Management of KPC-Producing Klebsiella pneumoniae Infections

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III

New perspectives in the antibiotic treatment of mechanically ventilated patients with infections from Gram-negatives

Introduction: Ventilator-associated pneumonia (VAP) is a common and potentially fatal complication of mechanical ventilation that is often caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB). Despite the repurposing of older treatments and the novel antimicrobials, many resistance mechanisms cannot be confronted, and novel therapies are needed. Areas covered: We searched the literature for keywords regarding the treatment of GNB infections in mechanically ventilated patients. This narrative review presents new data on antibiotics and non-antibiotic approaches focusing on Phase 3 trials against clinically significant GNB that cause VAP. Expert opinion: Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam stand out as new options for infections by Klebsiella pneumoniae carbapenemase-producing bacteria, whereas ceftolozane-tazobactam adds therapeutic flexibility in Pseudomonas aeruginosa infections with multiple resistance mechanisms. Ceftazidime-avibactam and ceftolozane-tazobactam have relevant literature. Aztreonam-avibactam holds promise for the treatment of infections by metallo-β-lactamase (MBL)-producing organisms. Recently approved cefiderocol possesses an extended antibacterial spectrum, including KPC- and MBL-producers. However, recently published data have toned down optimism about treating VAP caused by carbapenem-resistant Acinetobacter baumannii. For the latter, eravacycline may provide additional hope, pending pertinent data. Non-antibiotic treatments currently being considered as adjunct therapeutic approaches are welcome. Nevertheless, they will hopefully substitute current antimicrobials in the future. © 2020 Informa UK Limited, trading as Taylor & Francis Group

Guidelines on the use of external ventricular drain and its associated complications: do we “AGREE II”?

Insertion of an external ventricular drain is a common procedure used in everyday practice by neurosurgeons all around the world. It consists of the placement of an external ventricular drain (EVD) into the ventricular system providing the ability to measure intracranial pressure, and also divert the flow of cerebrospinal fluid (CSF) in a variety of pathological conditions. The most common complication is infection, and it may result in devastating consequences and negatively affect the outcome of these patients. The Infectious Diseases Society of America (IDSA), the Neurocritical Care Society (NCS), and The Society for Neuroscience in Anesthesiology & Critical Care (SNACC) have published recommendations for the management of EVD-Associated Ventriculitis. The objective of this study was to assess the methodological quality and reporting clarity of these recommendations using the AGREE-II tool. We found that the overall quality of the published clinical practice guidelines is acceptable. However, continuous updates and external validation should be implemented. © 2021 The Neurosurgical Foundation

Intra-Abdominal Hypertension is a Risk Factor for Increased VAP Incidence: A Prospective Cohort Study in the ICU of a Tertiary Hospital

Background: Ventilator-associated pneumonia (VAP) might be increased in cases with intra-abdominal hypertension (IAH). However, despite animal experimentation and physiological studies on humans in favor of this hypothesis, there is no definitive clinical data that IAH is associated with VAP. We therefore aimed to study whether IAH is a risk factor for increased incidence of VAP in critical care patients. This 1-center prospective observational cohort study was conducted in the intensive care unit of the University Hospital of Larissa, Greece, during 2013 to 2015. Consecutive patients were recruited if they presented risk factors for IAH at admission and were evaluated systematically for IAH and VAP for a 28-day period. Results: Forty-five (36.6%) of 123 patients presented IAH and 45 (36.6%) presented VAP; 24 patients presented VAP following IAH. Cox regression analysis showed that VAP was independently associated with IAH (1.06 [1.01-1.11]; P =.053), while there was an indication for an independent association between VAP and abdominal surgery (1.62 [0.87-3.03]; P =.11] and chronic obstructive pulmonary disease (1.79 [0.96-3.37]; P =.06). Conclusions: Intra-abdominal hypertension is an independent risk factor for increased VAP incidence in critically ill patients who present risk factors for IAH at admission to the ICU. © The Author(s) 2018

Risk Factors for the First Episode of Klebsiella pneumoniae Resistant to Carbapenems Infection in Critically Ill Patients: A Prospective Study

Objective. To identify risk factors for the first episode of Klebsiella Pneumonia resistant to carbapenems (KPRC) infection in critically ill patients. Design, Setting, and Methods. This prospective cohort study was conducted in a 12-bed general Intensive Care Unit (ICU) in a University Hospital on ICU patients who required mechanical ventilation (MV) for >48 hours during a 12-month period. Clinical and microbiologic data were studied. Characteristics of KPRC patients were compared with those of critically ill patients who presented nonmultidrug resistant (MDR) bacterial infections or no documented infection at all. Results. Twenty-five patients presented KPRC infection, 18 presented non-MDR bacterial infection, and 39 patients presented no infection. Compared to patients without documented infection or infected by non MDR bacteria, patients with KPRC infection had received more frequently or for longer duration antibiotics against Gram-negative bacteria (carbapenems, colistin P < 0.05). Duration of colistin administration prior to KPRC isolation was independently associated with increased frequency of KPRC infection (odds ratio, 1.156 per day; 95% confidence interval, 1.010 to 1.312; P = 0.025). KPRC patients stayed longer in the ICU and received mechanical ventilation and sedation for longer periods and presented increased mortality (P < 0.05). Conclusion. KPRC infection is an emerging problem which might be more common in patients with previous use of antibiotics and especially colistin

