KPC - 3 Klebsiella pneumoniaeST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series of 30 patients

Abstract

BackgroundAbdominal surgery carries significant morbidity and mortality, which is in turn associated with an enormous use of healthcare resources. We describe the clinical course of 30 Intensive Care Unit (ICU) patients who underwent abdominal surgery and showed severe infections caused by Klebsiella pneumoniae sequence type (ST) 258 producing K. pneumoniae carbapenemase (KPC-Kp). The aim was to evaluate risk factors for mortality and the impact of a combination therapy of colistin plus recommended regimen or higher dosage of tigecycline.MethodsA prospective assessment of severe monomicrobial KPC-Kp infections occurring after open abdominal surgery carried out from August 2011 to August 2012 in the same hospital by different surgical teams is presented. Clinical and surgical characteristics, microbiological and surveillance data, factors associated with mortality and treatment regimens were analyzed. A combination regimen of colistin with tigecycline was used. A high dose of tigecycline was administered according to intra-abdominal abscess severity and MICs for tigecycline.ResultsThe mean age of the patients was 56.6 ± 15 and their APACHE score on admission averaged 22.72. Twenty out of 30 patients came from the surgical emergency unit. Fifteen patients showed intra-abdominal abscess, eight anastomotic leakage, four surgical site infection (SSI) and three peritonitis. The overall crude ICU mortality rate was 40% (12 out of 30 patients). Twelve of the 30 patients were started on a combination treatment of high-dose tigecycline and intravenous colistin. A significantly lower mortality rate was observed among those patients compared to patients treated with approved dose of tigecycline plus colistin. No adverse events were reported with high doses of tigecycline.ConclusionsCritically-ill surgical patients are prone to severe post-surgical infectious complications caused by KPC-Kp. Timely microbiological diagnosis and optimizing antibiotic dosing regimens are essential to prevent worse outcomes. Further studies and well-controlled clinical trials are needed to define the optimal treatment of infections by KPC-Kp and, more generally, carbapenem-resistant bacteria.

Acute appendicitis: should the laparoscopic approach be proposed as the gold standard? Six-year experience in an Emergency Surgery Unit

“…(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). The pitfalls of this disease are the doubtful diagnosis in its early stage in which it can be mimicking different digestive diseases, even functional, (23)(24)(25)(26)(27) and, subsequently, a possible evolution in severe peritonitis and sepsis (28)(29)(30)(31). As a consequence, although the appendectomy is considered a simple and safe procedure, a reliable diagnosis and a safe and correct surgical procedure are needed (32).…”

Pharmacodynamic and pharmacokinetic considerations in the treatment of critically Ill patients infected with carbapenem-resistant Enterobacteriaceae

“…88 The greatest increased risk was in patients with ventilatorassociated pneumonia (VAP), a non-FDA approved indication but a common type of CRE infection. PK-PD analysis from a hospital-acquired pneumonia study showed the mean AUC observed in patients with VAP was 15% lower and the MIC 50 and MIC 90 were higher compared to patients without VAP and therefore the median fAUC/MIC ratios were only 1.73 and 4.39 for patients with VAP and HAP, respectively. 87 A subsequent phase 2 study in patients with HAP evaluating 2 higher dose regimens of tigecycline suggested better PK-PD target attainment and clinical efficacy compared to standard doses although the small number of patients enrolled limits the interpretation of the results.…”

“…100 Achievement of this PK-PD target can be challenging in treating infections due to CRE due to the elevated MICs. For example, the CLSI breakpoint for amikacin is 16 mg/ml and the MIC 90 for CRE isolates is often at the breakpoint or above. 93 Therefore to achieve the PK-PD target of a peak concentration 8-10 times the MIC, the goal peak concentration would be 128-160 mg/ml.…”

“…In a series of 30 patients with severe intra-abdominal infections due to CRE patients treated with high-dose tigecycline (200 mg £ 1, followed by 100 mg Q12) plus colistin had a lower unadjusted ICU mortality rate of 8.3% compared to standard-dose tigecycline plus colistin (61.1%, p D 0.0005). 90 A retrospective cohort of patients with VAP due to MDR bacteria (most commonly KPC producing K. pneumoniae and carbapenem-resistant A. baumannii) showed high dose tigecycline was an independent predictor of clinical cure (OR 6.25, 95%CI 1.59-24.57) but had no impact on ICU mortality. 91 A third retrospective cohort of 44 CRE infections, mostly patients with pneumonia or urinary tract infections, demonstrated no mortality benefit from higher tigecycline doses in critically ill patients.…”

“…In a study of CRE from 18 different European countries from 2010 to 2013, the MIC 50 and MIC 90 for tigecycline were 0.5 mg/ml and 2 mg/ml respectively. 81 The percentage of isolates susceptible depended on the antimicrobial susceptibility criteria used; 88.6% were susceptible by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) susceptibility breakpoint of 1 mg/ml versus 98.6% susceptible using the Food and Drug Administration susceptibility breakpoint criteria of 2 mcg/ml.…”