The basic characteristics of KP-infected patients
A total of 425 pediatric inpatients met the diagnosis criteria of invasive KP infections based on the hospital microbiology laboratory records, of whom, 248 (58.4%) neonates ≤ 28 days and 177 (41.6%) were children aged > 28 days on admission. Finally, 324 (76.2%) patients met the enrollment criteria and were included in this study and 101 (23.8%) were excluded due to unavailability of medical records (99 patients) and incomplete clinical data collection (2 patients).
Of the 324 enrolled patients, 299 (92.3%) had KP isolated from blood, 11 (3.4%) had KP isolated from CSF and 14 (4.3%) had KP isolated from both blood and CSF. On the clinical grounds and case definition, 275 (84.9%) patients were considered as HAI and 49 (15.1%) patients were considered as CAI.
Clinical features and risk factors of healthcare-associated KP infections in pediatric patients.
Among 275 patients with HAI, 154 (56%) were male; the median age was 0.6 months (IQR 0.17-6, range: 1 day-17 years) and the age distribution was as followings: 162 (58.9%) aged ≤ 28 days, 33 (12.0%) aged 29 days-2 months, 20 (7.3%) aged 3–11 months, 33(12.0%) aged 1–5 years, 27 (9.8%) aged > 5 years. Of 162 neonates, 129 (79.6%) were preterm,including 13 (10.1%) at < 28 weeks of gestational age, 75 (58.1%) at 28–31 weeks of gestational age and 41 (31.8%) at 32-37weeks of gestational age. Two hundred and eighteen (79.3%) patients had the accompanying focal organ infections, including pneumonia (119, 43.3%), meningitis (64, 23.3%), intra-abdominal infections (41, 14.9%), upper urinary tract infections (3, 1.1%) and osteomyelitis (4, 1.5%); 13 patients had 2 infection sites. Nine (3.3%) patients died in hospital and 30 (10.9%) patients were hopelessly discharged at the request of parents.
Compared to CAI patients (Table 1), the percentage of patients with underlying medical conditions was significantly greater in HAI patients, including hematologic malignancies, necrotizing enterocolitis (NEC) and prematurity (16.4% versus 2%, 9.8% versus 0%, 46.9% versus 4.1%, respectively; P < 0.05); the percentage of patients using peripherally inserted central catheter (PICC), invasive mechanical ventilation was significantly greater in HAI patients (29.8% versus 2%, 34.9% versus 2%, respectively P < 0.01). HAI patients had more episodes of meningitis than CAI patients (23.3% versus 6.1%, P < 0.01) while CAI patients had more frequency of upper urinary tract infections than HAI patients (30.6% versus 1.1%, P < 0.01). The isolation rate of CRKP strains was much higher in HAI patients than in CAI patients (40.4% versus 10.2%, P < 0.01). The poor outcomes were similar between between HAI and CAI patients (14.2% versus 8.2%, P > 0.05).
Multiple regression analysis showed that prematurity (OR:37.07, 95% CI:8.29-165.84), hematologic malignancies (odds ratio (OR:15.52, 95% CI:1.89-127.14), and invasive mechanical ventilation (OR:13.09, 95% CI: 1.66-103.56) were independent risk factors for HAI (Table 2).
Risk factors of healthcare-associated CRKP infections in pediatric patients
Compared to CSKP-infected patients (Table 3), CRKP-infected patients stayed in hospital for a longer time (39 days versus 29.5 days, P < 0.05) and received more therapies of mechanical ventilation (45.0% versus 28.0%, P < 0.05). More CRKP-infected patients developed organ dysfunction than CSKP-infected patients (36.0% versus 17.7%, P < 0.05). The poor outcomes were similar between CSKP-infected and CRKP-infected patients (14.4% versus 14%, P > 0.05).
Multiple regression analysis showed that children from rural area (OR: 1.78, 95% CI:1.06–2.99, P < 0.05), invasive mechanical ventilation (OR:1.79, 95% CI: 1.01–3.19, P < 0.05), prior antibiotic therapy before hospitalization (OR: 1.88, 95% CI:1.07–3.29, P < 0.05) and prior hospitalization in the past 30 days (OR: 2.17, 95% CI:1.26–3.73, P < 0.05) were independent risk factors for CRKP infections (Table 4).
Risk factors of poor outcomes in pediatric patients with healthcare-associated KP infections
As shown in Table 5, univariate analysis showed that invasive mechanical ventilation, any organ dysfunction and septic shock were the significant risk factors for poor outcomes. Multiple regression analysis showed that organ dysfunction was an independent risk factor for the poor outcomes (OR:2.92, [95% CI: 1.23–6.95], P < 0.05).
Antimicrobial susceptibility patterns of healthcare-associated KP isolates
As shown in Table 6, healthcare-associated KP strains showed high frequency of resistance to carbapenem as well as other clinical important antibiotics usually recommended for the treatment of Enterobacteriaceae infections, such as third-generation cephalosporins, cefepime and piperacillin/tazobactam. Also, healthcare-associated KP strains showed significantly higher frequency of resistance to clinical important antibiotics than community-acquired KP stains. Besides, healthcare-associated KP strains showed relatively higher resistance percentage to tigecycline, amikacin, ciprofloxacin and levofloxacin (12.5%-23.7%). Healthcare-associated KP strains almost remained sensitive to polymyxin B.