Rapid Phenotypic Antibiotic Susceptibility Profiling of Clinical Escherichia coli and Klebsiella pneumoniae Blood Cultures.

Bloodstream infections (BSI) are defined by the presence of viable bacteria or fungi, accompanied by systemic signs of infection. Choosing empirical therapy based solely on patient risk factors and prior antibiotic susceptibility test (AST) may lead to either ineffective treatment or unnecessarily broad-spectrum antibiotic exposure. In general, Clinical & Laboratory Standards Institute guideline-approved ASTs have a turnaround time of 48-72 h from sample to answer, a period that may result in a critical delay in the appropriate selection of therapy. Therefore, reducing the time required for AST is highly advantageous. We have previously shown that our novel rapid AST method, MAPt (Micro-Agar-PCR-test), accurately identifies susceptibility profiles for spiked bioterrorism agents like Bacillus anthracis, Yersinia pestis and Francisella tularensis directly from whole-blood and blood culture samples, even at low bacterial levels (500 CFU/mL). This study evaluated the performance of MAPt on routine bloodstream infection (BSI), focusing on Escherichia coli and Klebsiella pneumoniae isolates from clinical cultures, including resistant strains to some of the six tested antibiotics. Notably, MAPt yielded results exceeding 95% agreement with the standard hospital method within a significantly shorter timeframe of 6 h. These findings suggest significant potential for MAPt as a rapid and reliable BSI management tool.

Real-time PCR for Strongyloides stercoralis-associated meningitis.

Four immunocompromised patients, immigrants from Ethiopia, presented with diverse clinical manifestations of meningitis associated with Strongyloides stercoralis dissemination as determined by identification of intestinal larvae. The cerebrospinal fluid of 3 patients was tested by a validated (for stool) real-time PCR for S. stercoralis and was found positive, establishing this association.

An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.

BACKGROUND: The highly transmissible and virulent carbapenem-resistant Klebsiella pneumoniae (CRKP) KPC-3 strain has been spreading in our medical center and in other centers in Israel since 2006. An intervention that aimed to diminish its prevalence was constructed and applied in our institute. METHODS: We analyzed the efficacy of the intervention during the years 2006-2010 using quasi-experimental methodology. The intervention included guidelines for patient isolation, cohorting, and environment cleaning; education of staff; and a computerized notification system that flags CRKP carriers and provides instructions. The efficacy of the program was evaluated through 3 quantifiable parameters: incidence of CRKP isolates from clinical samples, rate of cross-infections, and rate of screening for CRKP carriage in patients at risk identified by rectal samples. RESULTS: The incidence of CRKP decreased by 16-fold (P < .001), and this decrease was sustained for 30 months. The rate of cross-infection decreased from 6% during 2007-2008 to 2.7% in 2009-2010 (P < .05). This period saw an increased rate of active surveillance for carriers, from 20% to 89%. CONCLUSIONS: A comprehensive infection control program can contain an outbreak of the CRKP KPC-3 strain in acute care hospitals during a nationwide outbreak of this strain.

Pseudomonas aeruginosa bacteremia upon hospital admission: risk factors for mortality and influence of inadequate empirical antimicrobial therapy.

Pseudomonas aeruginosa is an uncommon cause of bacteremia upon hospital admission (UHA) and the chosen empirical antimicrobial therapy may not cover it appropriately. In a multicenter prospective study conducted in Israel, we evaluated risk factors for in-hospital mortality in patients with P. aeruginosa bacteremia UHA and determined the influence of delay in adequate empirical antimicrobial therapy on patients' outcome. Seventy-six adult patients with P. aeruginosa bacteremia within 72 h of hospital admission were included. Demographic, clinical, and treatment data were collected. Microbiological adequacy of empirical therapy was determined. Severe sepsis or septic shock at admission (OR, 21.9; P < 0.001), respiratory or unknown sources of bacteremia (OR, 11.5; P = 0.003), recent hospitalization (OR, 6.2; P = 0.032), and poor functional status (OR, 5.8; P = 0.029) were identified as independent predictors of mortality. Inadequate empirical antimicrobial therapy was marginally associated with increased mortality only among patients who presented with severe sepsis or septic shock (P = 0.051).

National multicenter study of predictors and outcomes of bacteremia upon hospital admission caused by Enterobacteriaceae producing extended-spectrum beta-lactamases.

Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae are pathogens that may lead to a spectrum of clinical syndromes. We aimed to identify predictors and outcomes of ESBL bacteremia upon hospital admission (UHA) in a nationwide prospective study. Thus, a multicenter prospective study was conducted in 10 Israeli hospitals. Adult patients with bacteremia due to Enterobacteriaceae diagnosed within 72 h of hospitalization were included. Patients with ESBL producers (cases) were compared to those with non-ESBL producers (controls), and a 1:1 ratio was attempted in each center. A case-control study to identify predictors and a cohort study to identify outcomes were conducted. Bivariate and multivariate logistic regressions were used for analyses. Overall, 447 patients with bacteremia due to Enterobacteriaceae were recruited: 205 cases and 242 controls. Independent predictors of ESBL were increased age, multiple comorbid conditions, poor functional status, recent contact with health care settings, invasive procedures, and prior receipt of antimicrobial therapy. In addition, patients presenting with septic shock and/or multiorgan failure were more likely to have ESBL infections. Patients with ESBL producers suffered more frequently from a delay in appropriate antimicrobial therapy (odds ratio [OR], 4.7; P, <0.001) and had a higher mortality rate (OR, 3.5; P, <0.001). After controlling for confounding variables, both ESBL production (OR, 2.3; P, 9.1) and a delay in adequate therapy (OR, 0.05; P, 0.001) were significant predictors for mortality and other adverse outcomes. We conclude that among patients with bacteremia due to Enterobacteriaceae UHA, those with ESBL producers tend to be older and chronically ill and to have a delay in effective therapy and severe adverse outcomes. Efforts should be directed to improving the detection of patients with ESBL bacteremia UHA and to providing immediate appropriate therapy.

