Francisc Schlaeffer

Attributable Mortality Rate for Carbapenem-Resistant Klebsiella pneumoniae Bacteremia

OBJECTIVE To determine the attributable (direct) mortality and morbidity caused by carbapenem-resistant Klebsiella pneumoniae bacteremia. DESIGN A matched retrospective, historical cohort design, using a stepwise procedure to stringently match the best control subjects to the best case subjects. SETTING A 1,000-bed tertiary-care university teaching hospital. PATIENTS Case subjects were defined as adult patients with carbapenem-resistant K. pneumoniae bacteremia during the period from October 2005 through October 2008. Control subjects were defined as patients who were very similar to case subjects except that they did not have bacteremia. METHODS Matching potential control subjects to case subjects was performed at a 1:1 ratio using a computerized record system. The criteria used included same hospitalization period, similar Charlson comorbidity index, same underlying disease, same age within 10 years, and same sex. Demographic and clinical characteristics were collected from medical records. RESULTS During the study period, 319 patients developed an infection due to carbapenem-resistant K. pneumoniae. Of these 319 patients, 39 (12.2%) developed a bloodstream infection, for an overall rate of 0.59 episodes of carbapenem-resistant K. pneumoniae bacteremia per 10,000 patient-days. We excluded 7 patients from our study, leaving a total of 32 case subjects in our cohort. Case subjects were significantly more likely than control subjects (n = 32) to require care in an intensive care unit (12 case subjects [37.5%] vs 3 control subjects [9.4%]), ventilator support (17 case subjects [53.1%] vs 8 control subjects [25%]), and use of a central venous catheter (19 case subjects [59.4%] vs 9 control subjects [28.1%]). For case subjects, the crude mortality rate was 71.9% (ie, 23 of the 32 case subjects died); for control subjects, the crude mortality rate was 21.9% (ie, 7 of the 32 control subjects died) (P < .001. For case subjects, the attributable mortality was 50% (95% confidence interval [CI], 15.3%-98.6%). A mortality risk ratio of 3.3 (95% CI, 2.9-28.5) was found for case subjects with carbapenem-resistant K. pneumoniae bacteremia. CONCLUSIONS Patients with carbapenem-resistant K. pneumoniae require more intensive and invasive care. We have shown that the crude and attributable mortality rates associated with carbapenem-resistant K. pneumoniae bacteremia were striking.

Pharmacokinetic dosing of aminoglycosides: a controlled trial

PURPOSE To evaluate whether individualized pharmacokinetic dosing of aminoglycosides can reduce nephrotoxicity and improve the outcome of patients with gram-negative sepsis. METHODS We conducted a prospective controlled trial at a tertiary care university hospital. Eighty-one patients with suspected or documented gram-negative infections were enrolled. All were treated with either gentamicin or amikacin, according to clinical judgement. Patients were allocated to one of two groups based on the last digit (odd/even) of their identification number. In the study group (pharmacokinetic dosing) of 43 patients, plasma aminoglycoside levels were determined 1 hour after initiation of drug infusion and 8 to 16 hours later to estimate the elimination half-life and volume of distribution, from which the subsequent dosage schedule was calculated. Target peak plasma levels were 20 microg/mL for gentamicin and 60 microg/mL for amikacin. Target trough levels were <1 microg/mL for both drugs. The control group (fixed once-daily dosing) consisted of 38 patients who were prescribed single daily doses of gentamicin or amikacin. The primary endpoints were renal toxicity (> or = 25% increase in serum creatinine level or a serum creatinine level > or = 1.4 mg/dL) and 28-day mortality. RESULTS The two study groups were similar in age, sex, indications for therapy, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and clinical assessment at baseline. Although the pharmacokinetic group received significantly greater doses of aminoglycosides than did the once-daily group, the incidence of nephrotoxicity was significantly lower in the pharmacokinetic group (5% [2/43] vs. 21% [8/38], P = 0.03). There was no statistically significant difference in 28-day mortality (27% [12/43] vs. 22% [8/38], P = 0.3). CONCLUSION These results suggest that individualized pharmacokinetic dosing of aminoglycosides reduces the incidence of nephrotoxicity and allows the use of greater doses of aminoglycosides.

