Abstract
Background
Carbapenem-resistant Klebsiella pneumoniae (CRKp) have become an increasing public health problem worldwide. While most CRKp around the world harbour a carbapenemase enzyme, the ...clinical relevance of non-carbapenemase-producing CRKp (non-CP-CRKp) is increasingly recognized. Selective digestive decontamination (SDD) has been proven successful as a decolonization strategy for patients colonized with Gram-negatives in the ICU. However, it is not regularly used to treat invasive infections.
Objectives
To report the use of SDD as a useful strategy for managing recalcitrant CRKp bloodstream infections.
Patients and methods
We present a neutropenic patient with a recalcitrant bloodstream infection with non-CP-CRKp treated with SDD. Besides, genomic analyses of five isolates of non-CP-CRKp was performed.
Results
After 11 days of SDD treatment with oral colistin and gentamicin, bacteraemia was successfully eradicated. Genomic analysis indicates a fully carbapenem-resistant phenotype evolved in vivo and suggests that the mechanism of carbapenem resistance in our strains relates to gene amplification of narrow-spectrum β-lactamases.
Conclusions
Our report highlights that SDD might be a useful strategy to manage CRKp bloodstream infections, when intestinal translocation is the likely source of the bacteraemia. In addition, the development of a resistant phenotype during therapy is worrisome as therapies directed against these organisms are likely to favour the amplification process.
To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a ...multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006−2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy IEAT on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain 38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 95%CI 1.01−2.03; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 95%CI 0.27−0.78; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 95%CI 0.76−2.05; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.
Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors ...(ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006–May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 10sup.9 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.
Introduction Pseudomonas aeruginosa (PA) has historically been one of the major causes of severe sepsis and death among neutropenic cancer patients. There has been a recent increase of ...multidrug-resistant PA (MDRPA) isolates that may determine a worse prognosis, particularly in immunosuppressed patients. The aim of this study is to establish the impact of antibiotic resistance on the outcome of neutropenic onco-haematological patients with PA bacteraemia, and to identify the risk factors for MDRPA bacteraemia and mortality.Methods and analysisThis is a retrospective, observational, multicentre, international study. All episodes of PA bacteraemia occurring in neutropenic onco-haematological patients followed up at the participating centres from 1 January 2006 to 31 May 2018 will be retrospectively reviewed. The primary end point will be overall case-fatality rate within 30 days of onset of PA bacteraemia. The secondary end points will be to describe the following: the incidence and risk factors for multidrug-resistant and extremely drug-resistant PA bacteraemia (by comparing the episodes due to susceptible PA with those produced by MDRPA), the efficacy of ceftolozane/tazobactam, the rates of persistent bacteraemia and bacteraemia relapse and the risk factors for very early (48 hours), early (7 days) and overall (30 days) case-fatality rates.Ethics and disseminationThe Clinical Research Ethics Committee of Bellvitge University Hospital approved the protocol of the study at the primary site. To protect personal privacy, identifying information of each patient in the electronic database will be encrypted. The processing of the patients’ personal data collected in the study will comply with the Spanish Data Protection Act of 1998 and with the European Directive on the privacy of data. All data collected, stored and processed will be anonymised. Results will be reported at conferences and in peer-reviewed publications.
Resumen Las quinolonas constituyen una familia de antimicrobianos de amplio uso y si bien son consideradas segura para los pacientes, el conocimiento del perfil de seguridad es necesario para que los ...profesionales estén alertas a lo que deben vigilar. Sobre el sistema músculo-esquelético, las quinolonas tienen el potencial de dañar cartílagos, provocando incluso muy excepcionalmente rotura de tendón. A nivel endocrino se ha observado hipoglicemia/hiperglicemia, por lo que en pacientes diabéticos se recomienda el control cuidadoso de la glicemia. Las reacciones adversas cardiovasculares son poco frecuentes, pero pueden ir desde alteraciones del ECG como prolongación del QT sin traducción clínica a graves arritmias que pueden ser de riesgo vital. En el sistema nervioso, destaca la aparición de alteraciones del sistema nervioso central y la neuropatía periférica. Durante la evaluación de la seguridad de las quinolonas es importante considerar las potenciales interacciones con otros medicamentos. En niños se prefiere no usar las fluoroquinolonas debido al potencial riesgo de daño a los cartílagos de crecimiento, efectos que no parecen ser tan dramáticos a la luz de la evidencia actual. A pesar del optimismo se debe evaluar la seguridad del tratamiento de estos antimicrobianos en todo paciente pediátrico.
Abstract
Background
Carbapenem-resistant Enterobacteriaceae (CRE) are a critical global health problem. We detected a surge of CRE cases in a pediatric hospital in Chile, a country with a low ...endemicity of KPC-producing organisms. Herein, we describe the molecular epidemiology of this outbreak.
Methods
CRE isolates from clinical specimens and surveillance rectal swabs (obtained using chromID CARBA SMART agar, BioMerieux) of pediatric patients were collected from July 2015 to January 2017. Species identity was confirmed by MALDI-TOF. Carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48-like) were detected by multiplex PCR, followed by amplification and sequencing of the blaKPC allele. Conjugation experiments were conducted with representative species as donors and sodium azide-resistant E. coli J53 as recipient. PCR-based plasmid typing (PBRT Diatheva kit) was then performed on donors and recipients. For K. pneumoniae, genetic relatedness was investigated by PFGE, multilocus sequence typing and wzi typing.
Results
Sixty-one CRE clinical and surveillance isolates were obtained from 49 patients aged 17 days to 16 years. blaKPC-2 was present in 57/62 isolates; no other carbapenemases were found. For 11 patients, multiple cultures were obtained; 4/11 had more than one KPC-harboring species. KPC-harboring isolates displayed ertapenem MICs ranging from 1 to >8 mg/L. Preliminary analyses suggest that blaKPC-2 is contained within a nonclassical Tn4401 structure (lacking the upstream promoter). Mating experiments indicate that blaKPC-2 is carried by a conjugative IncN backbone plasmid. Interestingly, K. pneumoniae isolates were nonclonal by PFGE and belonged to multiple STs unrelated to CG258 (ST34, ST36, among others) and different wzi types (37, 154, among others).
Conclusion
We report a multispecies outbreak of KPC-2 producing CRE in children mainly driven by horizontal dissemination of a promiscuous IncN plasmid. The nonclonal, multispecies nature of this outbreak provides insights into the complex dynamics of KPC dissemination in countries like Chile, where the clonal spread of highly successful clones like CG258 is not the predominant dissemination vehicle, and instead HGT-related spread could be playing a more important role.
Disclosures
All authors: No reported disclosures.
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