Management of KPC-producing Klebsiella pneumoniae infections

BackgroundKlebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas.AimsTo provide practical suggestion for physicians dealing with the management of KPC-KP infections in critically ill patients, based on expert opinions.SourcesPubMed search for relevant publications related to the management of KPC-KP infections.ContentsA panel of experts developed a list of 12 questions to be addressed. In view of the current lack of high-level evidence, they were asked to provide answers on the bases of their knowledge and experience in the field. The panel identified several key aspects to be addressed when dealing with KPC-KP in critically ill patients (preventing colonization in the patient, preventing infection in the colonized patient and colonization of his or her contacts, reducing mortality in the infected patient by rapidly diagnosing the causative agent and promptly adopting the best therapeutic strategy) and provided related suggestions that were based on the available observational literature and the experience of panel members.ImplicationsDiagnostic technologies could speed up the diagnosis of KPC-KP infections. Combination treatment should be preferred to monotherapy in cases of severe infections. For non–critically ill patients without severe infections, results from randomized clinical trials are needed for ultimately weighing benefits and costs of using combinations rather than monotherapy. Multifaceted infection control interventions are needed to decrease the rates of colonization and cross-transmission of KPC-KP.     

Leptin modulates neutrophil phagocytosis of Klebsiella pneumoniae

Leptin is a pleiotropic hormone-cytokine known to regulate energy homeostasis and immune function. Neutrophils from leptin-deficient mice exhibited impaired phagocytosis of Klebsiella pneumoniae opsonized with serum containing complement and reduced CD11b expression that could be restored with exogenous leptin. These results suggest that leptin is required for normal neutrophil complement-mediated phagocytosis of bacteria.     

产超广谱β-内酰胺酶肺炎克雷伯菌耐药基因分析

目的 了解邢台地区产超广谱β-内酰胺酶(ESBLs)肺炎克雷伯菌的分子流行病学特点,为临床感染预防和治疗提供依据.方法 采用最小抑菌浓度(MIC)法检测产ESBLs肺炎克雷伯菌的耐药性,选取13种特异性引物采用聚合酶链反应(PCR)的方法检测产ESBLs肺炎克雷伯菌的基因类型.结果 2013年1月至2014年3月从邢台人民医院分离出的125株非重复的产ESBLs肺炎克雷伯菌菌株,耐药基因以blaCTX-M的阳性率最高,为92.0％,blaSHV和blaTEM次之,为82.9％和73.2％.所有菌株均携带1种或1种以上的耐药基因.结论 产ESBLs肺炎克雷伯菌多重耐药现象严重,耐药基因以blaCTX-M、blaSHV和blaTEM为主.医院应加强对ESBLs的监测,降低ESBLs的感染率以及耐药基因的突变,提高治疗感染的效率,防止医院感染的发生.     

Plasmid mediated antibiotic resistance in Klebsiella pneumoniae

Klebsiella pneumoniae species (108) isolated from tertiary care hospitalized patients were investigated for antibiotic resistance patter. 74% isolates were from urine, 13.5% from pus, 4.5% from blood and 8% from sputum. The resistance pattern of the organisms to various antibiotics were as follows: ampicillin 93.3%, cefotaxime 70%, ceftazidime 81%, gentamicin 68.5%, amikacin 63.75%, netilmicin 74%, norfloxacin 55%, ofloxacin 53%, chloramphenicol 82%, tetracycline 85%, sulphamethoxazole 96%, trimethoprim 94%. 2-4 drug resistance was found in 34.5%, 5-8 drug resistance was in 25.1% and 9-12 drug resistance was found in 40.4% of strains. Out of 65 strains, 25 strains could be successfully conjugated. Common drugs which were transferred to transconjugants were sulphamethoxazole, trimethoprim, gentamicin, netilmicin, amikacin, chloramphenicol, tetracycline, ampicillin, cefotaxime and ceftazidime. A large plasmid of 98.7% kb could be demonstrated in these strains by alkali denaturation method and agarose gel electrophoresis.     

