Grace C. Lee

Treatment of Klebsiella Pneumoniae Carbapenemase (KPC) infections: a review of published case series and case reports

The emergence of Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria has become a significant global public health challenge while the optimal treatment remains undefined. We performed a systematic review of published studies and reports of treatment outcomes of KPC infections using MEDLINE (2001–2011). Articles or cases were excluded if one of the following was fulfilled: no individual patient data provided, no treatment regimen specified, no treatment outcome specified, report of colonization, or greater than three antibiotics were used to treat the KPC infection. Data extracted included patient demographics, site of infection, organism, KPC subtype, antimicrobial therapy directed at KPC-infection, and treatment outcome. Statistical analysis was performed in an exploratory manner. A total of 38 articles comprising 105 cases were included in the analysis. The majority of infections were due to K. pneumoniae (89%). The most common site of infection was blood (52%), followed by respiratory (30%), and urine (10%). Forty-nine (47%) cases received monotherapy and 56 (53%) cases received combination therapy directed at the KPC-infection. Significantly more treatment failures were seen in cases that received monotherapy compared to cases who received combination therapy (49% vs 25%; p= 0.01). Respiratory infections were associated with higher rates of treatment failure with monotherapy compared to combination therapy (67% vs 29% p= 0.03). Polymyxin monotherapy was associated with higher treatment failure rates compared to polymyxin-based combination therapy (73% vs 29%; p= 0.02); similarly, higher treatment failure rates were seen with carbapenem monotherapy compared to carbapenem-based combination therapy (60% vs 26%; p= 0.03). Overall treatment failure rates were not significantly different in the three most common antibiotic-class combinations: polymyxin plus carbapenem, polymyxin plus tigecycline, polymyxin plus aminoglycoside (30%, 29%, and 25% respectively; p=0.6). In conclusion, combination therapy is recommended for the treatment of KPC infections; however, which combination of antimicrobial agents needs to be established in future prospective clinical trials.

Risk of Major Bleeding with Concomitant Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients Receiving Long-Term Warfarin Therapy

Study Objectives. To characterize the safety of concomitant aspirin, clopidogrel, and warfarin therapy after percutaneous coronary intervention (PCI), and to identify patient characteristics that increase the risk of hemorrhage.

The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010

BACKGROUND Clostridium difficile infection (CDI) incidence is a growing concern. This study provides national estimates of CDI over 10 years and identifies trends in mortality and hospital length of stay (LOS) among hospitalized adults with CDI. METHODS We conducted a retrospective analysis of the US National Hospital Discharge Surveys from 2001-2010. Eligible cases included adults aged ≥ 18 years discharged from a hospital with an ICD-9-CM diagnosis code for CDI (008.45). Data weights were used to derive national estimates. CDI incidence rates were depicted as CDI discharges per 1,000 total adult discharges. RESULTS These data represent 2.2 million adult hospital discharges for CDI over the study period. CDI incidence increased from 4.5 CDI discharges per 1,000 total adult discharges in 2001 to 8.2 CDI discharges per 1,000 total adult discharges in 2010. The overall in-hospital mortality rate was 7.1% for the study period. Mortality increased slightly over the study period, from 6.6% in 2001 to 7.2% in 2010. Median hospital LOS was 8 days (interquartile range, 4-14 days), and remained stable over the study period. CONCLUSIONS The incidence of CDI among hospitalized adults in the United States nearly doubled from 2001-2010. Furthermore, there is little evidence of improvement in patient mortality or hospital LOS.

Treatment failure and costs in patients with methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections: A south Texas ambulatory research network (STARNet) study

Objective: To measure the incidence of treatment failure and associated costs in patients with methicillin-resistant Staphylococcus aureus skin and soft tissue infections (SSTIs). Methods: This was a prospective, observational study in 13 primary care clinics. Primary care providers collected clinical data, wound swabs, and 90-day follow-up information. Patients were considered to have “moderate or complicated” SSTIs if they had a lesion ≥5 cm in diameter or diabetes mellitus. Treatment failure was evaluated within 90 days of the initial visit. Cost estimates were obtained from federal sources. Results: Overall, treatment failure occurred in 21% of patients (21 of 98) at a mean additional cost of

Polymyxins and Doripenem Combination Against KPC-Producing Klebsiella pneumoniae

1,933.71 per patient. In a subgroup analysis of patients who received incision and drainage, those with moderate or complicated SSTIs had higher rates of treatment failure than those with mild or uncomplicated SSTIs (36% vs. 10%; P=.04). Conclusions: One in 5 patients presenting to a primary care clinic for a methicillin-resistant S. aureus SSTI will likely require additional interventions at an associated cost of almost

Clinical Epidemiology of Carbapenem-Resistant Enterobacteriaceae in Community Hospitals: A Case-Case-Control Study

2,000 per patient. Baseline risk stratification and new treatment approaches are needed to reduce treatment failures and costs in the primary care setting.

