Oral administration of gentamicin for prophylaxis of KPC-producing Klebsiella pneumoniae gut colonization in patients treated with a novel parenchymal-sparing liver surgery: the GEN Gut study (original) (raw)

Oral decontamination with aminoglycosides is associated with lower risk of mortality and infections in high-risk patients colonized with colistin-resistant, KPC-producing Klebsiella pneumoniae

Journal of Antimicrobial Chemotherapy, 2016

Invasive infections caused by KPC-producing Klebsiella pneumoniae (KPCKP) are associated with very high mortality. Because infection is usually preceded by rectal colonization, we investigated if decolonization therapy (DT) with aminoglycosides had a protective effect in selected patients. Methods: Patients with rectal colonization by colistin-resistant KPCKP who were at high risk of developing infection (because of neutropenia, surgery, previous recurrent KPCKP infections or multiple comorbidities) were followed for 180 days. Cox regression analysis including a propensity score was used to investigate the impact of the use of two intestinal decolonization regimens with oral aminoglycosides (gentamicin and neomycin/streptomycin) on mortality, risk of KPCKP infections and microbiological success. The study was registered with ClinicalTrials.gov (NCT02604849). Results: The study sample comprised 77 colonized patients, of which 44 (57.1%) received DT. At 180 days of follow-up, decolonization was associated with a lower risk of mortality in multivariate analyses (HR 0.18; 95% CI 0.06-0.55) and a lower risk of KPCKP infections (HR 0.14; 95% CI 0.02-0.83) and increased microbiological success (HR 4.06; 95% CI 1.06-15.6). Specifically, gentamicin oral therapy was associated with a lower risk of crude mortality (HR 0.15; 95% CI 0.04-0.54), a lower risk of KPCKP infections (HR 0.86; 95% CI 0.008-0.94) and increased microbiological response at 180 days of follow-up (HR 5.67; 95% CI 1.33-24.1). Neomycin/streptomycin therapy was only associated with a lower risk of crude mortality (HR 0.22; 95% CI 0.06-0.9). Conclusions: Intestinal decolonization with aminoglycosides is associated with a reduction in crude mortality and KPCKP infections at 180 days after initiating treatment.

Risk factors for KPC-producing Klebsiella pneumoniae enteric colonization upon ICU admission.

J Antimicrob Chemother. 2012 Dec;67(12):2976-81., 2012

"OBJECTIVES: To identify risk factors for KPC-producing Klebsiella pneumoniae (KPC-Kp) enteric colonization at intensive care unit (ICU) admission. Recently, the emergence and spread of KPC-producing Enterobacteriaceae in healthcare facilities has become an important issue. Understanding the extent of the reservoir in ICUs may be important for targeted intervention. METHODS: A prospective observational study of all patients (n = 405) admitted to an ICU was conducted during a 22 month period. Rectal samples were taken from each patient within 12-48 h of admission and were inoculated in selective chromogenic agar. K. pneumoniae isolates were characterized by standard methodology. Antibiotic susceptibility testing (agar disc diffusion method), MIC determination (Etest), identification of carbapenemase-producing isolates (Hodge test) and determination of KPC production (boronic acid-imipenem disc test) were performed. The presence of the bla(KPC) gene was confirmed by PCR. Epidemiological data were collected from the ICU computerized database and patient chart reviews. RESULTS: Upon ICU admission, 52/405 (12.8%) patients were colonized with KPC-Kp that was associated with the following risk factors: previous ICU stay (OR 12.5; 95% CI 1.8-86.8), chronic obstructive pulmonary disease (OR 6.3; 95% CI 1.2-31.9), duration of previous hospitalization (OR 1.3; 95% CI 1.1-1.4), previous use of carbapenems (OR 5.2; 95% CI 1.0-26.2) and previous use of β-lactams/β-lactamase inhibitors (OR 6.7; 95% CI 1.4-32.9). For patients previously hospitalized on peripheral wards the following risk factors were identified: duration of hospitalization prior to ICU admission (OR 1.1; 95% CI 1.1-1.3), number of comorbidities (OR 1.9; 95% CI 1.1-3.5) and number of antimicrobials administered (OR 2.1; 95% CI 1.3-3.3). CONCLUSIONS: The high prevalence of KPC-Kp enteric carriage in ICU patients at admission dictates the importance of implementation of infection control measures and strict antibiotic policies prior to ICU transfer."

