Identification of the first imported KPC-3 Klebsiella pneumoniae from the USA to Taiwan.

Establishment of KPC-associated genes into a new region usually requires travellers with hospital admission and their carriage into the communities. In this report, a worldwide spreading clone carrying KPC-3 was isolated from the sputum of a hospitalised patient with a serious infection who had just come from the USA and had been admitted to a New York hospital. By genetic comparison with a strain isolated from New Jersey (NJ-KPC-21), this isolate from the traveller was genetically related. The blaKPC-3 gene was harboured on a large plasmid with a complex structure of a Tn3-based transposon, Tn4401a. The KPC-3-carrying plasmid was very similar (>99.9% identity) to the 113 637-bp blaKPC-3-encoding plasmid pKpQIL that originated from the 2006 epidemic carbapenem-resistant Klebsiella pneumoniae outbreak in Israel. With the first recognition of KPC-2 in 2011 and continuing spread, physicians should be aware of the coming of KPC-3 K. pneumoniae in Taiwan.

Plasmid transferability of KPC into a virulent K2 serotype Klebsiella pneumoniae.

BACKGROUND: KPC-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with high mortality; however, their virulence determinants are not well defined. METHODS: We investigated the virulence and plasmid transferability among KPC-containing K. pneumoniae isolates. RESULTS: KPC-2 and -3 were successfully conjugated and retained by a virulent K2 K. pneumoniae recipient isolate. Antimicrobial susceptibility testing showed KPC-2 and -3 donor strains were resistant to more than four classes of antibiotics while the K2 isolate was only initially resistant to ampicillin. After conjugation of KPC-2 and -3, the K2 K. pneumoniae transconjugants became resistant to all beta-lactams. Additionally, the KPC K2 K. pneumoniae transconjugants continued to retain its high serum resistance and murine lethality. CONCLUSIONS: Conjugation and retainment of KPC by virulent K2 K. pneumoniae and the ability of the tranconjugants to maintain its high serum resistance and murine lethality after conjugation was demonstrated in this study. These findings are concerning for the potential of KPC-like genes to disseminate among virulent K. pneumoniae isolates.

Refractory Clostridium difficile Infection Successfully Treated with Tigecycline, Rifaximin, and Vancomycin.

The occurrence of Clostridium difficile colitis is on the rise and has become more difficult to manage with standard therapy. Thus, the need for alternative treatments is essential. Tigecycline is a glycylcycline antibiotic that has been shown to be effective against C. difficile through several published case reports and in in vitro studies. We present a case of C. difficile colitis that failed to respond to metronidazole and oral vancomycin therapy, but improved on a combination of rifaximin, tigecycline, and vancomycin.

Virulence and plasmid transferability of KPC Klebsiella pneumoniae at the Veterans Affairs Healthcare System of New Jersey.

Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae infections are associated with high mortality; however, little is known about the virulence determinants of KPC-producing K. pneumoniae. At the Veterans Affairs New Jersey Healthcare System (VA NJHCS), we investigated the virulence and plasmid transferability of 60 clinically unique KPC-containing K. pneumoniae isolates. All 60 isolates were negative for known virulence factors K1, K2, and K5 capsular antigens; rmpA; and the aerobactin gene by polymerase chain reaction. Isolates varied in their susceptibility to neutrophil phagocytosis, but were less resistant than the virulent serotype K1 isolate. Additionally, no deaths were seen on murine lethality studies. Conjugation results of this study showed that the bla(KPC) gene can be transferred into an Escherichia coli J-53 strain but not to E. coli JP-995. However, the stability is very limited as E. coli J-53 does not retain bla(KPC)-containing plasmids for any period of time. The lack of virulence factors in the set of KPC-producing K. pneumoniae studied suggests that morbidity and mortality may be due to detection issues or lack of effective antibiotics.

Polymyxin Combination Therapy and the Use of Serum Bactericidal Titers in the Management of KPC-Producing Klebsiella pneumoniae Infections: A Report of 3 Cases.

Management of patients with KPC-harboring Enterobacteriaceae has become a significant and challenging scenario. We report three cases of KPC-producing Klebsiella pneumoniae bacteremia that were successfully treated using combination therapy with polymyxin B and other antimicrobials. Serum bactericidal titers were determined and provided additional clinical guidance in the management of such patients.

Phenotypic and genotypic screening and clonal analysis of carbapenem-resistant Klebsiella pneumoniae at a single hospital.

