Treatment of Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia: Retrospective Comparison Between Intravenous Colistin and Intravenous Ampicillin-Sulbactam.

Carbapenem-resistant Acinetobacter baumannii has been increasingly reported as the causative agent of ventilator-associated pneumonia (VAP) among patients in the intensive care units. However, there are insufficient data to guide the appropriate treatment for such infection. Our aim was to compare the outcome of carbapenem-resistant A. baumannii VAP treated with colistin or with ampicillin-sulbactam. We conducted a retrospective study of patients diagnosed with carbapenem-resistant A. baumannii VAP during 2008 and 2009. Clinical and microbiologic cure rates, 30-day mortality, and change in renal function were compared between patients treated with colistin versus those treated with ampicillin-sulbactam. The association between treatment and mortality was examined through multivariable logistic regression analysis. Of the 98 patients diagnosed with carbapenem-resistant A. baumannii VAP, 66 were treated with colistin and 32 with ampicillin-sulbactam. Baseline characteristics of patients were similar, except for a longer intensive care unit stay and lower creatinine clearance test before VAP diagnosis among patients treated with colistin. Clinical cure rates were similar in the 2 groups. In the colistin group, microbiologic failure rates were higher at 7 days [16/33 (48%) vs. 3/17 (18%); P = 0.03]; patients had a more significant elevation in creatinine (+0.2 ± 1.0 mg/dL vs. -0.3 ± 1.1 mg/dL; P = 0.021), and treatment was associated with an increased 30-day mortality (adjusted-odds ratio, 6.5; 95% confidence interval, 1.348-31.342; P = 0.02). In conclusion, patients treated with colistin or ampicillin-sulbactam had similar clinical cure rates. However, colistin was associated with higher rates of microbiologic failure, reduction in renal function, and an increased 30-day mortality. A prospective study comparing high-dose colistin and ampicillin-sulbactam for the treatment of carbapenem-resistant A. baumannii VAP is warranted.

Incidence and risk factors for endocarditis among patients with health care-associated Staphylococcus aureus bacteraemia.

BACKGROUND: Staphylococcus aureus infective endocarditis (IE) is a characteristic community-acquired infection, however most cases are presently occurring in the health care setting. This study investigated the incidence and risk factors for S. aureus IE in patients with nosocomial and health care-associated S. aureus bacteraemia (SAB). METHODS: Consecutive patients with health care-associated and hospital-acquired SAB were prospectively recruited over a 30-month period. Patients were followed up for at least 12 weeks after the initial positive blood culture result. The primary endpoint was the diagnosis of IE. RESULTS: IE occurred in 11 of 303 patients (3.6%). Patient characteristics at diagnosis and that were associated with IE included the number of positive blood cultures obtained during hospitalization (p = 0.003), the duration of bacteraemia (p < 0.001), bacteraemia persisting for > 3 days (odds ratio (OR) 14.5, 95% confidence interval (CI) 4.0-52.8; p < 0.001), performance of echocardiography (OR 1.88, 95% CI 1.69-2.1; p = 0.001), presence of a well known predisposing risk for IE (OR 57.2, 95% CI 13.6-240.5; p < 0.001), a non-fatal McCabe score (OR 2.10, 95% CI 1.4-3.1; p = 0.02), and the duration of fever related to the infection (p = 0.026). On multivariable analysis, the presence of a predisposing risk for IE, prolonged bacteraemia, and non-fatal McCabe score remained significantly associated with IE. CONCLUSIONS: In this study the incidence of IE was lower than previously reported. Three clinical characteristics were identified as risk factors for IE among patients with SAB acquired in a health care setting.

Outcome of Pneumocystis jirovecii pneumonia diagnosed by polymerase chain reaction in patients without human immunodeficiency virus infection.

