (5). However, different factors, such as the presence of multiresistant microorganisms, affect prognosis, as shown in the literature (6).
Our study compared the clinical and demographic characteristics, laboratory parameters, and prognostic factors of NIs in children hospitalized in tertiary PICUs.
METHODS
This retrospective study was conducted in the PICU at Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences Türkiye. Healthcare provision for children aged from 1 month to 18 years is provided in our PICU, which is equipped with 12 beds, 12 ventilators, 5 Prismaflex™ hemofiltration machines (Baxter, USA), and 9 isolation rooms.
A retrospective evaluation of 48 pediatric patients aged 1 month to 18 years who had been admitted between February 2022 and January 2023, if they met the criteria for NI, was included in the study. Patients who did not meet these criteria were excluded from the study. In our 12-bed PICU, 456 patients were hospitalized and followed up during the study period.
The Center for Disease Control criteria were used for the diagnosis of NI. An infection was defined as nosocomial when it occurred 48 hours (h) after admission to the PICU, and there was no evidence that the infection was present or incubated at the time of admission to the PICU. Children were evaluated for catheter-related bloodstream infection (CRBSI), ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infections (CAUTI) (7).
CRBSI was defined as 2 positive blood cultures and the presence of one of the following symptoms in the case of a positive blood culture for a known pathogen unrelated to an infection at another site or commensal organisms: fever (>38 °C), chills at the insertion site, hypotension, or the appearance of infection. To be included in this study, the patient had to have a CVC within 48 h before this event (5).
We obtained informed consent from all parents before hospitalization and during all procedures. University of Health Sciences Türkiye, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital Non-invasive Research Ethics Committee approval was obtained from the hospital (decision no: 29, date: 15.02.2023). This study was conducted in accordance with the ethical rules of the Declaration of Helsinki Principles.
A detailed form was used for data collection regarding the patient’s age, gender, length of stay in the PICU, duration of invasive mechanical ventilation (IMV), extracorporeal treatment requirement, inotropic treatment, laboratory parameters on the day of NI detection, treatment outcomes, and mortality. The blood sampling data of all cases were measured at almost the same time from the onset, and the worst value in the first 24 h of admission was recorded. Complete blood count, serum albumin, lactate dehydrogenase; procalcitonin (PCT), C-reactive protein (CRP) levels, and blood gas analysis on admission were retrospectively recorded from our electronic health information system. For the calculation of the Pediatric Risk of Mortality III (PRISM III) score, data from 16 variables regarding temperature, systolic blood pressure, heart rate, partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, Glasgow coma score, pupillary reaction, prothrombin time and activated partial thromboplastin time, serum creatinine, serum urea nitrogen, serum potassium, blood glucose, and serum bicarbonate levels, white blood cell and platelet counts were recorded within 24 h of PICU admission (8).
To detect pathogens in patients, double blood cultures were obtained from two sites at admission, and other biological samples were also collected for culture, including sputum, pleural effusion, ascites, urine, feces, pus, and others, according to the suspected infection site. Double blood cultures, including those of the CVC and peripheral vein, were taken in patients with suspected catheter infection. The volume of blood collected was determined according to the weight of the patient (9).
For the diagnosis of VAP, tracheobronchial samples were collected via deep tracheal aspirates from ETTs using a closed aspiration technique, and urine samples were aseptically aspirated from the urinary catheter sampling port. The number of colony-forming units (CFU/mL) in urine culture was considered to be more than 105 CFU/mL (7).
Statistical Analysis
SPSS statistical software 20.0 for Windows was used for statistical analyzes numbers, frequencies (%), ratios, medians, and standard deviation values were used in the descriptive statistics of the data. The distribution of variables was checked using the Kolmogorov-Smirnov test. During the analysis of quantitative data, t-tests and Mann-Whitney U tests were used. The c2 test was used to compare categorical variables, and the Fisher Exact test was used when chi-square conditions could not be met.
RESULTS
During the study period, 48 of 456 patients with NI were included. The gender distribution was about equal. The median age of the patients was 32 months. Respiratory diseases (50%) such as pneumonia and asthma attacks were the most common reasons for admission to the PICU, followed by sepsis (22.9%) and trauma (12.5%). The median length of stay in the PICU was 25 days, ranging from 7 to 114 days, and 93.8% had hospitalizations longer than 7 days. The median PRISM III score was 8 (0-30). IMV was required in 41 patients (85.4%), and the median duration of IMV was 13 (3-102) days. Inotropic agents were used in 23 patients (47.9%). Fifteen patients (31.3%) underwent therapeutic plasma exchange (TPE), and 7 patients (14.6% of the total) had continuous renal replacement therapy (CRRT) (Table 1).
The most common pathogens identified were Gram-negative bacteria (33.3%) and fungus (27.1%) (Table 1). The rates of CRBSI, VAP, and CAUTI were 56.2%, 25%, and 18.7%, respectively (Table 2). The most frequent pathogens were Pseudomonas aeruginosa, Klebsiella species, and Candida species.