Detection of bla(KPC)-harboring Klebsiella pneumoniae (KP) in the clinical laboratory remains a difficult task. Decreased ertapenem (ERT) susceptibility has been considered one of the most sensitive phenotypic indicators of K. pneumoniae carbapenemase (KPC) production, but has been found to be nonspecific. Susceptibility testing using imipenem or meropenem lacks the sensitivity for detection of KPCs, and there is limited experience using doripenem (DOR). Fifty-five individual ERT-nonsusceptible KP isolates and 19 isolates that were ERT-susceptible, extended spectrum ß-lactamase-positive KP were collected from the clinical laboratory and tested for DOR susceptibility by Etest methodology. PCR screening for bla(KPC) was performed on all specimens. All but three isolates with ERT resistance were KPC positive by PCR. Compared to PCR, ERT detection of KPC had a sensitivity of 98% and a false-positive rate of 6%. Overall, there was a 97% agreement between ERT and DOR susceptibility results. However, there was one KPC-positive isolate that was discrepant (ERT susceptible, DOR nonsusceptible by Etest). Selected isolates of KP from both groups underwent pulsed-field gel electrophoresis analysis to determine the degree of genetic relatedness of KPC-positive and KPC-negative isolates. Pulsed-field gel electrophoresis of selected KPC-positive and KPC-negative KP identified a common pattern between both groups. The resistance to DOR and/or ERT is sensitive and a specific indicator for detection of bla(KPC) in KP.

K2 serotype Klebsiella pneumoniae causing a liver abscess associated with infective endocarditis.

Klebsiella pneumoniae primary liver abscess (KPLA) is an emerging disease that is associated with distant septic complications. We report the first case of KPLA associated with infective endocarditis. The K. pneumoniae strain was a hypermucoid K2 serotype carrying the rmpA virulence-associated gene.

Impact of adding maraviroc to antiretroviral regimens in patients with full viral suppression but impaired CD4 recovery.

We reviewed the effect of adding maraviroc on CD4 cell counts in nine patients on antiretroviral therapy with full viral suppression but impaired CD4 cell recovery. There were no significant differences in changes in CD4 cell count, percentage of CD4 cells, or in the ratio of CD4/CD8 cells at 30 days and 25 weeks of maraviroc therapy. Plasma endotoxin levels measured in four patients before and during maraviroc treatment also showed no significant differences.

The prevalence and virulence characteristics of enteroaggregative Escherichia coli at an urgent-care clinic in the USA: a case-control study.

This case-control study examined the prevalence of enteroaggregative Escherichia coli (EAEC), its genes and elicited inflammatory response, and the stool characteristics of adult patients with and without acute diarrhoeal illness presenting to an urgent-care clinic in the USA. A total of 1004 individual stool specimens (253 from patients with acute diarrhoeal illness and 751 from patients without diarrhoeal illness) were collected between 1 June 2003 and 30 June 2008. EAEC was identified as the sole cause of acute diarrhoeal illness in 6 % (n=15) of patients and in 2 % (n=15) without diarrhoeal illness. Control patients (n=15) were similar to case patients (n=15) for age, gender and co-morbidities. The EAEC genes aggR, aap, aat, astA and/or set1A were identified more frequently in case patients compared with control patients (P <0.05). aggR-positive EAEC elicited higher levels of interleukin (IL)-1ra, IL-6, IL-8 and tumour necrosis factor-alpha compared with aggR-negative EAEC during co-incubation with HCT-8 cells. Patients with EAEC diarrhoea and isolates with the genes aggR, aap, aatA, astA or set1A had stools characterized by gross mucus and the presence of faecal leukocytes (P <0.05). These results indicate that EAEC is a potential cause of acute diarrhoeal illness affecting patients presenting to an acute-care clinic in the USA and suggest that aggR, aap, aatA, astA and set1A may be markers for virulence.

Prosthetic Joint Infection due to Mycobacterium bovis after Intravesical Instillation of Bacillus Calmette-Guerin (BCG).

Intravesical instillation of Bacillus Calmette-Guerin (BCG) is a treatment to prevent recurrence of superficial urothelial bladder carcinoma. Complications after bladder instillation of BCG have been reported including locally invasive and systemic infections due to dissemination of Mycobacterium bovis from the bladder. We present an uncommon case and literature review of prosthetic joint infection due to M. bovis after intravesical BCG treatment of bladder cancer.

Identification of carbapenem-resistant klebsiella pneumoniae harboring KPC enzymes in New Jersey.