Trends in catheter-associated urinary tract infections among a national cohort of hospitalized adults, 2001-2010

Background Most KPC-producing organisms have maintained susceptibility to polymyxins; however, development of resistance to polymyxins has been increasingly reported. One potential treatment modality is to optimize the use of combination therapy. Therefore, we evaluated the in vitro activity of doripenem, colistin sulfate, polymyxin B alone and in combination against KPC- producing K. pneumoniae. Methods In-vitro time-kill assays were performed for four non-duplicate KPC-3 producing K. pneumoniae isolates with the following antibiotics: doripenem, polymyxin B and colistin sulfate alone and in combination. Bacterial densities were determined at 0, 4, 8, 12, 24 and 48 hours. Bactericidal activity was defined as ≥ 3-log10 CFU/mL reduction from the starting inoculum. Synergism was defined as ≥ 2-log10 reduction with the combination when compared to the most active single agent at 24 hours. Results Minimum inhibitory concentrations (MICs) for polymyxin B and colistin sulfate ranged from 0.0625 to 0.25 µg/mL, and all isolates were resistant to doripenem (MICs ranged 16 - 32 µg/mL). Monotherapy with colistin sulfate and polymyxin B displayed bacterialcidal activity within 12 hours; however, significant re-growth occurred by 24 hours in all isolates. Monotherapy with doripenem did not show bactericidal activity in any isolate. Synergy occurred with combinations of both colistin sulfate and polymyxin B with doripenem against all isolates and was sustained at 48 hours. Combinations of colistin sulfate or polymyxin B with doripenem demonstrated rapid bactericidal activity by 4 hours in all isolates and was sustained for 24 hours. Conclusion Polymyxin B and colistin sulfate in combination with doripenem may be an important treatment modality in treating KPC-producing organisms.

Regional and seasonal variation in Clostridium difficile infections among hospitalized patients in the United States, 2001-2010

Background: The occurrence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing at an alarming rate worldwide. Despite that increase, there are limited data identifying risk factors. Objective: To evaluate risk factors associated with the acquisition of CRE among hospitalized patients. Methods: We performed a retrospective case-case-control study in 4 community hospitals from June 2007 through June 2012. Case group 1 (CG1) consisted of patients with CRE. Case group 2 (CG2) consisted of patients with carbapenem susceptible Enterobacteriaceae (CSE). CG2 patients were matched to CG1 patients by site of infection and species of Enterobacteriaceae. Hospitalized controls were matched 2:1 by date of admission and hospital location to patients in CG1. Two sets of analyses were conducted comparing demographics, comorbidities, and antibiotic exposures of CG1 and CG2 to controls and then contrasted to identify unique risk factors associated with CRE. Results: Overall, 104 patients (CG1, 25 patients; CG2, 29 patients, control, 50 patients) were evaluated. CRE and CSE consisted mostly of Klebsiella spp. (63%) from a urinary source (28%). In multivariable analyses, intensive care unit (ICU) stay (OR 12.48; 95% CI 1.14-136.62; p = 0.04) and cumulative number of antibiotic days (OR 1.47; 95% CI 1.02-2.16; p = 0.04) were distinct independent predictors of CRE isolation; whereas, cumulative health care exposures (OR 2.03; 95% CI 1.20-3.41; p < 0.01) and vancomycin exposure (OR 6.70; 95% CI 1.15- 38.91; p = 0.03) were predictors for CSE. Conclusions: CRE should be considered in patients requiring ICU admission, particularly those who have received multiple antibiotics. Antibiotic stewardship efforts should be directed at reducing all antibiotic exposures as opposed to any specific antibiotic class to reduce the risk of CRE.

Comparative Whole Genome Sequencing of Community-Associated Methicillin-Resistant Staphylococcus aureus Sequence Type 8 from Primary Care Clinics in a Texas Community

BACKGROUND Catheter-associated urinary tract infections (CAUTIs) have become a major public health concern in the United States. This study provides national estimates of CAUTI incidence, mortality, and associated hospital length of stay (LOS) over a 10-year period. METHODS This was a retrospective analysis of the National Hospital Discharge Surveys from 2001 to 2010. Adults age ≥18 years with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure code for urinary catheter placement or other major procedure were included. Urinary tract infections were identified by ICD-9-CM code. Data weights were applied to derive national estimates. Predictors of CAUTI were identified using a logistic regression model. RESULTS These data represent 70.4 million catheterized patients, 3.8 million of whom developed a CAUTI. The incidence of CAUTIs decreased from 9.4 cases/100 catheterizations in 2001 to 5.3 cases/100 catheterizations in 2010. Mortality in patients with a CAUTI declined from 5.4% in 2001 to 3.7% in 2010. Median (interquartile range [IQR]) hospital LOS also declined, from 9 days (IQR, 5-16 days) in 2001 to 7 days (IQR, 4-12 days) in 2010. Independent predictors of CAUTI included female sex, emergency hospital admission, transfer from another facility, and Medicaid payment (P < .0001 for all variables). CONCLUSIONS The incidence of CAUTIs in US hospitals declined over the study period. Furthermore, patients with these infections experienced lower hospital mortality and shorter hospital LOS.

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BACKGROUND This study identified national regional and seasonal variations in Clostridium difficile infection (CDI) incidence and mortality among hospitalized patients in the United States over a 10-year period. METHODS This was a retrospective cohort study of the U.S. National Hospital Discharge Survey from 2001-2010. Eligible cases had an ICD-9-CM discharge diagnosis code for CDI (008.45). Data weights were used to derive national estimates. CDI incidence and mortality were presented descriptively. Regions were as defined by the U.S. Census Bureau. Seasons included the following: winter (December-February), spring (March-May), summer (June-August), and fall (September-November). RESULTS These data represent 2.3 million CDI discharges. Overall, CDI incidence was highest in the Northeast (8.0 CDIs/1,000 discharges) and spring (6.2 CDIs/1,000 discharges). CDI incidence was lowest in the West (4.8 CDIs/1,000 discharges) and fall (5.6 CDIs/1,000 discharges). Peak CDI incidence among children occurred in the West (1.7 CDI/1,000 discharges) and winter (1.5 CDI/1,000 discharges). Mortality among all CDI patients was highest in the Midwest (7.3%) and during the winter (7.9%). CONCLUSION The region and season with the highest CDI incidence rates among patients hospitalized in U.S. hospitals were the Northeast and spring, respectively. The highest CDI mortality rates were seen in the Midwest and winter. Children exhibited different regional and seasonal CDI variations compared with adults and older adults.