Author's response to reviews Title: KPC - 3 Klebsiella pneumoniae ST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series

2013

Objective: 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 pl us recommended regimen (100 mg initially, followed by 50 mg every 12 hours) or higher dosage of tigecycline . Methods: A prospective assessment of severe monomicrobial KPC-Kp infections occurring after open abdominal surgery carried out from August 2011 to August 2012 in t he same hospital by different surgical teams is presented. Clinical and surgical ch racteristics, microbiological and surveillance data, factors associated with mortality and treatm ent 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...

Prospective study comparing the efficacy of prophylactic parenteral antimicrobials, with or without enteral decontamination, in patients with acute liver failure

Liver Transplantation, 1996

The efficacy of prophylactic parenteral antibacterials, with or without selective decontamination of the digestive tract, was compared in patients with acute liver failure (ALF) or severe acetaminophen hepatotoxicity. One hundred eight patients were randomized on admission to receive intravenous ceftazidime and flucloxacillin, plus either oral and enteral decontamination with colistin, tobramycin, and amphotericin B (group 1), or enteral amphotericin B alone (group 2). The two groups were comparable with respect to age, gender, etiology, coma grade on admission, international normalization ratio, presence of renal failure, Acute Physiology and Chronic Health Evaluation II score, and indicators of poor prognosis. Patients were monitored for clinical and microbiological evidence of infection. There were 15 episodes of infection in 10 of 47 patients (21%) in group 1 and 17 episodes in 12 of 61 patients (20%) in group 2. No differences in incidence, site, and causative organisms of infection were observed between the two groups. Overall, the incidence of infection was significantly higher in patients who developed encephalopathy than in those who did not. In patients who on arrival were not encephalopathic, the development of infection was associated with progression to coma. Duration of Liver Intensive Care Unit (LICU) stay was an independent risk factor for the development of infection. Parenteral antibiotics are effective at reducing the risk of infection in patients with ALF; enteral decontamination provided no additional benefit. Copyright © 1996 by the American Association for the Study of Liver Diseases.

Gastrointestinal colonization by KPC-producing Klebsiella pneumoniae following hospital discharge: duration of carriage and risk factors for persistent carriage

Clinical Microbiology and Infection, 2013

The natural history of KPC-producing Klebsiella pneumoniae (KPC KP) carriage is unknown. We aimed to examine the duration of KPC KP carriage following hospital discharge and to study the risk factors for persistent carriage. A cohort of 125 KPC KP carriers was followed monthly for between 3 and 6 months after discharge from an acute-care hospital. Rectal swabs and data were collected at baseline and at each visit. KPC KP was detected by culture and direct bla KPC PCR. Acquisition time was regarded as the earliest date of KPC KP isolation. Resolution of carriage was defined as a negative KPC KP test in at least two consecutive samples. Analyses were separated for recent (<4 months) (REC, 75 patients) and remote (! 4 months) (REM, 50 patients) acquisition groups. Risk factors for persistent carriage were examined by survival analyses for the REC group and by prevalence methods for the REM group. The mean age of patients was 67.5 years and 49.6% were male. Forty-six (61%) patients in the REC group and 14 (28%) in the REM group were persistent carriers (p < 0.001). A significant risk factor for persistent carriage identified in both the REC and REM groups was the presence of any catheter (p < 0.05). Unique risk factor groups included long-term care facility (LTCF) residence (p < 0.01) and a low functional status as measured by the Barthel's index (p < 0.05) in the REC group and high Charlson's score in the REM group (p < 0.05). Out of the entire 100 patients who had at least one negative sample, only 65 remained negative on subsequent cultures. In conclusion, persistent carriage of KPC KP is associated with catheter use and a low functional status; it is more common in patients with recent acquisition and is related to LTCF stay. A single negative KPC KP test is insufficient to exclude persistent carriage.