First national surveillance of susceptibility of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. to antimicrobials in Israel.

In this 1st national surveillance study, the susceptibility pattern of 1011 consecutive isolates of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella spp. isolated from patients hospitalized in Israel hospitals, covering 62.3% of all general hospital beds in the country, was investigated. Proportion of susceptibilities (range among institutions, MIC(50)/MIC(90) in micrograms per milliliter) were to ertapenem 95.0% (88.8-100%, 0.19/0.75), imipenem 98.8% (88.8-100%, 0.25/0.38), meropenem 98.2% (90.0-100%, 0.06/0.19), piperacillin-tazobactam 59.1% (42.6-77.0%, 16/256), ciprofloxacin 17.2% (9.0-24.6%, 32/32), levofloxacin 17.8% (9.0-24.6%, 32/32), amikacin 74.5% (63.8-98.0%, 6/32), and gentamicin 19.3% (12.3-28.5%, 96/256). Coresistance, cross-resistance, and variability between institutions were high. Only carbapenems retain predicted activity against ESBL-producing E. coli and Klebsiella spp. across Israeli hospitals.

Endocarditis caused by extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae: emergence of resistance to ciprofloxacin and piperacillin-tazobactam during treatment despite initial susceptibility.

Three episodes of bacteremia occurred in the course of prosthetic valve endocarditis caused by an extended-spectrum-beta-lactamase (ESBL)-producing Klebsiella pneumoniae strain. The second isolate developed resistance to ciprofloxacin and the third isolate to piperacillin-tazobactam (PIP-TZ) following sequential therapy with each agent. The first isolate was resistant to PIP-TZ only at high inocula, the second isolate acquired increased transcription of the acrA gene, and the third isolate became resistant to PIP-TZ due to loss of beta-lactamase inhibition by TZ. We question if and how PIP-TZ susceptibility should be reported for ESBL-producing Enterobacteriaceae.

Profile and prognosis of febrile elderly patients with bacteremic urinary tract infection.

OBJECTIVE: To describe the profile of elderly patients with bacteremic urinary tract infections (UTI) and correlate clinical and laboratory findings with the outcome in order to identify independent predictors of mortality. METHODS: This retrospective study took place in a large community-based, geriatric hospital and included 191 patients aged 75-105 years with urine and blood cultures simultaneously positive for bacterial organisms. Records were analysed for demographic information, clinical and laboratory data over a 29 month period. Mortality was assessed and was correlated with these findings. RESULTS: Most of the patients (80.1%) had community-acquired infection. Gram-negative organisms accounted for 87.6% of bacterial isolates, with Escherichia coli accounting for 46.1% of cases. Non-Escherichia coli Gram-negative organisms were highly resistant to two common urinary tract antibiotics (gentamicin and ceftriaxone). Patients with chronic urinary catheter had Gram-negative bacteria significantly less sensitive to ciprofloxacin, gentamycin, ampicillin and ceftriaxon than patients without catheter (p<0.05). In-hospital mortality was 33%. Multiple logistic regression analysis revealed that mortality was significantly related to the number of underlying diagnoses (p<0.0203), cognitive status (p<0.0003), length of hospitalization (p<0.0397), low level of serum albumin (p<0.0021), high neutrophil count (p<0.0001) and high level of lactate dehydrogenase (p<0.0351). Fatality was not associated with advanced age in the very old. CONCLUSION: Bacteremic UTI in the elderly has a high mortality rate. In frail elderly patients with age-associated multiple severe underlying disorders and cognitive impairment, early recognition of bacteremic UTI and prompt, appropriate treatment are critical in reducing the mortality.

Human parvovirus B19 infection in children: uncommon clinical presentations.

BACKGROUND: Human parvovirus B19 is responsible for a variety of clinical syndromes, such as erythema infectiosum, non-immune hydrops fetalis, transient aplastic anemia, and arthropathies. HPV is also suspected of playing a role in the pathogenesis of various chronic inflammatory and autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, Kawasaki disease and multiple sclerosis. OBJECTIVES: To study the age distribution and clinical presentation of patients hospitalized for human parvovirus B19 infection. METHOD: We reviewed the case records of all pediatric patients with serologic evidence of HPV infection who were admitted during a 20 month period to a major community hospital. RESULTS: Of 128 children tested for HPV, 48 had evidence of acute infection based on the presence of immunoglobulin M antibodies; 8 patients who also had positive IgM for other viruses were excluded, thus 40 case records were studied. The mean age of the patients was 5.21 years, but 22 patients were under 4. The clinical presentations included 25 patients with fever, either recurrent or prolonged, accompanied in some by enlarged spleen, liver and lymph nodes, skin rash and arthropathy; the remaining patients were investigated for anemia, skin rash, joint complaints and hepatitis. In addition, HPV infection was documented in several well-defined clinical conditions, such as SLE, vasculitic skin lesions, acute lymphoblastic leukemia, pure red cell aplasia, and optic neuritis. CONCLUSIONS: In a group of 40 pediatric patients exhibiting anti-HPV IgM antibodies, a younger age and less common clinical presentations were observed, furthermore 5 patients had clinical syndromes in which the causative role of HPV infection was not clear.