A Randomized, Double-Blind, Placebo-Controlled Trial of Selective Digestive Decontamination Using Oral Gentamicin and Oral Polymyxin E for Eradication of Carbapenem-Resistant Klebsiella pneumoniae Carriage

OBJECTIVE To assess the effectiveness of selective digestive decontamination (SDD) for eradicating carbapenem-resistant Klebsiella pneumoniae (CRKP) oropharyngeal and gastrointestinal carriage. DESIGN A randomized, double-blind, placebo-controlled trial with 7 weeks of follow-up per patient. SETTING A 1,000-bed tertiary-care university hospital. PATIENTS Adults with CRKP-positive rectal swab cultures. METHODS Patients were blindly randomized (1 :1) over a 20-month period. The SDD arm received oral gentamicin and polymyxin E gel (0.5 g 4 times per day) and oral solutions of gentamicin (80 mg 4 times per day) and polymyxin E (1 x 10(6) units 4 times per day for 7 days). The placebo arm received oral placebo gel 4 times per day and 2 placebo oral solutions 4 times per day for 7 days. Strict contact precautions were applied. Samples obtained from the throat, groin, and urine were also cultured. RESULTS Forty patients (mean age ± standard deviation, 71 ± 16 years; 65% male) were included. At screening, greater than or equal to 30% of oropharyngeal, greater than or equal to 60% of skin, and greater than or equal to 35% of urine cultures yielded CRKP isolates. All throat cultures became negative in the SDD arm after 3 days (P < .0001). The percentages of rectal cultures that were positive for CRKP were significantly reduced at 2 weeks. At that time, 16.1% of rectal cultures in the placebo arm and 61.1% in the SDD arm were negative (odds ratio, 0.13; 95% confidence interval, 0.02-0.74; P < .0016). A difference between the percentages in the 2 arms was still maintained at 6 weeks (33.3% vs 58.5%). Groin colonization prevalence did not change in either arm, and the prevalence of urine colonization increased in the placebo arm. CONCLUSIONS This SDD regimen could be a suitable decolonization therapy for selected patients colonized with CRKP, such as transplant recipients or immunocompromised patients pending chemotherapy and patients who require major intestinal or oropharyngeal surgery. Moreover, in outbreaks caused by CRKP infections that are uncontrolled by routine infection control measures, SDD could provide additional infection containment.

Risk factors for developing clinical infection with carbapenem-resistant Klebsiella pneumoniae in hospital patients initially only colonized with carbapenem-resistant K pneumoniae.

BACKGROUND This study examined predictors of carbapenem-resistant Klebsiella pneumoniae (CRKP) colonization and risk factors for the development of CRKP infection in patients initially only colonized with CRKP. METHODS A total of 464 patients with CRKP rectal colonization (CRKP-RC) were identified. Two case-control studies were performed, one comparing risk factors for CRKP-RC in patients who did not develop CRKP infection (CRKP-IN) versus patients without CRKP-RC and CRKP-IN, and the other comparing CRKP-RC patients who did not develop CRKP-IN with those who did. RESULTS Forty-two of the 464 colonized patients developed CRKP-IN. Multivariate analysis identified the following predictors for CRKP-RC: antibiotic therapy (odds ratio [OR], 5.76; P ≤ .0001), aminopenicillin therapy (OR, 7.753; P = .004), bedridden (OR, 3.09; P = .021), and nursing home residency (OR, 3.09; P = .013). Risk factors for CRKP-IN in initially CRKP-RC-positive patients were previous invasive procedure (OR, 5.737; P = .021), diabetes mellitus (OR, 4.362; P = .017), solid tumor (OR, 3.422; P = .025), tracheostomy (OR, 4.978; P = .042), urinary catheter insertion (OR, 4.696; P = .037), and antipseudomonal penicillin (OR, 23.09; P ≤ .0001). CONCLUSIONS We suggest that in patients with CRKP-RC, a strategy for preventing CRKP-IN might include limiting antipseudomonal penicillin and carbapenem use and preventing infections by closely following compliance with infection control bundles.