Long term, low-dose tigecycline to treat relapsing bloodstream infection due to KPC-producing Klebsiella pneumoniae after major hepatic surgery

International Journal of Infectious Diseases, 2015

A 68 years-old male underwent right hepatectomy, resection of biliary carrefour and left hepaticjejunostomy for a Klatskin cancer. The post-operative course was complicated by biliary abscesses with relapsing bloodstream infections due to KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp). A two-week course of combination antibiotic therapy failed to obtain source control and bacteremia relapsed. Success was obtained with a regimen of tigecycline 100 mg qd for two months, followed by tigecycline 50 mg qd for six months, then 50 mg every 48 hours for three months. No side effects were reported.

Collateral damage of using colistin in hospitalized patients on emergence of colistin-resistant Escherichia coli and Klebsiella pneumoniae colonization and infection

Antimicrobial Resistance & Infection Control, 2018

Background: Colistin has been used for therapy of carbapenem-resistant Gram-negative infections in Thailand, especially carbapenem-resistant A. baumannii and P. aeruginosa, for more than 10 years. However, the prevalence of colistin-resistant A. baumannii or P. aeruginosa is still less than 5%. Colistin-resistant Enterobacteriaceae has been increasingly reported globally over the past few years and the use of colistin in food animals might be associated with an emergence of colistin resistance in Enterobacteriaceae. This study aimed to determine the effect of colistin exposure in hospitalized patients who received colistin on development of colistin-resistant (CoR) Escherichia coli (EC) or Klebsiella pneumoniae (KP) colonization and infection. Methods: A prospective observational study was performed in adult hospitalized patients at Siriraj Hospital who received colistin for treatment of infections during December 2016 and November 2017. The surveillance culture samples were collected from the stool and the site of infection of each patient who received colistin at the study enrollment, days 3 and 7 after the study enrollment, and once a week thereafter for determination of CoR EC and CoR KP. CoR EC and CoR KP were also tested for a presence of mcr-1 gene. Results: One hundred thirty-nine patients were included. Overall prevalence of CoR EC or CoR KP colonization was 47.5% among 139 subjects. Prevalence of CoR EC or CoR KP colonization was 17.3% of subjects at study enrollment, and 30.2% after study enrollment. Use of fluoroquinolones, aminoglycosides, and colistin was found to be significantly associated with CoR EC or CoR KP colonization. The mcr-1 gene was detected in 13.0% of CoR EC or CoR KP isolates, and in 27.3% of subjects with CoR EC or CoR KP colonization. CoR EC or CoR KP colonization persisted in 65.2% of the subjects at the end of the study. Five patients with CoR KP infections received combination antibiotics and they were alive at hospital discharge. Conclusions: Prevalence of CoR EC or CoR KP colonization in hospitalized patients receiving colistin was high and it was associated with the use of colistin. Therefore, patients who receive colistin are at risk of developing CoR EC or CoR KP colonization and infection.

The role of colonization pressure in the dissemination of colistin or tigecycline resistant KPC-producing Klebsiella pneumoniae in critically ill patients

Infection, 2014

To identify the risk factors for incident enteric colonization by KPC-producing Klebsiella pneumoniae (KPC-Kp) resistant to colistin or tigecycline during Intensive Care Unit (ICU) stay. A prospective observational study of patients admitted to the ICU was conducted during a 27-month period. Rectal samples taken upon admission and weekly afterwards were inoculated on selective chromogenic agar. K. pneumoniae isolates were characterized by standard methodology. Mean inhibitory concentration (MIC) to colistin and tigecycline were determined by E-test. The presence of bla KPC gene was confirmed by PCR. Among 254 patients, 62 (24.4%) became colonized by colistin- resistant KPC-Kp during their stay. Multivariate analysis revealed that corticosteroid, colistin administration and number of colonized patients in nearby beds per day were significantly associated with colonization. Among 257 patients, 39 (17.9%) became colonized by tigecycline resistant KPC-Kp during their stay. Risk factors ...