Epidemiology of Quinolone Resistance of Klebsiella pneumoniae and Klebsiella oxytoca in Europe

 The epidemiology of quinolone resistance and the concomitant resistance to other antibiotic classes was investigated in 445 Klebsiella pneumoniae and 238 Klebsiella oxytoca isolates. Decreased susceptibility to ciprofloxacin was found in 7.2% and 3.4% of these two species, respectively. Ciprofloxacin resistance was significantly linked to ceftazidime resistance, the hallmark of extended-spectrum β-lactamase production, as well as to resistance to all antibiotic classes tested. Using automated ribotyping, seven intrahospital- and interhospital-transmitted clones of ciprofloxacin-resistant isolates were found. The newer fluoroquinolones sitafloxacin and clinafloxacin may become increasingly valuable, since they proved to be active also against ciprofloxacin-resistant isolates.     

Immunological properties of purified Klebsiella pneumoniae heat-stable enterotoxin

Klebsiella pneumoniae heat-stable enterotoxin was purified to apparent homogenicity by the same techniques used to purify Escherichia coli heat-stable enterotoxin. The two toxins had the same potency in the suckling mouse assay and showed immunological cross-reactivity in enzyme-linked immunosorbent assay, neutralization of secretory activity by specific hyperimmune antisera, and protection against active challenge in rats immunized with a vaccine containing synthetically produced E. coli heat-stable enterotoxin.     

Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates

A multilocus sequence typing (MLST) scheme was developed for Klebsiella pneumoniae. Sequences of seven housekeeping genes were obtained for 67 K. pneumoniae strains, including 19 ceftazidime- and ciprofloxacin-resistant isolates. Forty distinct allelic profiles were identified. MLST data were validated against ribotyping and showed high (96%) discriminatory power. The MLST approach provides unambiguous data useful for the epidemiology of K. pneumoniae isolates.     

Cerebritis: An unusual complication of Klebsiella pneumoniae

Cerebritis is part of a continuum of brain infection and is difficult to diagnose. Cerebritis caused by Klebsiella in immunocompetent adults without predisposing factors such as neurosurgery or penetrating brain injury has not been reported before. We report a case of Klebsiella cerebritis in an adult patient with a proven extracranial focus of infection. We suggest considering cerebritis as a differential diagnosis for altered level of consciousness in patients of severe sepsis, even if an extracranial source of infection is proven.     

Klebsiella pneumoniae bacteraemia in a region of Canada

The second case of magA+ rmpA+ hypermucoviscosity phenotype Klebsiella pneumoniae infection was documented in Canada, in an immigrant from Algeria. To ascertain whether this represented recent importation of the strain or local transmission within Canada, a retrospective study of K. pneumoniae bacteraemia was conducted in the region, from 1997 to 2007, and 411 episodes were identified. No epidemiological evidence for local transmission of this strain was found. However, for the first time, the population incidence of K. pneumoniae bacteraemia was determined, which increased by 82% between 1997 and 2007, from 10.2 to 18.7 per 100 000 inhabitants. Incidence increased dramatically with age and with the presence of diabetes, but remained stable over time within each stratum. The proportion of patients with K. pneumoniae bacteraemia who were diabetic increased from 26% (1997–2004) to 42% (2005–2007). The rising incidence of K. pneumoniae bacteraemia may represent an unexpected consequence of the expanding population of adult diabetics.     

Liver abscess caused by Klebsiella pneumoniae in siblings

Klebsiella pneumoniae has been emerging as the leading cause of liver abscess in diabetic patients. Results of molecular typing of K. pneumoniae isolates from two siblings with liver abscess, their family members, and the environment suggest a possibility of cross infection of liver abscess by the fecal-oral route within diabetic patients.     