Syphilis and HIV co-infection.

Syphilis is a complex disease, which is sexually transmitted. The incidence of syphilis is rising all over the world, partly due to the increased transmission in HIV patients and other high risk groups such as men who have sex with men. Interestingly syphilis itself facilitates HIV infection in several ways. Great importance exists in recognition of both diseases and their complex interactions. This article will review the manifestations of syphilis in the context of HIV infected patients, and the challenging diagnosis and management of these patients.

Clinical significance and impact on mortality of extended-spectrum beta lactamase-producing Enterobacteriaceae isolates in nosocomial bacteremia.

During an 8-month period, 55 episodes of nosocomial bacteremia caused by Enterobacteriaceae species were identified in a tertiary medical center, of which 26 (47%) were caused by extended-spectrum beta lactamase (ESBL)-producing organisms. ESBL production was associated with resistance to aminoglycosides, fluoroquinolones, tetracycline and co-trimoxazole compared with non-ESBL-producing organisms (p < 0.01). By multivariate analysis, infection with ESBL-producing organisms was associated with previous antibiotic therapy and central venous catheter insertion and mortality was associated with heart failure, malignancy and a prolonged hospital stay. Nineteen (73%) patients infected with ESBL-producing organisms received adequate empirical antibiotic therapy and all 26 received adequate definitive therapy. The in-hospital mortality rate did not differ between patients infected with ESBL producers and those infected by non-ESBL-producing Enterobacteriaceae species [13/26 (50%) and 11/29 (38%), respectively] (p > 0.5).During an 8-month period, 55 episodes of nosocomial bacteremia caused by Enterobacteriaceae species were identified in a tertiary medical center, of which 26 (47%) were caused by extended-spectrum beta lactamase (ESBL)-producing organisms. ESBL production was associated with resistance to aminoglycosides, fluoroquinolones, tetracycline and co-trimoxazole compared with non-ESBL-producing organisms (p < 0.01). By multivariate analysis, infection with ESBL-producing organisms was associated with previous antibiotic therapy and central venous catheter insertion and mortality was associated with heart failure, malignancy and a prolonged hospital stay. Nineteen (73%) patients infected with ESBL-producing organisms received adequate empirical antibiotic therapy and all 26 received adequate definitive therapy. The in-hospital mortality rate did not differ between patients infected with ESBL producers and those infected by non-ESBL-producing Enterobacteriaceae species [13/26 (50%) and 11/29 (38%), respectively] (p > 0.5).

Community-Acquired Methicillin-Resistant Staphylococcus aureus in Institutionalized Adults with Developmental Disabilities

Methicillin-resistant Staphylococcus aureus (MRSA) has recently been reported to emerge in the community setting. We describe the investigation and control of a community-acquired outbreak of MRSA skin infections in a closed community of institutionalized adults with developmental disabilities. In a 9-month period in 1997, 20 (71%) of 28 residents had 73 infectious episodes. Of the cultures, 60% and 32% obtained from residents and personnel, respectively, grew S. aureus; 96% and 27% were MRSA. All isolates were genetically related by pulsed-field gel electrophoresis and belonged to a phage type not previously described in the region. No known risk factors for MRSA acquisition were found. However, 58 antibiotic courses had been administered to 16 residents during the preceding 9 months. Infection control measures, antibiotic restriction, and appropriate therapy resulted in successful termination of this outbreak. Selective antibiotic pressure may result in the emergence, persistence, and dissemination of MRSA strains, causing prolonged disease.

