Comparative effectiveness of Clostridium difficile treatments: a systematic review.

BACKGROUND: Clostridium difficile infection is increasing in incidence and severity. The optimal treatment is unknown. PURPOSE: To determine whether, among adults with C. difficile infection, treatment with certain antibiotics compared with others results in differences in initial cure, recurrence, and harms. DATA SOURCES: MEDLINE, AMED, ClinicalTrials.gov, and Cochrane databases (search dates: inception through August 2011, limited to English-language reports); bibliography review. STUDY SELECTION: Randomized, controlled trials of adults with C. difficile infection, independent of outcomes, who were treated with medications available in the United States. Observational studies reporting strain were included. DATA EXTRACTION: Study design, inclusion and exclusion criteria, quality and strength of evidence as assessed by 2 reviewers, study definitions, and duration of treatment and follow-up. Outcomes included initial cure, recurrence, and treatment harms. DATA SYNTHESIS: 11 trials that included 1463 participants were identified. Three trials compared metronidazole with vancomycin; 8 compared metronidazole or vancomycin with another agent, combined agents, or placebo. Strain was analyzed in 1 trial and 2 cohort studies. No study comparing 2 antimicrobial agents demonstrated a statistically significant difference for initial cure; all comparisons were of low to moderate strength of evidence. Moderate-strength evidence from 1 study demonstrated that recurrence was decreased with fidaxomicin versus vancomycin (15% vs. 25%; difference, -10 percentage points [95% CI, -17 to -3 percentage points]; P=0.005). Subgroup analysis of a single study comparing metronidazole with vancomycin for patients who have severe C. difficile infection showed no difference by intention-to-treat analysis; this was rated as insufficient-strength evidence. Harms, when reported, did not differ between treatments in any study. LIMITATIONS: Definitions of diarrhea, C. difficile infection, initial cure, and relapse varied. Some studies reported insufficient detail to allow assessment of all randomly assigned participants or of harms. CONCLUSION: No antimicrobial agent is clearly superior for the initial cure of C. difficile infection. Recurrence is less frequent with fidaxomicin than with vancomycin. PRIMARY FUNDING SOURCE: U.S. Department of Health and Human Services.

Infectious Disease Consultation for Staphylococcus aureus Bacteremia Improves Patient Management and Outcomes.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is a common, severe infectious disease with accepted standards of care. METHODS: A retrospective cohort study of all 233 SAB cases at the Minneapolis Veterans Affairs Medical Center (MVAMC) between October 2004 and February 2008 was performed to measure the impact of Infectious Disease (ID) consultation on conformance to standards and patient outcomes. Outcomes were classified as survived without relapse, relapsed, or died without relapse. ID involvement was classified as consultation, curbside, or no involvement. RESULTS: ID involvement occurred in 179/233 cases (77%). Management conformed to accepted standards in 162/197 cases (82%) evaluable for conformance. ID involvement was associated with increased conformance in univariable analysis and multivariable analysis adjusted for propensity for ID consultation (OR 5.9, 95% CI 2.5 - 13.8). Relapse occurred in 14/156 cases (9%) in which therapy conformed to standards compared with 8/35 cases (23%) in which therapy did not conform to standards (p=0.045). Relapse was more common in older patients (OR 1.05, CI 1.01-1.09) and in cases without ID involvement (OR 3.02, CI 1.003-9.1). Death was associated with greater Charlson Index scores (OR 1.89, CI 1.4-2.5). Of 111 cases with definitely or possibly infected devices, relapse occurred in 9/92 cases (9.8%) in which the device was wholly or partially removed compared with 6/19 cases (32%) in which the device was left in place (p=0.02). CONCLUSIONS: ID involvement in SAB cases was associated with increased adherence to accepted standards and fewer relapses. ID consultation should be performed for all SAB cases.

Physician preferences for elements of effective consultations.