Outcome of carbapenem resistant Klebsiella pneumoniae bloodstream infections

The aim of this study was to evaluate the impact of carbapenem-resistant K. pneumoniae bloodstream infections on mortality. During the study period 42, 68 and 120 patients were identified with carbapenem-resistant, extended-spectrum b-lactamase producers (ESBL) and susceptible K. pneumoniae bloodstream infections, respectively. Patients with carbapenem-resistant K. pneumoniae had higher rates of prior antimicrobial exposure, other nosocomial infections, and use of invasive devices. Infection-related mortality was 48% for carbapenem-resistant, 22% for ESBL producers and 17% for susceptible K. pneumoniae. Independent risk factors for infection-related mortality were Pitt bacteraemia score, Charlson score and carbapenem resistance.     

l-Proline protects mice challenged by Klebsiella pneumoniae bacteremia

ObjectiveK. pneumoniae, a common pathogen that frequently causes bacteremia in clinic, is unresponsive to most of known antibiotics, thus cumulatively exacerbating empirical therapy failures. Effective strategies to control Klebsiella pneumoniae bacteremia are in high demand. One possibility is to mobilize host defense mechanisms against bacterial pathogens.MethodsWe employed GC/MS-based metabolomics to identify the changes of metabolism in mice challenged by K. pneumoniae (ATCC 43816) bacteremia.ResultsCompared with the mice that compromised from K. pneumoniae bacteremia, mice that survived from infection displayed the varied metabolomic profile. The differential analysis of metabolome showed that Ethanedioic acid, d-Glucose, l-Glutamine, Myo-inositol, and l-Proline were more likely associated with the host surviving a K. pneumoniae bacteremia. Further pathway enrichment analysis proposed that arginine and proline metabolism involved in outcome of K. pneumoniae bacteremia. The follow-up data showed that exogenous l-Proline but not d-Proline could decline the loads of Klebsiella pneumonia in infected blood and tissues (lung, liver and spleen) and increase the mouse survival.ConclusionOur study provides an exercisable strategy of identifying metabolic biomarkers from surviving host and highlights the possibility of utilizing the metabolic biomarker as a therapy for K. pneumoniae bacteremia.     

Selective medium for isolation of Klebsiella pneumoniae.

Selective media for Klebsiella pneumoniae have been important in studies of hospital-acquired infections. On an agar medium which included ornithine, raffinose, and Koser citrate, K. pneumoniae strains grew as yellow mucoid colonies at 24 h and there was some increase in colony size at 48 h. Other members of Enterobacteriaceae were inhibited or produced small pink colonies on this same medium. Pseudomonas, Providencia, Acinetobacter, and Proteus species did not grow or showed very poor growth. The growth and appearance of these bacteria were not influenced by pH changes over a pH range of 5.2 to 6.4. Of 368 swabs of body sites cultured on MacConkey agar and on the test medium, 121 K. pneumoniae isolates on MacConkey agar and the same number on the test medium resulted. There were no discrepancies between the two media. Upon direct plating of stool, however, more K. pneumoniae colonies were isolated on the test medium than on MacConkey agar. Colonies on the test medium were more readily selected and identified than the colonies on MacConkey agar. There was also no inhibition of K. pneumoniae growth on the test medium compared with blood agar medium. This medium may be useful for the selective isolation of K. pneumoniae.     

IMP-producing carbapenem-resistant Klebsiella pneumoniae in the United States

The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) producing acquired carbapenemases have created a global public health crisis. In the United States, CRE producing the Klebsiella pneumoniae carbapenemase (KPC) are increasingly common and are endemic in some regions. Metallo-β-lactamase (MBL)-producing CRE have recently been reported in the United States among patients who received medical care in countries where such organisms are common. Here, we describe three carbapenem-resistant K. pneumoniae isolates recovered from pediatric patients at a single U.S. health care facility, none of whom had a history of international travel. The isolates were resistant to carbapenems but susceptible to aztreonam, trimethoprim-sulfamethoxazole, and fluoroquinolones. The three isolates were closely related to each other by pulsed-field gel electrophoresis and contained a common plasmid. PCR and sequence analysis confirmed that these isolates produce IMP-4, an MBL carbapenemase not previously published as present among Enterobacteriaceae in the United States.