Clinical Characteristics and Risk Factors Associated with Secondary Bloodstream Infection in Patients with Intensive Care Unit-Acquired Pneumonia Due to Carbapenem-Resistant Klebsiella Pneumoniae
Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a critical global health threat due to its resistance to nearly all beta-lactam antibiotics, leading to limited therapeutic options and high mortality rates. Patients in intensive care units (ICUs) are particularly vulnerable to CRKP infections, which commonly manifest as pneumonia, urinary tract infections (UTIs), and bloodstream infections (BSIs). Among these, BSIs are especially lethal, with mortality rates ranging from 39% to 82%. Secondary BSIs originating from primary infections, such as pneumonia, account for approximately 50% of CRKP-associated BSIs. Despite previous investigations into risk factors for CRKP infections, the specific predictors of secondary BSI development in ICU-acquired CRKP pneumonia remain inadequately understood. This study aimed to identify clinical characteristics, risk factors for 28-day mortality, and predictors of secondary CRKP-BSI in critically ill patients with ICU-acquired CRKP pneumonia.
Study Design and Patient Population
This retrospective cohort study included 76 patients admitted to the respiratory ICU of the First Affiliated Hospital of Soochow University, China, between January 2017 and September 2019. Inclusion criteria required at least two positive CRKP cultures from lower respiratory tract specimens (e.g., sputum, endotracheal aspirates, bronchoalveolar lavage fluid) obtained ≥48 hours after ICU admission. Cases with incomplete records or colonization (positive cultures without systemic inflammation) were excluded. CRKP was defined by minimum inhibitory concentrations (MICs) of ≥4 mg/L for meropenem or imipenem, or ≥2 mg/L for ertapenem. ICU-acquired pneumonia and secondary BSI were diagnosed based on clinical, laboratory, and microbiological criteria.
Clinical and Laboratory Data Collection
Demographic data, comorbidities, ICU exposures (e.g., mechanical ventilation, central venous catheters), invasive procedures (e.g., bronchoscopy, urethral catheterization), and laboratory parameters were extracted from electronic records. Severity scores, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA), were calculated at infection onset. Biomarkers such as procalcitonin (PCT), C-reactive protein (CRP), leukocyte counts, neutrophil counts, lymphocyte counts, and platelet counts were analyzed. Treatment regimens, particularly colistin use (500,000 units every 12 hours), and 28-day mortality outcomes were recorded.
Secondary CRKP-BSI: Incidence and Risk Factors
Among the 76 patients with ICU-acquired CRKP pneumonia, 23.7% (18/76) developed secondary CRKP-BSI. Patients with BSI exhibited significantly higher rates of fever (100% vs. 77.6%, P<0.05), septic shock (83.3% vs. 46.6%, P<0.05), and concurrent CRKP UTIs (44.4% vs. 6.9%, P<0.05) compared to non-BSI patients. Severity scores were markedly elevated in the BSI group: median APACHE II scores were 25.50 (interquartile range [IQR]: 17.75–31.00) versus 13.00 (IQR: 10.00–18.00) in non-BSI patients (U = 136.00, P<0.001), and median SOFA scores were 9.50 (IQR: 6.75–12.00) versus 4.00 (IQR: 3.00–7.00) (U = 219.00, P<0.001). Laboratory findings revealed pronounced lymphopenia (median lymphocytes: 0.37 vs. 0.71 × 10⁹/L, U = 340.50, P=0.027) and thrombocytopenia (median platelets: 57.50 vs. 159.00 × 10⁹/L, U = 178.00, P<0.001) in BSI patients. Elevated inflammatory markers were also observed, with PCT levels of 2.72 ng/mL (BSI group) versus 0.39 ng/mL (non-BSI group) (U = 288.50, P=0.011) and CRP levels of 131.50 mg/L versus 94.15 mg/L (U = 326.00, P=0.025).
Multivariate logistic regression identified two independent predictors of secondary BSI: thrombocytopenia (odds ratio [OR]: 0.984; 95% CI: 0.970–0.998; P=0.028) and higher APACHE II scores (OR: 1.185; 95% CI: 1.024–1.373; P=0.023). Septic shock, UTIs, and bronchoscopy were significant in univariate analysis but not retained in the final model.
28-Day Mortality: Predictors and Survival Outcomes
The overall 28-day mortality rate was 42.1% (32/76). Non-survivors had higher rates of septic shock (65.6% vs. 22.7%, P<0.001), secondary BSI (56.3% vs. 6.8%, P<0.001), lymphopenia (median lymphocytes: 0.37 vs. 0.74 × 10⁹/L, P=0.001), and thrombocytopenia (median platelets: 80.50 vs. 163.50 × 10⁹/L, P=0.002). APACHE II (median: 20.00 vs. 13.00, P=0.001) and SOFA scores (median: 8.00 vs. 4.00, P=0.001) were significantly elevated in non-survivors.
Multivariate analysis confirmed septic shock (OR: 7.955; 95% CI: 1.406–45.000; P=0.019), secondary BSI (OR: 10.308; 95% CI: 1.339–79.381; P=0.025), and lymphopenia (OR: 0.071; 95% CI: 0.008–0.625; P=0.017) as independent risk factors for 28-day mortality. Kaplan-Meier survival curves demonstrated stark contrasts: patients with secondary BSI had a 22.2% survival rate versus 77.6% in non-BSI patients (P<0.001), and those with septic shock had a 42.9% survival rate versus 91.2% in patients without shock (P<0.001).
Impact of Colistin Therapy on Outcomes
Colistin-based regimens were associated with improved survival in BSI patients. Among secondary BSI cases, 28-day mortality was 66.67% in colistin-treated patients versus 100% in those not receiving colistin (P<0.001). Conversely, in non-BSI patients, colistin therapy did not significantly reduce mortality (29.4% vs. 19.5%, P=0.546), likely due to lower baseline disease severity.
Discussion and Clinical Implications
This study highlights the grave prognosis of ICU-acquired CRKP pneumonia complicated by secondary BSI and septic shock. The high mortality observed aligns with prior reports, emphasizing the need for early recognition and aggressive management of these conditions. Thrombocytopenia and elevated APACHE II scores were critical predictors of secondary BSI, reflecting the interplay between host immune compromise, disease severity, and CRKP virulence. Lymphopenia, a marker of immunosuppression and systemic inflammation, further compounded mortality risk.
The survival benefit of colistin in BSI patients underscores its role as a salvage therapy for CRKP infections, particularly in bacteremic cases. However, the lack of mortality reduction in non-BSI patients suggests that colistin’s efficacy may be most pronounced in severe infections. Emerging therapies, such as ceftazidime-avibactam and meropenem-vaborbactam, offer promise for improving outcomes, though further studies are needed to validate their utility in ICU settings.
Limitations and Future Directions
This study’s retrospective design and single-center cohort limit generalizability. Larger, prospective multicenter studies are warranted to confirm these findings and refine risk stratification models. Additionally, genomic analyses of CRKP isolates could elucidate strain-specific virulence factors influencing BSI development and mortality.
DOI: https://doi.org/10.1097/CM9.0000000000001444
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