BACKGROUND AND OBJECTIVE: Pneumonia caused by Pneumocystis jirovecii (PCP) in patients without human immunodeficiency virus (HIV) infection is associated with high mortality. The diagnosis of PCP at our institution is based on detection of DNA using a polymerase chain reaction (PCR) assay. The aim of this study was to describe the clinical manifestations, outcomes and factors associated with mortality due to PCP, as diagnosed by PCR, in patients without HIV infection. METHODS: Over a 6-year period, all HIV-negative immunocompromised patients suspected of having an opportunistic pulmonary infection underwent diagnostic bronchoscopy. A multigene PCR assay that detects Pneumocystis jirovecii DNA was used for the diagnosis of PCP. Patients were considered to have PCP if they had underlying immunodeficiency, compatible signs and symptoms, abnormal radiological findings, and Pneumocystis jirovecii DNA was detected in a bronchoalveolar lavage fluid sample. Data was collected retrospectively. RESULTS: PCP was diagnosed in 58 patients. The underlying conditions included haematological malignancies (60.3%), solid tumours (17.2%) and immunosuppressive treatment (22.4%). The most common clinical features in patients with PCP were fever (94.6%), dyspnoea (67.2%) and cough (36.2%). The overall in-hospital mortality was 17.2% (10/58). Mortality was associated with co-infections, high lactate dehydrogenase levels, female gender, and higher pneumonia severity index and acute physiology and chronic health evaluation III scores. CONCLUSIONS: In this study, the mortality of HIV-negative patients with PCP was low compared with previous reports. We hypothesize that this finding resulted from the increased sensitivity of a PCR-based assay, as compared with traditional methods, for the diagnosis of PCP in HIV-negative patients.

Soft tissue infections caused by marine bacterial pathogens: epidemiology, diagnosis, and management.

Skin and soft tissue infections (SSTIs) are one of the most common infection syndromes and may be caused by a large number of microorganisms. Some principles of aquatic injuries are different than those of land-based trauma. Wounds sustained in marine environment are exposed to a milieu of bacteria rarely encountered in different settings. These include Vibrio spp., Aeromonas spp., Shewanella spp., Erysipelothrix rhusiopathiae, Mycobacterium marinum, Streptococcus iniae, and other microbes. Failure to recognize and treat these uncommon pathogens in a timely manner may result in significant morbidity or death. These infections are frequently contracted as a result of recreational swimming, fishing injuries, or seafood handling. The spectrum of manifestations is wide, varying from cases of mild cellulitis, to severe life-threatening necrotizing fasciitis requiring radical surgery, to sepsis and death. This review will focus on the epidemiology, clinical manifestations, and treatment of SSTIs caused by the most important marine pathogens.

Attributable mortality of nosocomial Acinetobacter bacteremia.

OBJECTIVE: To determine the attributable mortality and outcome of nosocomial Acinetobacter bacteremia. DESIGN: Matched, retrospective cohort study. SETTING: Large, university-based, tertiary care center. PATIENTS: Of 219 patients with nosocomial Acinetobacter bacteremia identified by prospective surveillance during a 3-year period, 52 met the criteria for the study and were matched to a control patient by age, sex, primary and secondary diagnosis, operative procedures, and date of admission. RESULTS: A 100% success rate was achieved in the proportion of case patients and control patients matched for the compared criteria, except for major operative procedures (88%) and the presence of an important secondary underlying disease (54.5%). Twenty-nine (55.7%) of the case patients died, compared with 10 (19.2%) of the control patients (P<.001). The attributable mortality was 36.5% (95% CI, 27%-46%) and the risk ratio for death was 2.9 (95% CI, 1.58-5.32). In a multivariate survival analysis, older age, mechanical ventilation, renal failure, and Acinetobacter bacteremia (hazard ratio [HR], 4.41; 95% confidence interval [CI], 1.97-9.87; P<.001) were found to be independent predictors of mortality. There was a trend for a longer median duration of hospitalization among case patients, compared with control patients (11.5 vs. 6.5 days; P=.06). Three isolates were resistant to all but 1 antibiotic tested (colistin), and 45 isolates (86.5%) were resistant to 4 or more different antibiotic classes. CONCLUSIONS: When adjusted for risk-exposure time and severity of disease at admission, nosocomial Acinetobacter bacteremia is associated with mortality in excess of that caused by the underlying diseases alone.

Contamination of peripheral hematopoeitic stem cell products with a Mycobacterium mucogenicum-related pathogen.

A gram-positive rod with a restriction pattern closely related to the published nucleotide sequence of Mycobacterium mucogenicum was isolated from 6 of 45 units of peripheral blood stem cell products. The source of the contamination was traced to ice cubes used in processing the peripheral blood stem cell products. Substituting reusable ice trays for ice from an ice machine terminated the outbreak.