The mortality rate was 18.8%. According to the prognostic outcome in the PICU, patients were divided into the survival group (n=39) and the non-survival group (n=9). The requirement for CRRT was significantly higher in the non-survival group (p=0.017). Patients had similar prolonged PICU stay rates and requirements of IMV, TPE, and inotropic agents (p=0.472, p=0.320, p=0.432, p=0.068) (Table 3). PCT (p=0.015), and procalcitonin/albumin ratio (PAR) (p=0.016) were also higher in the non-survival group than those in the survival group (Table 4). Receiver operating characteristic (ROC) curves were used to predict mortality with PCT and PAR. According to ROC analysis, the cut-off values for PCT and PAR were found to be 1.705 (p=0.015), and 0.538 (p=0.016) respectively (Table 5, Figure 1).
DISCUSSION
Children admitted to the PICU are particularly susceptible to NIs because of the high prevalence of the use of invasive devices during their hospitalization (10). NI is a significant cause of morbidity and mortality as well as a serious financial burden. The overall incidence of NI in our PICU was 10.5%, similar to the results reported in other studies. As in most pediatric studies, we found CRBSI to be the most frequent NI (11-13).
We found that Gram-negative bacteria and fungus were more common in NI. Several studies have found that Gram-negative bacteria are more frequently isolated than Gram-positive bacteria, despite conflicting findings regarding pathogens (14). The reason for the high incidence of fungal infections in this study may be the inclusion of atypical agents.
Most patients had prolonged stays in the PICU. This result was consistent with the literature and could be explained by the lengthier stay, more frequent invasive operations, and increased patient contact with medical staff (15,16). Furthermore, the adverse hemodynamic consequences of NI may worsen organ dysfunction in critically ill pediatric patients and escalate the requirement for supportive care (3).
Mortality of NI in our study was 18.8%, which is similar to that reported in developing countries and higher than that reported in developed counties. Mortality rates in developing countries ranged from 20% to 38%, whereas they were 7.7 % to 10% in developed countries (11,14,17-19).
Another remarkable aspect of our data is that there was no statistically significant difference when comparing non-survival and survival patients for other treatment modalities. The adverse hemodynamic consequences of NI may worsen organ dysfunction in critically ill pediatric patients and escalate the requirement for supportive care (3). There were not significant differences in terms of the length of PICU stay, requirement of TPE, or inotropic agents. However, non-survival patients had a greater requirement for CRRT. Presumably, in terms of the requirement of these treatment modalities, patients with NI should be fully compared with patients hospitalized in the PICU.
Along with cultures, conventional and widespread biomarkers, such as CRP and leukocyte count, are generally regarded as valuable for the diagnosis of infection (20). This particular approach is considered insufficient for early diagnosis because it may take between 24 and 72 h to obtain culture results. Given that delays in diagnosis may increase the risk of mortality, it is necessary to develop quicker and more effective diagnostic markers.
PCT demonstrated a high level of accuracy in predicting the presence of bacteremia in cases of infection. Consequently, it is advisable to use PCT in the assessment of bacterial infection and sepsis among critically ill patients because it has been found to potentially correlate with poor outcomes in patients (21-23). Moreover, albumin serves as a robust indicator of clinical disease outcomes because of its tendency to decrease during acute infections (24,25). There is a significant correlation between PCT and albumin. Therefore, the co-occurrence of PCT positivity and albumin negativity serves as a prognostic indicator in adult patients susceptible to bacterial infection. Some studies have suggested that PAR is a rapid and relatively inexpensive biomarker that can be used as an early marker to differentiate severe NIs (20,26). Consistent with the literature, we found that PCT levels and PAR of non-survival patients were significantly higher than those of survival patients.
The main limitations of this study were the small number of cases compared with studies in adults and the inclusion of only one tertiary center. The inclusion of multiplecenters could provide additional information and identify other prognostic factors in NIs among children. Second, the low positivity and lack of standardization in culture collection time may have affected the results of pathogen identification. Furthermore, our study did not describe all NIs, such as surgical incision infections.
CONCLUSION
NIs are an important preventable cause of increased morbidity and mortality in critically ill children. This prompts the question, as clinicians, of what we can do to reduce NIs. Risk factors should be considered in patients who cannot be changed, such as the underlying disease. Other modifiable risk factors for NIs will likely be the focus of efforts to enhance patient care.
ETHICS
Ethics Committee Approval: University of Health Sciences Türkiye, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital Non-invasive Research Ethics Committee approval was received from the hospital (decision no: 29, date: 15.02.2023).
Informed Consent: We obtained informed consent from all parents before hospitalization and during all procedures.
Authorship Contributions
Concept: C.D., K.B.G., Design: K.B.G., Data Collection or Processing: E.G.Ş., Y.Y.C., Analysis or Interpretation: C.D., A.S., Literature Search: C.D., E.G.Ş., Y.Y.C., Writing: C.D., F.V.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declare that this study received no financial support.