Impact of active monitoring of infection control practices on deep sternal infection after open-heart surgery

BACKGROUND Deep-sternal infection is a devastating complication after open-heart surgery. However, the association between infection control practices and deep-sternal infection rates is unclear. METHODS To identify contributors to increased deep-sternal infection rates in our institution, consecutive open-heart surgery patients were prospectively studied during two periods (75 and 40 days), including 66 and 40 patients, respectively. Active monitoring including 149 infection control practices was performed in the operating room and intensive care unit. End-points were deep-sternal infection rates and their relation to infection control practices. RESULTS Mean age was 62+/-11 years and 68% were males. Coronary bypass was performed in 82%. Clinical and surgical features were comparable, except that patients in period 2 were more likely to have heart failure (15% vs 1.5%, p = 0.01) and had a longer mean duration of surgery (277 vs 217 minutes, p < 0.005). Only 57 practices (38%) were adequately performed. The main categories showing inadequate practices were disinfection, traffic, hand-washing, and surgical attire of nonscrubbed personnel, anesthesiologists, and pump technicians. Many categories showed a statistically significant improvement between periods. Deep-sternal infection rates in prestudy and poststudy periods were 10% and 2.8%, respectively (p = 0.007). CONCLUSIONS Active monitoring among personnel involved in open-heart surgery resulted in a significant and sustained decrease in deep-sternal infection rates, through modification of human behavior and improvement of performance standards, probably mediated by the Hawthorne effect. Periodic active monitoring may be a valuable tool to achieve and even sustain such a decrease with tremendous implications on morbidity, costs, and quality of care.

A Multifaceted Intervention Strategy for Eradication of a Hospital-Wide Outbreak Caused by Carbapenem-Resistant Klebsiella pneumoniae in Southern Israel

OBJECTIVE To devise a local strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). DESIGN Quasi-experimental, before-and-after, interrupted time-series study. SETTING A 1,000-bed tertiary-care university teaching hospital. METHODS Retrospectively, all relevant data were collected from the medical records of patients with CRKP infections from May 2006 through April 2007, the preintervention period. From May 1, 2007, through May 1, 2010, the postintervention period, the intervention was applied and prospectively followed. The 5 key elements of this strategy were an emergency department flagging system, the building of a cohort ward, the eradication of clusters, environmental and personnel hand cultures, and a carbapenem-restriction policy. The demographic and clinical parameters of patients colonized by and/or infected with CRKP were collected from medical records. RESULTS A total of 10,680 rectal cultures were performed for 8,376 patients; 433 (5.16%) and 370 (4.4%) were CRKP-colonized and CRKP-infected patients, respectively, and 789 (98%) of 803 patients were admitted to the CRKP cohort ward. The CRKP infection density was reduced from 5.26 to 0.18 per 10,000 patient-days (P ≤ .001), and no nosocomial CRKP infections were diagnosed. Twenty-three percent of environmental cultures were found to be positive. Meropenem use was reduced from 283 ± 70.92 to 118 ± 74.32 defined daily doses per 1,000 patient-days (P ≤ .001). CONCLUSION This intervention produced an enormous impact on patient location, surveillance cultures, and antibiotic policies and a massive investment in infection control resources.

Hospital-acquired brevundimonas vesicularis septicaemia following open-heart surgery : Case report and literature review

Brevundimonas vesicularis (B. vesicularis) is a pseudomonad rarely encountered in human infection. A case of nosocomial septicaemia with this organism following open-heart surgery is presented, with a review of the literature. The isolate demonstrated resistance to ciprofloxacin and aztreonam, which has not yet been reported. Treatment with piperacillin/tazobactam resulted in full recovery. A review of the literature reveals that B. vesicularis is a virulent organism involved in serious infections such as central nervous system infection or bacteraemia, some of which are nosocomial. Meanwhile, empiric therapy for B. vesicularis infection should include a broad-spectrum antimicrobial agent until susceptibility results are known.Brevundimonas vesicularis (B. vesicularis) is a pseudomonad rarely encountered in human infection. A case of nosocomial septicaemia with this organism following open-heart surgery is presented, with a review of the literature. The isolate demonstrated resistance to ciprofloxacin and aztreonam, which has not yet been reported. Treatment with piperacillin/tazobactam resulted in full recovery. A review of the literature reveals that B. vesicularis is a virulent organism involved in serious infections such as central nervous system infection or bacteraemia, some of which are nosocomial. Meanwhile, empiric therapy for B. vesicularis infection should include a broad-spectrum antimicrobial agent until susceptibility results are known.