Clusters of Mediterranean spotted fever in Israel.

Mediterranean spotted fever (MSF) usually occurs as sporadic cases. We report five clusters of MSF in Israel. Each cluster consisted of two to three patients. In two clusters, one patient died while the other recovered. In the other three clusters the patients presented with a benign course of the disease. The diagnosis of MSF in the fatal cases was confirmed by nested-polymerase chain reaction (PCR) tests performed on samples obtained from internal organs. Rickettsial DNA was also found in a tick obtained from a dog owned by one of the patients. MSF was diagnosed in the recovered patients by serology. The diagnosis of MSF fever in one family member should raise the awareness to the possibility of other cases in the vicinity.

Surgical site infection rates following cardiac surgery: the impact of a 6-year infection control program.

BACKGROUND: To evaluate the impact of an infection control program on surgical site infections (SSIs) complicating cardiac operations. METHODS: Prospective cohort study of patients undergoing cardiac operations. Interventions included prospective surveillance, povidone-iodine scrub showers, depilation before surgery, administration of preoperative antibiotic prophylaxis in the operating room, and postdischarge follow-up. Logistic regression models were fitted to assess infection rates over time, adjusting for factors known to affect SSI rates. RESULTS: The overall SSI rate for 2051 procedures was 10.4%. Rates of superficial and deep incisional SSIs remained unchanged over the study period. The rates of all organ/space infections, mediastinitis, and SSIs because of methicillin-resistant Staphylococcus aureus during the first 2 years were 3.25%, 2.22%, and 1.48%, respectively, and they decreased to 1.17%, 0.73%, and 0.73%, respectively, by the end of 2002 (P = .01, P = .01, and P = .09, respectively). The adjusted odds ratios for these 3 types of infection at the end of 2002 compared with December 31, 1998, were 0.19 (95% confidence interval [95% CI]: 0.07-0.48), 0.20 (95% CI: 0.06-0.66), and 0.28 (95% CI: 0.08-0.97), respectively. CONCLUSION: We observed significant reductions in organ/space infection rates, particularly mediastinitis. These differences remained significant when adjusted for potential confounding variables.

Effect of preoperative antibiotic prophylaxis on surgical site infections complicating cardiac surgery.

OBJECTIVE: To evaluate the effect of an optimized policy for antibiotic prophylaxis on surgical site infection (SSI) rates in cardiac surgery. DESIGN: Prospective cohort study. SETTING: Tertiary medical center in Israel. METHODS: SSIs were recorded during a 10-year study period and ascertained through routine surveillance using the National Healthcare Safety Network (NHSN) methodology. Multivariable analyses were conducted to determine which significant covariates, including the administration of preoperative prophylaxis, affected these outcomes. RESULTS: A total of 2,637 of 3,170 evaluated patients were included, and the overall SSI rate was 8.4%. A greater than 50% reduction in SSI rates was observed in the last 4 years of the study. Overall and site-specific infection rates were similar for patients receiving cefazolin or vancomycin. SSIs developed in 206 (8.1%) of the 2,536 patients who received preoperative prophylaxis (within 2 hours of the first incision) compared with 14 (13.9%) of 101 patients who received antibiotic prophylaxis at a different time (P = .04; odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0-3.3). After accounting for covariates, preoperative hospital stay (5 days or more), an NHSN risk category (2 or 3), age (60 years or more), surgeon's role, and the period of measurement were significantly associated with SSIs. Emergency surgery, age, surgeon's role, and nonpreoperative prophylaxis were found to be independent predictors of superficial SSI. CONCLUSIONS: We observed a progressive and significant decrease in SSI rates after the implementation of an infection control program that included an optimized policy of preoperative prophylaxis in cardiac surgery.

Blood stream infections (BSI) in severe burn patients--early and late BSI: a 9-year study.