Combined intravenous and intraventricular administration of colistin methanesulfonate in critically ill patients with central nervous system infection

Colistin pharmacokinetics were prospectively studied after intravenous administration of colistin methanesulphonate in critically ill patients without central nervous system infection (controls, n=5) and in patients with external ventricular drain-associated ventriculitis after intravenous administration (EVDViv, n=3) or combined intravenous/intraventricular administration (EVDVcomb, n=4). Cerebrospinal fluid (CSF)/serum colistin concentration ratios were higher in EVDViv than in control patients (11% versus 7%, P≤0.05) and in EVDVcomb compared to all other patients (P&lt;0.0001). CSF colistin concentrations above the MIC of 0.5 μg/ml were achieved only in EVDVcomb patients. Copyright © 2013, American Society for Microbiology. All Rights Reserved

Toll-like receptor 2, 4 and 9 polymorphisms and their association with ICU-acquired infections in Central Greece

Purpose: To test the potential of four common Toll-like receptor (TLR) polymorphisms to predispose to specific intensive care unit (ICU)-acquired infections and affect outcomes in a Greek ICU. Materials and methods: The incidence of TLR2-Arg753Gln, TLR4-Asp299Gly, TLR4-Thr399Ile and TLR9-T1237C polymorphisms, and their association with ICU-acquired infections and patients' clinical outcomes were prospectively evaluated The examined genetic polymorphisms were assessed by real-time Polymerase-Chain-Reaction (PCR). Results: During a 15-month period, 224 patients were enrolled and genotyped. The prevalence of genetic polymorphisms for TLR4-Asp299Gly, TLR4-Thr399Ile, mixed TLR4-Asp299Gly/Thr399Ile, TLR9-T1237C and TLR2-Arg753Gln was 14.4%, 14.7%, 11.2%, 24.5% and 2.2%, respectively. TLR4 polymorphisms were associated with increased susceptibility towards specific ICU-acquired infections, i.e. Gram-negative central-nervous-system infections (CNSI), ventilator-associated pneumonia (VAP) and urinary-tract infections (UTI), principally due to multi-drug resistant (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumonia, respectively (all P < 0.05). TLR9-T1237C polymorphism was associated with lower incidence and fewer relapses of CNSIs and UTIs when compared to mixed TLR4-Asp299Gly/Thr399Ile polymorphism group (P ≤ 0.039). ICU-stay was significantly prolonged in TLR4 polymorphisms (P ≤ 0.0416). Conclusions: Common TLR-signaling polymorphisms might be implicated in the clinical phenotype of ICU-acquired infections in Central Greece. The possible impact of TLR4 polymorphisms on enhanced susceptibility towards Gram-negative MDR-infections in defined critical-disease states warrants further investigation. Trial Registration Clinical Trials.gov identifier: NCT00932243 © 201

Nebulised colistin for ventilator-associated pneumonia prevention

We evaluated whether prophylactic nebulised colistin could reduce ventilator-associated pneumonia (VAP) rates in an intensive care unit (ICU) setting with prevalent multidrug-resistant (MDR) bacteria. We used a single-centre, two-arm, randomised, open-label, controlled trial in a 12-bed ICU in the University Hospital of Larissa, Greece. Patient inclusion criteria included mechanical ventilation of >48 h. The two arms consisted of prophylaxis with 500000 U colistin (Col group) or normal saline (NS group), thrice daily, for the first 10 ICU days or until extubation. The primary outcome of the study was the 30-day VAP incidence. In total, 168 patients entered the study. VAP incidence was not different between Col and NS group patients (14 (16.7%) versus 25 (29.8%), respectively, p=0.07). Regarding the secondary outcomes, the intervention resulted in a lower VAP incidence density rate (11.4 versus 25.6, respectively, p<0.01), and less Gram-negative bacteria-VAP (p=0.03) and MDR-VAP ( p=0.04). Among VAP patients (n=39), prophylaxis with inhaled colistin improved ICU survival (p=0.016). There was no evidence of increased resistance to colistin or multidrug resistance. Our findings suggest that nebulised colistin had no significant effect on VAP incidence. Copyright © ERS 2015

Intraventricular CNS treatment with Colistin-Tigecycline combination: A case series

“Healthcare-associated ventriculitis and meningitis” is a potentially devastating illness following neurosurgical procedures. Multidrug resistant (MDR) and extensively drug resistant (XDR) organisms such as Acinetobacter baumannii and Klebsiella pneumoniae have increasingly been isolated in ventriculitis and meningitis episodes. The treatment of these infections can be challenging, as the antimicrobial options are restricted. Regarding Central Nervous System (CNS) infections the transfer of the antibiotics to the Cerebrospinal Fluid (CSF) is often low which results in decreased drug levels at the infection site. The intraventricular (IVT) administration of antibiotics can be used as an adjunct to the intravenous (IV) treatment of Gram-negative MDR ventriculitis and meningitis, yet pertinent data is scarce. We present the successful management of three cases of healthcare-associated ventriculitis and meningitis due to XDR species with the combined intraventricular administration of colistin and off-label tigecycline, after the initial regimen of colistin given alone through both IVT and IV routes had failed. © 2018 Elsevier Inc