Pharmacokinetics of imipenem in critically ill patients during empirical treatment of nosocomial pneumonia: A comparison of 0.5-h and 3-h infusions

Background. Nosocomial pneumonia due to carbapenem-resistant Gram-negative bacteria (CRGNB) is a growing concern because treatment options are limited and the mortality rate is high. The effect of tigecycline (TGC) on nosocomial pneumonia due to CRGNB in patients who have received inappropriate initial empiric antibiotic treatment (IIAT) is unclear. Therefore, this study aimed to examine the effect of TGC on nosocomial pneumonia due to CRGNB in critically ill patients who had received IIAT. Methods. A retrospective study was conducted in an adult respiratory intensive care unit. Data were obtained and analyzed for all patients who were treated with TGC ≥ 3 days for microbiologically confirmed nosocomial pneumonia due to CRGNB and had experienced initial antibiotic failure. Clinical and microbiological outcomes were investigated. Results. Thirty-one patients with hospital-acquired pneumonia or ventilator-associated pneumonia were included in the study. The majority of the responsible organisms were carbapenem-resistant Acinetobacter baumannii (67.7%), followed by Klebsiella pneumoniae (16.1%) and Escherichia coli (9.7%). Twenty patients were treated with high-dose TGC therapy (100 mg every 12 h after a 200 mg loading dose), and the others received a standard-dose therapy (50 mg every 12 h after a 100 mg loading dose). The duration of TGC therapy was 14.3±2.8 days. The global clinical cure rate and the microbiological eradication rate were 48.4% and 61.3%, respectively. The overall ICU mortality rate was 45.2%. A higher score on the Acute Physiology and Chronic Health Evaluation II and a longer duration of IIAT were associated with clinical failure. High-dose TGC therapy had a higher clinical success rate [65.0% (13/20) versus 18.2% (2/11), P=0.023] and a lower ICU mortality rate [30.0% (6/20) versus 72.7% (8/11), P=0.031] than the standard-dose therapy. Conclusions. TGC, especially a high-dose regimen, might be a justifiable option for critically ill patients with nosocomial pneumonia due to CRGNB who have received IIAT when the options for these patients are limited.

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Clinical utility of methicillin-resistant Staphylococcus aureus nasal polymerase chain reaction assay in critically ill patients with nosocomial pneumonia

Journal of Critical Care ◽

10.1016/j.jcrc.2016.11.008 ◽

2017 ◽

Vol 38 ◽

pp. 168-171 ◽

Cited By ~ 19

Author(s):

Melanie N. Smith ◽

Michael J. Erdman ◽

Jason A. Ferreira ◽

Petra Aldridge ◽

Christopher A. Jankowski

Keyword(s):

Staphylococcus Aureus ◽

Polymerase Chain Reaction ◽

Critically Ill ◽

Nosocomial Pneumonia ◽

Critically Ill Patients ◽

Polymerase Chain Reaction Assay ◽

Clinical Utility ◽

Methicillin Resistant Staphylococcus Aureus ◽

Chain Reaction ◽

Polymerase Chain

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Nosocomial Pneumonia Elicits an Endothelial Proteinopathy: Evidence for a Source of Neurotoxic Amyloids in Critically Ill Patients

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.201801-0060le ◽

2018 ◽

Vol 198 (12) ◽

pp. 1575-1578 ◽

Cited By ~ 7

Author(s):

Mike T. Lin ◽

Ron Balczon ◽

Jean-Francois Pittet ◽

Brant M. Wagener ◽

Stephen A. Moser ◽

...

Keyword(s):

Critically Ill ◽

Nosocomial Pneumonia ◽

Critically Ill Patients

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Pharmacokinetics and intrapulmonary concentrations of high-dose tigecycline in critically ill patients with severe infections

10.21203/rs.3.rs-15408/v1 ◽

2020 ◽

Author(s):

Gennaro De Pascale ◽

Lucia Lisi ◽

Gabriella Maria Pia Ciotti ◽

Maria Sole Vallecoccia ◽

Salvatore Lucio Cutuli ◽

...

Keyword(s):

Critically Ill ◽

Nosocomial Pneumonia ◽

Critically Ill Patients ◽

Group Differences ◽

High Dose ◽

Epithelial Lining Fluid ◽

Combination Strategies ◽

Severe Infections ◽

Abdominal Infections ◽

Mic Value

Abstract Background In critically ill patients, the use of high tigecycline dosages (HD TGC) (200 mg/day) has been recently increasing but few pharmacokinetic/pharmacodynamic (PK/PD) data are available. We investigated plasmatic and pulmonary concentrations of HD TGC in the treatment of severe infections. Methods This was a single centre, prospective, observational study that was conducted in the twenty-bed mixed ICU of a 1,500- bed teaching hospital in Rome, Italy. In all patients admitted to the ICU between 2015 and 2018, who received TGC (200 mg loading dose, then 100 mg q12) for the treatment of documented infections, serial blood samples were collected to measure TGC concentrations. Moreover, epithelial lining fluid (ELF) concentrations were determined in patients with nosocomial pneumonia. Results Among the 32 non-obese patients included, 11 had a treatment failure, while the other 21 subjects successfully eradicated the infection. There were no between-group differences in terms of demographic aspects and main comorbidities. In nosocomial pneumonia, for a target AUC0-24/MIC of 4.5, 75% of the patients would be successfully treated in presence of 0.5 mg/L MIC value and all the patients obtained the PK target with MIC≤0.12 mg/mL. In intra-abdominal infections, for a target AUC0-24/MIC of 6.96, at least 50% of the patients would be adequately treated against bacteria with MIC≤0.5 mcg/mL. Finally, in skin and soft-tissue infections, for a target AUC0-24/MIC of 17.,9 only 25% of the patients obtained the PK target at MIC values of 0.5 mg/L and less than 10% were adequately treated against germs with MIC value ≥1 mcg/ml. HD TGC showed a relevant pulmonary penetration with a median and IQR ELF/plasma ratio (%) of 152.9 [73.5-386.8]. Conclusions The use of HD TGC is associated with satisfactory plasmatic and pulmonary concentrations for the treatment of severe infections due to fully susceptible bacteria (MIC<0.5 mg/L). Even higher dosages and combination strategies are required in presence of difficult to treat pathogens.

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