Bloodstream infections (BSI) and sepsis are among the most common complications occurring in severe burn patients. This study was designed to evaluate changes in BSI pathogens over almost a decade in severe burn patients at Rambam Healthcare Campus, and BSI occurrence during early and late hospitalization periods. Retrospective computerized data was retrieved from all severe burn patients hospitalized in our institution during the years 2001-2009. BSI in the first week was defined as early BSI, and in the second week and beyond, late BSI. Of 159 severe burns patients, 74 had at least one BSI episode. Most first BSI episodes were diagnosed during the first week of hospitalization. In late BSI, an increased prevalence of resistant bacteria (methicillin-resistant Staphylococcus aureus [MRSA], carbapenem-resistant Klebsiella pneumoniae [CRKP], imipenem-resistant Pseudomonas aeruginosa [PSE-IMP]) and Candida spp. were observed. However, over the 9-year study period, only CRKP increased significantly. In summary, except for the sudden appearance and increase in CRKP (8% increase; p=0.045), we did not observe a significant change in the BSI pathogen profile over the 9-year period. Nevertheless, over the hospitalization period, there is a clear change in the BSI bacteria profile, especially after 4 weeks of hospitalization.

A nationwide surveillance of invasive pneumococcal disease in adults in Israel before an expected effect of PCV7.

Pneumococcal infections in adults vary in severity and incidence is affected by childhood vaccination policy. Here, we try to define the host determinants and the interaction with specific serotypes that result in invasive pneumococcal disease (IPD) before an expected effect of pneumococcal conjugate vaccines. A nationwide active surveillance was initiated on July 2009, at the time of national implementation of PCV7 in Israel. The surveillance included all 27 laboratories and medical centers performing blood cultures in Israel, providing all blood and CSF pneumococcal isolates from persons ≥18y. Capture-recapture method assured that >95% of all cases were reported. IPD outcome and medical history were recorded and isolates were serotyped. Four hundred and sixty IPD cases were reported (annual incidence [/100,000] of 9.25). Incidence increased with age, from 2.6 among 18-34y to 66.8 among ≥85y. The most common diagnosis was pneumonia (72.4%), followed by bacteremia with no apparent focus (20.2%). Case fatality rate increased with age and number of comorbidities (34.5% for ≥75y or those with ≥3 comorbidities vs. 9.2-11.2% among <65y or those with no comorbidities; p=0.015). Variables independently associated with mortality were: age ≥75, chronic renal failure, malignancy, neurosurgery, alcohol abuse, multi-lobar pneumonia and sepsis with no apparent focus. The predominant serotypes in patients 18-49y were 1, 5, 8, 7F and 9V (constituting 56.3% in this age-group vs. 11.9% in ≥75y; p<0.01). The predominant serotypes among patients ≥75y were 3, 19A, 23F and 14 (40.3% of this age-group vs. 12.9% of 18-49y; p<0.01). Overall, PCV7 and PCV13 covered 25.6% and 63.7% of isolates, respectively, and 30.9% and 67.9% of isolates in mortality cases respectively. This nationwide active surveillance provides the baseline incidence, mortality rates and risk group distributions of IPD in adults before expected PCV effect.

Eradication of carbapenem-resistant Enterobacteriaceae gastrointestinal colonization with nonabsorbable oral antibiotic treatment: A prospective controlled trial.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are emerging. In attempt to eradicate CRE colonization, we conducted a semirandomized, prospective, controlled trial using oral nonabsorbable antibiotics. METHODS: Consecutive hospitalized CRE carriers were studied. Patients whose rectal isolates were gentamicin sensitive but colistin resistant were treated with gentamicin. Patients whose isolates were colistin sensitive but gentamicin resistant were treated with colistin. Patients whose isolates were sensitive to both drugs were randomized to 3 groups of oral antibiotic treatment: gentamicin, colistin, or both. Patients whose isolates were resistant to both drugs, and those who did not consent, were followed for spontaneous eradication. RESULTS: One hundred fifty-two patients were included; 102 were followed for spontaneous eradication for a median duration of 140 days (controls), and 50 received 1 of the 3 drug regimens: gentamicin, 26; colistin, 16; both drugs, 8, followed for a median duration of 33 days. Eradication rates in the 3 treatment groups were 42%, 50%, and 37.5%, respectively, each significantly higher than the 7% spontaneous eradication rate in the control group (P < .001, P < .001, and P = .004, respectively) with no difference between the regimens. No significant adverse effects were observed. CONCLUSION: Oral antibiotic treatment with nonabsorbable drugs to which CRE is susceptible appears to be an effective and safe for eradication of CRE colonization and, thereby, may reduce patient-to-patient transmission and incidence of clinical infection with this difficult-to-treat organism.

