Retrospective review of institutional data base of a single center.
The study center is located in Southern India and receives patients from a population of ~ 30 million in the state of Kerala and neighbouring regions. A detailed description of the study setting and the manner in which care is organized in the unit has been published previously .
Data Source: The study centre is a member of the International Quality Improvement Collaborative for Congenital Heart Disease (IQIC; https://iqic.chboston.org/) since 2010 . A database that includes key pre-operative, operative and postoperative variables is collected as a part of this initiative. Additionally, data was abstracted from the Medical Records Information was collected regarding demographics, diagnosis, laboratory results, culture results and antibiotic tier, dosage and duration. Those with incomplete medical records were not included in study. Permissions for collecting and publishing the data was obtained from the hospital institutional ethics committee.
We defined CPS when a pathogenic organism grew in the blood culture. Respiratory fluid, urine and sternal wound swab positivity were not included in this group. Patients who required escalation of antibiotics beyond what was used for perioperative prophylaxis for suspected blood borne sepsis based on clinical and laboratory criteria (see below) but with negative culture reports after 5 days were considered as CNS. A patient growing same organism more than once in sequential blood cultures during the ICU stay was considered as single episode of CPS. Those patients where the perioperative antibiotic was not escalated were classified as ‘normal controls.’
Antibiotics are classified into three tiers; 1st tier is cefuroxime, used as primary surgical prophylaxis for 48 hours perioperatively. We consider aminoglycosides, fluoroquinolones, macrolides, penicillins, cefoperazone-sulbactam, piperacillin tazobactam, metronidazole, trimethoprim- sulfamethoxazole as 2nd tier and meropenem, imipenem-cilastatin, tetracycline, aztreonam, minocycline, vancomycin and colistin as 3rd tier antibiotics.
Blood Culture Technique and Validation
A single blood sample was obtained by venipuncture site after careful disinfection of the skin and not from a pre-existing intravascular catheter whenever clinical sepsis was suspected prior to empirical upgrading of antibiotics on all instances. 1 to 3 ml of blood was inoculated each time into BACTEC PEDS PLUS Culture vial and stored at 2-to-25-degree Celsius. The site of collection, volume of blood collected, prior antibiotic administration with duration and dosage if any was documented in the blood culture investigation form and was transferred at the earliest to microbiology team. The BACTEC automated culture has superior bacterial isolation rate with lesser detection time in comparison to conventional methods .The microbiology team provisionally declares it as negative culture if no growth identified in the initial 48 hours, subsequent delayed positivity was also reported promptly.
Patients: All children of the age group 1 day to 18 years who underwent corrective or palliative cardiac surgical procedures from January 2020 through December 2020 were included. This study was limited to those patients in whom antibiotics were initiated specifically for presumed or proven blood stream sepsis. The common reasons to upgrade antibiotics included one or more of the following: fever (rectal temperature ≥ 38 ̊C [100.4 ̊F]) beyond 48 hours after surgery, unexplained hemodynamic instability in the form of hypotension, reduced tissue perfusion in the absence of any residual cardiac lesions or ventricular dysfunction, persistent lactic acidosis, leukopenia (< 4000/mL), marked leukocytosis (> 25000/mL), thrombocytopenia (platelet count < 50,000/ mL) and, persistent hypoglycemia. Subjects with antibiotic initiation for pneumonia, urinary infection or surgical site infection were excluded.
The outcome variable that were tested included, in-hospital mortality, duration of mechanical ventilation, duration of ICU stay and total duration of hospital stay.
Categorical variables were presented as frequency and percentage and normally distributed continuous variables were presented as mean ± SD. In situation where the continuous variables were skewed we presented the median and IQR. Pearson Chi-Square test or Fisher’s exact test was used to compare categorical variables. Independent sample t-test was used to compare the duration of antibiotics between culture negative and positive groups. Kruskal-Wallis test followed by Mann Whitney test for subgroup was used to compare the demographic variables and continuous outcome variables. Multiple binary logistic regression (Enter) method was used to estimate the odds ratio (OR) with 95% CI of risk factors for postoperative mortality. Multiple ordinary least square (OLS) linear regression model was used evaluate the relation between culture negative, culture positive, age and weight with duration of postoperative mechanical ventilation, adjusting for confounding variables. Since the postoperative stay variables were highly skewed, they were log-transformed to meet the normality assumptions required by the OLS linear regression method. The resulting parameter estimates were then back transformed to their original scale to facilitate the interpretation of the results. The back-transformed parameters can be interpreted as “median ratio”. Statistical analyses were conducted using SPSS Version 20.0 for Windows (IBM Corporation ARMONK, NY, USA).