Pandrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii infections: characteristics and outcome in a series of 28 patients.

We describe the characteristics and outcome of pandrug-resistant (PDR) Gram-negative bacterial infections (23 Klebsiella pneumoniae isolates, 3 Pseudomonas aeruginosa and 3 Acinetobacter baumannii) of hospitalised patients at a tertiary-care centre (1 January 2006-31 May 2007). The site of infection was central venous catheter-related in 5 of 24 patients with clinical infection, bacteraemia in 5, the respiratory system in 5, surgical site in 5, the urinary system in 2, the ascitic fluid in 1 and the central nervous system in one. Twenty of 24 patients with infection received an antibiotic regimen containing colistin (in combination with meropenem in 8 patients). The overall in-hospital mortality was 41.7% (10/24); 8 patients died because of the PDR infection (infection-related mortality 33.3%). Significant co-morbidity was present not only in the patients who died but also in survivors. PDR Gram-negative bacterial infections are associated with considerable mortality, although not as high as expected given the fact that the isolates were resistant to all tested antibiotics, including polymyxins. Antibiotics that are ineffective in vitro may prove life-saving for some of these patients, especially combination regimens containing colistin.

Aerosolized colistin as adjunctive treatment of ventilator-associated pneumonia due to multidrug-resistant Gram-negative bacteria: a prospective study.

BACKGROUND: Ventilator-associated pneumonia (VAP) remains the leading cause of death in patients with intensive care unit (ICU) acquired infections associated with an attributable mortality around 30%. Increasing antimicrobial resistance in patients with VAP challenges intensivists to search for alternative therapeutic options. There is scarcity of data in the literature concerning the administration of aerosolized colistin in critically ill patients with VAP due to multidrug-resistant (MDR) Gram-negative pathogens. METHODS: To assess the safety and effectiveness of aerosolized colistin as an adjunctive to the intravenous antimicrobial therapy for the treatment of VAP due to MDR Gram-negative pathogens, we prospectively examined all patients, who received inhaled colistin. RESULTS: Sixty critically ill patients with a mean APACHE II score 16.7, received aerosolized colistin for the treatment of VAP due to MDR pathogens [Acinetobacter baumannii (37/60 cases), Pseudomonas aeruginosa (12/60 cases) and Klebsiella pneumoniae strains (11/60 cases)]. Half of the isolated pathogens were susceptible only to colistin. Mean (+/-SD) daily dosage of aerosolized colistin was 2.2 (+/-0.7) million international units (IU). All patients received 2946 inhalations of colistin and the mean duration of administration was 16.4 days. Fifty-seven patients received concomitant intravenous treatment with colistin or other antimicrobial agents. Bacteriological and clinical response of VAP was observed in 50/60 (83.3%) patients. No adverse effects related to inhaled colistin were recorded. All cause hospital mortality was 25% while mortality attributable to VAP was 16.7%. CONCLUSIONS: Aerosolized colistin may be considered as adjunctive to intravenous treatment in patients with VAP due to MDR Gram-negative bacteria susceptible to colistin in critically ill patients. Although colistin is safe and effective, the best route of administration remains unclear. In addition, controlled comparative studies are needed to establish its effectiveness and safety.

Risk factors of carbapenem-resistant Klebsiella pneumoniae infections: a matched case control study.

BACKGROUND: Carbapenems are frequently used to treat infections due to extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Thus, the emergence of infections due to carbapenem-resistant K. pneumoniae (CRKp) is a major public health concern. OBJECTIVES: To identify risk factors associated with the development of CRKp infections. METHODS: We conducted a matched case-control study in two hospitals (Henry Dunant Hospital, Athens, Greece and University Hospital of Heraklion, Crete, Greece). The controls were selected among patients with carbapenem-susceptible K. pneumoniae (CSKp) and were matched with CRKp cases for site of infection. RESULTS: One hundred and six patients were included in our study (53 cases and 53 controls). Mortality was 30.1% and 33.9% for patients with CRKp and CSKp infections, respectively (P = 0.83). Bivariable analysis showed that exposure to anti-pseudomonas penicillins (P = 0.004), carbapenems (P = 0.01), quinolones (P < 0.001) and glycopeptides (P < 0.001), as well as admission to the intensive care unit (P = 0.002), tracheostomy (P = 0.02), chronic obstructive pulmonary disease (P = 0.04), surgery with use of foreign body (P = 0.04) and mechanical ventilation (P = 0.02) were associated with CRKp infection. The multivariable analysis showed that exposure to fluoroquinolones [odds ratio (OR) 4.54, 95% confidence intervals (CIs) 1.78-11.54, P = 0.001] and exposure to antipseudomonal penicillins (OR 2.57, 95% CI 1.00-6.71, P = 0.04) were independent risk factors for CRKp infections. CONCLUSIONS: Our data suggest that prior exposure to fluoroquinolones and antipseudomonal penicillins are independent risk factors for the development of CRKp infections.

Soluble triggering receptor expressed on myeloid cells 1 as an anti-inflammatory mediator in sepsis.

OBJECTIVE: To define the significance of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in the septic cascade by comparing its kinetics to those of other proinflammatory mediators and of interleukin (IL) 10. DESIGN: Prospective study in a tertiary unit. PATIENTS: Blood was sampled from 90 patients with septic syndrome due to ventilator-associated pneumonia for 7 days after the appearance of symptoms. Concentrations of tumor necrosis factor (TNF) alpha, IL-6, IL-8, IL-10, and sTREM-1 were determined by enzyme-linked immunosorbent assay. RESULTS: Serum levels of TNFalpha, IL-6, IL-10, and sTREM-1 were higher in nonsurvivors than in survivors; similar differences were not found for IL-8. Positive correlations were found between the ratios IL-10/TNFalpha and sTREM-1/TNFalpha, between IL-10/IL-6 and sTREM-1/IL-6, and between IL-10/IL-8 and sTREM-1/IL-8. Median values of IL-10/TNFalpha upon presentation of sepsis, severe sepsis, and septic shock were 3.21, 2.16, and 2.86, respectively (NS). Respective values for sTREM-1/TNFalpha were 21.28, 7.33, and 27.78 (p=0.047 between sepsis and severe sepsis, p=0.003 between severe sepsis and septic shock). CONCLUSIONS: sTREM-1 follows the kinetics of IL-10 and should therefore be considered an anti-inflammatory mediator in sepsis. Decreased ratios of sTREM-1/TNFalpha might determine transition from sepsis to severe sepsis and from severe sepsis to septic shock.