Polymerase chain reaction-based detection of Pneumocystis jirovecii in bronchoalveolar lavage fluid for the diagnosis of pneumocystis pneumonia.

INTRODUCTION: The diagnosis of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected immunocompromised patients is notoriously difficult. The recent advent of polymerase chain reaction (PCR)-based detection systems, based on the identification of single fungal genes, has markedly improved diagnostic accuracy in this ominous disease. In an attempt to further improve diagnostic yield, the authors used a PCR-based detection system for Pneumocystis jirovecii, based on targeting 3 distinct genes. METHODS: During the 4-year period (January 2005 to January 2009), all consecutive immunocompromised patients suspected of having PCP in the differential diagnosis underwent bronchoscopy with bronchoalveolar lavage sampling for the evaluation of the etiology of pulmonary infiltrates. Bronchoalveolar fluid was tested for the presence of a wide variety of possible etiological microorganisms. RESULTS: In a cohort of 214 immunocompromised patients (of which 198 were non-HIV immunocompromised patients) who underwent bronchoscopy with bronchoalveolar lavage for evaluation of pulmonary infiltrates, PCR correctly diagnosed PCP in 75% (42/56) compared with 14% (8/56) diagnosed by traditional stains, and increased diagnostic yield 5.4-fold. CONCLUSIONS: Given the absence of a sensitive gold standard, this study demonstrates the usefulness of a multigene PCR-based detection of Pneumocystis jirovecii DNA for supporting the clinical diagnosis of PCP, with high sensitivity and negative predictive value rates compared with direct stains, especially in non-HIV immunocompromised patients.

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).

Carbapenem resistance among Klebsiella pneumoniae isolates: risk factors, molecular characteristics, and susceptibility patterns.

BACKGROUND: Carbapenem resistance among isolates of Klebsiella pneumoniae has been unusual. OBJECTIVES: To identify risk factors for infection with carbapenem-resistant K. pneumoniae (CRKP) and to characterize microbiological aspects of isolates associated with these infections. DESIGN: Retrospective case-control study. SETTING: A 900-bed tertiary care hospital. RESULTS: From January 2006 through April 2007, K. pneumoniae was isolated from 461 inpatients; 88 had CRKP infection (case patients), whereas 373 had carbapenem-susceptible K. pneumoniae infection (control subjects). The independent risk factors for infection with CRKP were prior fluoroquinolone use (odds ratio [OR], 1.87 [95% confidence interval [CI], 1.07-3.26]; P=.026), previous receipt of a carbapenem drug (OR, 1.83 [95% CI, 1.02-3.27]; P=.042), admission to the intensive care unit (OR, 4.27 [95% CI, 2.49-7.31]; P<.001), and exposure to at least 1 antibiotic drug before isolation of K. pneumoniae (OR, 3.93 [95% CI, 1.15-13.47]; P=.029). All CRKP isolates carried the bla(KPC) gene. Approximately 90% of the tested isolates carried the bla(KPC-2) allele, suggesting patient-to-patient transmission. Almost all CRKP isolates were resistant to all antibiotics, except to colistin (resistance rate, 4.5%), gentamicin (resistance rate, 7%), and tigecycline (resistance rate, 15%). CONCLUSIONS: CRKP should be regarded as an emerging clinical threat. Because these isolates are resistant to virtually all commonly used antibiotics, control of their spread is crucial.

Listeria monocytogenes infection in Israel and review of cases worldwide.

Listeria monocytogenes, an uncommon foodborne pathogen, is increasingly recognized as a cause of life-threatening disease. A marked increase in reported cases of listeriosis during 1998 motivated a retrospective nationwide survey of the infection in Israel. From 1995 to 1999, 161 cases were identified; 70 (43%) were perinatal infections, with a fetal mortality rate of 45%. Most (74%) of the 91 nonperinatal infections involved immunocompromised patients with malignancies, chronic liver disease, chronic renal failure, or diabetes mellitus. The common clinical syndromes in these patients were primary bacteremia (47%) and meningitis (28%). The crude case-fatality rate in this group was 38%, with a higher death rate in immunocompromised patients.