Klebsiella pneumoniae isolates harboring KPC enzymes have been identified in many geographical areas since 2001. Numerous problems exist in the detection and treatment of patients with such isolates. The clinical characteristics and molecular epidemiology associated with 12 randomly chosen patients in whom these enzymes were detected by molecular methods are described. This is the first description of the identification of carbapenem-resistant K. pneumoniae isolates harboring KPC beta-lactamases at the Veterans Administration Hospital in New Jersey (VA NJHCS). Because recognition of carbapenem resistance in K. pneumoniae due to KPC enzymes can only be achieved by molecular methods, detection in the Clinical Microbiology Laboratory by routine methods will continue to be difficult, leading to dilemmas in treatment.

A review of an emerging enteric pathogen: enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAEC) is an increasingly recognized enteric pathogen. It is a cause of both acute and persistent diarrhoea among children, adults and HIV-infected persons, in both developing and developed countries. In challenge studies, EAEC has caused diarrhoeal illness with the ingestion of 10(10) c.f.u. Outbreaks of diarrhoeal illness due to EAEC have been reported, and linked to the ingestion of contaminated food. Diarrhoeal illness due to EAEC is the result of a complex pathogen-host interaction. Some infections due to EAEC result in diarrhoeal illness and elicit an inflammatory response, whereas other infections do not result in a symptomatic infection. Many putative virulence genes and EAEC strains that produce biofilm have been identified; however, the clinical significance of these genes and of biofilm production has yet to be defined. A -251 AA single nucleotide polymorphism (SNP) in the interleukin (IL)-8 promoter region is reported to increase host susceptibility to EAEC diarrhoea. Ciprofloxacin and rifaximin continue to be an effective treatment in persons infected with EAEC. This review is intended to provide an updated review for healthcare workers on EAEC, an emerging enteric pathogen.

Enteroaggregative Escherichia coli is a cause of acute diarrheal illness: a meta-analysis.

BACKGROUND: Conflicting studies exist regarding the role of enteroaggregative Escherichia coli (EAEC) as a cause of acute diarrheal illness. The objective of this meta-analysis was to determine whether identification of EAEC in stool samples is associated with acute diarrheal illness among different subpopulations, by geographic area. METHODS: A comprehensive search of electronic bibliographic databases (Medline and PubMed) from August 1985 to January 2006, as well as a search of conference proceedings, references of articles, and contacts with investigators of EAEC, yielded 354 studies. RESULTS: Forty-one studies (12%) that met the selection criteria (i.e., that examined the association between acute diarrheal illness and the excretion of EAEC among different subpopulations) were included. In this meta-analysis, presence of EAEC identified with the HEp-2 cell adherence assay was found to be significantly associated with acute diarrheal illness among children residing in developing regions (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.36-1.83) and industrialized regions (OR, 1.23; 95% CI, 1.03-1.48), adults with human immunodeficiency virus infection residing in developing regions (OR, 6.43; 95% CI, 2.91-14.16), adults residing in developing regions (OR, 7.15; 95% CI, 1.96-26.04), and international travelers to developing regions (OR, 6.72; 95% CI, 2.62-17.20). A limited number of studies were available that examined the role of EAEC identified by its virulence genes by a DNA probe. CONCLUSIONS: On the basis of this meta-analysis, we conclude that EAEC is a cause of acute diarrheal illness among many different subpopulations in both developing and industrialized regions, that EAEC strains are very heterogeneous and that additional studies that examine the role of EAEC in acute diarrheal illness are needed.

Increased mortality associated with a clonal outbreak of ceftazidime-resistant Klebsiella pneumoniae: a case-control study.

OBJECTIVES: To determine risk factors for ceftazidime-resistant Klebsiella pneumoniae infection and the effect of ceftazidime-resistant K. pneumoniae infection on mortality during an isolated outbreak. DESIGN: Case-control investigation using clinical and molecular epidemiology and prospective analysis of infection control interventions. SETTING: Surgical intensive care unit of a university-affiliated community hospital. PATIENTS: Fourteen case-patients infected with ceftazidime-resistant K. pneumoniae and 14 control-patients. RESULTS: Ten of 14 case-patients had identical strains by pulsed-field gel electrophoresis. Broad-spectrum antibiotic therapy before admission to the unit was strongly predictive of subsequent ceftazidime-resistant K. pneumoniae infection. In addition, patients with ceftazidime-resistant K. pneumoniae infection experienced increased mortality (odds ratio, 3.77). CONCLUSIONS: Cephalosporin restriction has been shown to decrease the incidence of nosocomial ceftazidime-resistant K. pneumoniae. However, isolated clonal outbreaks may occur due to lapses in infection control practices. Reinstatement of strict handwashing, thorough environmental cleaning, and repeat education led to termination of the outbreak. A distinct correlation between ceftazidime-resistant K. pneumoniae infection and mortality supports the important influence of antibiotic resistance on the outcome of serious bacterial infections.