Bloodstream Infections Caused By Klebsiella Pneumoniae in Onco-Hematological Patients: Incidence and Clinical Impact of Carbapenem Resistance in a Multicentre Prospective Survey

Luo

Antimicrob Resist Infect Control

et al. 2020

Background: A consensus has been reached that carbapenem-resistant Enterobacteriaceae (CRE) screening in immunosuppressed individuals can reduce the incidence of CRE bloodstream infection (BSI). Methods:We retrospectively studied the clinical data of 395 consecutive HSCT patients from (period 2), 195 patients received continuous weekly CRE screening after admission. For patients colonized with CRE, targeted managements were received: (1) contact precautions and (2) preemptive CRE-targeted treatment if necessary. Results: During period 1, 3 patients with CRE colonization were detected (1.5%). The CRE BSI rate was 2.0% (4 patients), and the related 30-day mortality was 50.0% (2 out of 4 patients). During period 2, 21 patients with CRE colonization were detected, and the detection rate was significantly higher than that in period 1 (P < 0.001). Of the 21 colonized patients, 4 (19.0%) patients were identified as positive for CRE at the first screening, 5 (23.8%) were identified at the second screening, and the remaining 12 (57.1%) were identified at the third or later screening. The CRE BSI rate decreased to 0.5% (1/195), and there were no CRE-related death. Fifteen colonized patients developed neutropenic fever. Thirteen colonizers were preemptively treated with tigecycline within 24 h of fever onset, and they achieved rapid temperature control. One colonizer received tigecycline later than 48 h after fever onset and ultimately survived due to the addition of polymyxin. The other received tigecycline later than 72 h after fever onset and died of septic shock. Conclusion:The increase in screening frequency contributed to the detection of patients with CRE colonization. Targeted managements for these colonized patients may contribute to reducing the incidence and mortality of CRE BSI, therefore improving the prognosis of patients.

Section: Discussionmentioning

confidence: 99%

Different screening frequencies of carbapenem-resistant Enterobacteriaceae in patients undergoing hematopoietic stem cell transplantation: which one is better?

Luo

Antimicrob Resist Infect Control

et al. 2020

“…NOSO-502 is active against Enterobacteriaceae , including CRE belonging to all classes of the Ambler classification and resistant to gentamicin, polymyxin B, or tigecycline. This is crucial, because these antibiotics, classically used for the treatment of such infections, are associated with high levels of resistance ranging from 9.7 to 51.3% (mean 22.6%) for colistin, 5.6 to 85.4% (mean 43.5%) for gentamicin, and 0 to 33% (mean 15.2%) for tigecycline (8, 9, 10, 11, 12, 13, 14, 15, 16, 17). Current options to address these resistance issues are not entirely satisfactory, because none of the recently approved antibiotics or those under development are effective against all CRE.…”

Section: Discussionmentioning

confidence: 99%

In vitro and In vivo characterization of NOSO-502, a novel inhibitor of bacterial translation

Racine¹,

Nordmann

Pantel³

et al. 2018

Preprint

21Antibacterial activity screening of a collection of Xenorhabdus strains led to the discovery of the 22 Odilorhabdins, a novel antibiotic class with broad-spectrum activity against Gram-positive and 23 Gram-negative pathogens. Odilorhabdins inhibit bacterial translation by a novel mechanism of 24 action on ribosomes. A lead-optimization program identified NOSO-502 as a promising 25 candidate. NOSO-502 has MIC values ranging from 0.5 to 4 µg/ml against standard 26 Enterobacteriaceae strains and carbapenem-resistant Enterobacteriaceae (CRE) isolates that 27 produce KPC, AmpC, or OXA enzymes and metallo-β-lactamases. In addition, this compound 28 overcomes multiple chromosome-encoded or plasmid-mediated resistance mechanisms of 29 acquired resistance to colistin. It is effective in mouse systemic infection models against E. coli 30 EN122 (ESBL) or E. coli ATCC BAA-2469 (NDM-1), achieving an ED50 of 3.5 mg/kg and 1-, 2-and 31 3-log reductions in blood burden at 2.6, 3.8, and 5.9 mg/kg, respectively, in the first model and 32 100% survival in the second, starting with a dose as low as 4 mg/kg. In a UTI model of E. coli 33 UTI89, urine, bladder and kidney burdens were reduced by 2.39, 1.96, and 1.36 log10 CFU/ml, 34 respectively, after injecting 24 mg/kg. There was no cytotoxicity against HepG2, HK-2, or HRPT 35 cells, no inhibition of hERG-CHO or Nav 1.5 -HEK current, and no increase of micronuclei at 512 36 µM. NOSO-502, a compound with a novel mechanism of action, is active against 37 Enterobacteriaceae, including all classes of CRE, has a low potential for resistance development, 38 shows efficacy in several mouse models, and has a favorable in vitro safety profile. 39 40 41 42 43 48 threat level: carbapenem-resistant Enterobacteriaceae (CRE) and Clostridium difficile (1). 49 Carbapenems are broad-spectrum -lactam antibiotics saved for the treatment of the most 50 serious infections. CRE have become resistant to all or nearly all antibiotics available and cause 51 many types of serious infection, such as those of the respiratory tract, urinary tract, abdomen 52 and bacteremia (2). The CDC estimates that 9,300 healthcare-associated infections are caused 53 each year in the United States by the two most common types of CRE, carbapenem-resistant 54Klebsiella species and Escherichia coli species, causing approximately 600 deaths (1). In China, 55 among the 664 CRE cases reported in 2015 in 25 hospitals, most were caused by K. pneumoniae 56 (73.3%), E. coli (16.6%), or E. cloacae (7.1%) and the overall mortality rate was 33.5% (2). 57 Antibacterial activity screening of a collection of Xenorhabdus strains led to the discovery of the 58 Odilorhabdins, a novel antibiotic class with broad-spectrum activity against Gram-positive and 59 Gram-negative pathogens (3). Odilorhabdins inhibit bacterial translation by a novel mechanism 60 of action on ribosomes (3). Their chemical tractability made them suitable for a lead optimization 61 program by medicinal chemistry that led to the preclinical can...

Transplant Infectious Dis

“…Although the global threat of CRE has been well documented, the emergence of CRE in patients with hematologic malignancies and HSCT recipients has only recently been described . Publications reporting at least 10 HSCT recipients with CRE infection are outlined in Table . Carbapenem‐resistant K. pneumoniae (CRKP) has become a major cause of bacteremia in this patient population in Italy.…”

Section: Carbapenem‐resistant Enterobacteriaceae (Cre)mentioning

confidence: 99%

“…Carbapenem‐resistant K. pneumoniae (CRKP) has become a major cause of bacteremia in this patient population in Italy. In a prospective cohort study of 13 Italian hematologic oncology centers from 2010 to 2014, 161 (58%) of 278 episodes of K. pneumoniae bloodstream isolates were carbapenem‐resistant . In a study of 52 Italian HSCT centers, the overall incidence of post‐transplant CRKP infection from 2010 to 2013 was 0.4% after an autologous transplant and 2% after an allogeneic transplant .…”

Section: Carbapenem‐resistant Enterobacteriaceae (Cre)mentioning

confidence: 99%

“…In fact, both overall and CRE bacteremia‐related mortality rates in patients with hematologic malignancies and HSCT recipients are consistently >50% (Table ). Trecarichi et al found that the 21‐day mortality rate in patients with hematologic malignancies was 53% after CRKP bacteremia, compared to 15% after carbapenem‐susceptible K. pneumoniae bacteremia, and carbapenem resistance was independently associated with mortality. A CRKP infection‐related mortality rate of 64% was reported in allogeneic HSCT (allo‐HSCT) recipients …”

Section: Carbapenem‐resistant Enterobacteriaceae (Cre)mentioning

confidence: 99%

See 1 more Smart Citation

Multidrug‐resistant Enterobacteriaceae, Pseudomonas aeruginosa, and vancomycin‐resistant Enterococcus: Three major threats to hematopoietic stem cell transplant recipients

Satlin

Walsh

2017

Hematopoietic stem cell transplant (HSCT) recipients are uniquely threatened by the emergence of multidrug-resistant (MDR) bacteria because these patients rely on immediate active antimicrobial therapy to combat bacterial infections. This review describes the epidemiology and treatment considerations for three challenging MDR bacterial pathogens in HSCT recipients: MDR Enterobacteriaceae, including extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus (VRE). These bacteria are common causes of infection in this population and bacteremias caused by these organisms are associated with high mortality rates. Carbapenems remain the treatments of choice for serious infections due to ESBL-producing Enterobacteriaceae in HSCT recipients. Administration of β-lactam agents as an extended infusion is associated with improved outcomes in patients with severe infections caused by P. aeruginosa. Older agents used for the treatment of CRE and MDR P. aeruginosa infections, such as polymyxins and aminoglycosides, have major limitations. Newer agents, such as ceftazidime-avibactam and ceftolozane-tazobactam have great potential for the treatment of Klebsiella pneumoniae carbapemenase-producing CRE and MDR P. aeruginosa, respectively, but more pre-clinical and clinical data are needed to better evaluate their efficacy. Daptomycin dosages ≥ 8 mg/kg/day are recommended to treat VRE infections in this population, particularly in the setting of increasing daptomycin resistance. Strategies to prevent these infections include strict adherence to recommended infection control practices and multidisciplinary antimicrobial stewardship. Lastly, gastrointestinal screening to guide empirical therapy and the use of polymerase chain reaction-based rapid diagnostics may decrease the time to administration of appropriate therapy for these infections, thereby leading to improved outcomes.