BACKGROUND: Effective communication is vital for optimal medical consultation, but there is little current information about physician preferences for effective consultation. METHODS: We invited physicians with at least one post-graduate year of experience at four Minnesota teaching hospitals to complete a 16-question Internet questionnaire about inpatient consultations. RESULTS: E-mail requests were received by an estimated 651 physicians. Questionnaires were completed by 323 (50%). Of these, 54% had completed training >5 years before, 17% had completed training <5 years before, and 30% were residents or fellows. Three elements were considered essential in consultation requests by most respondents: the specific question to be addressed (94%), whom to call with the response (68%), and consultation urgency (66%). In the consultation note, 71% of subjects placed high importance on simple, concise recommendations and 64% on the rationale behind them, while only 7% placed high importance on citing references. Most (69%) preferred that assessments and recommendations be written in bulleted or numbered format. A plurality (48%) preferred that assessments and recommendations be separated. Most placed high value on recommendations regarding drug therapy that specify dose (80%), duration (80%), and generic medication name (62%). Requesters placed greater importance than consultants (87% vs. 65%, respectively, P = 0.004) on recommendations that included duration of therapy. The majority (63%) stated that telephone requests were needed for emergent or urgent consultations. Those who usually requested consultations were more likely than those who usually responded to consultation requests to prefer telephone requests for routine consultations (43% vs. 20%, P < 0.001). CONCLUSIONS: Physicians agreed on many essential elements for effective consultations. These results should guide efforts to improve communication in the consultation process and design electronic medical record systems.

Diagnosis and Management of Osteomyelitis Associated With Stage 4 Pressure Ulcers: Report of a Query to the Emerging Infections Network of the Infectious Diseases Society of America.

BACKGROUND: Few studies exist to guide the management of patients with stage 4 pressure ulcers with possible underlying osteomyelitis. We hypothesized that infectious disease (ID) physicians would vary widely in their approach to such patients. METHODS: The Emerging Infections Network distributed a 10-question electronic survey in 2018 to 1332 adult ID physicians in different practice settings to determine their approach to such patients. RESULTS: Of the 558 respondents (response rate: 42%), 17% had managed no such patient in the past year. Of the remaining 464 respondents, 60% usually felt confident in diagnosing osteomyelitis; the strongest clinical indicator of osteomyelitis reported was palpable or visible bone at the ulcer base. Approaches to diagnosing osteomyelitis in patients with visible and palpable bone varied: 41% of respondents would assume osteomyelitis, 27% would attempt pressure off-loading first, and 22% would perform diagnostic testing immediately. Preferred tests for osteomyelitis were bone biopsy (for culture and histopathology) and magnetic resonance imaging. Respondents differed widely on favored route(s) (intravenous, oral, or both) and duration of antimicrobial therapy but would treat longer in the absence, vs presence, of full surgical debridement (P < .001). Overall, 62% of respondents opined that osteomyelitis under stage 4 pressure ulcers is usually or almost always treated excessively, and most (59%) suggested multiple topics for future research. CONCLUSIONS: Regarding osteomyelitis underlying stage 4 pressure ulcers, ID physicians reported widely divergent diagnostic and treatment approaches. Most of the reported practice is not supported by the available evidence, which is quite limited and of low quality.

Elevated granulocyte colony-stimulating factor, non-infectious leukocytosis and fevers in a patient with multiple myeloma.

BACKGROUND: We report the case of a 56-year-old male with multiple myeloma in whom recurrent fevers and leukocytosis delayed potentially effective chemotherapy due to concern for active infection. DESIGN AND MEASUREMENTS: A thorough infectious workup, including CT and PET scans, was negative. The patient was eventually found to have an elevated serum granulocyte colony-stimulating factor (G-CSF) of 113 pg/ml (normal range 0.0 - 39.1 pg/ml), which was likely the cause of his persistent leukocytosis and fevers. Multiagent chemotherapy was initiated, and the fevers resolved in the next 4 days. RESULTS: Leukocyte concentrations trended down after initiation of chemotherapy, but it is uncertain how much of the decline was attributable to immunosuppression. CONCLUSION: We report this well-documented case to demonstrate that G-CSF production should be considered as a cause of unexplained fever and leukocytosis in patients with multiple myeloma to prevent inappropriate and delayed definitive diagnosis and treatment.

Comparison of Side Effects of the 2015-2016 High-Dose, Inactivated, Trivalent Influenza Vaccine and Standard Dose, Inactivated, Trivalent Influenza Vaccine in Adults ≥65 Years.

BACKGROUND: High-dose, inactivated, trivalent influenza vaccine (HD) is associated with higher rates of side effects than standard dose (SD) vaccine, which may represent a barrier to use. METHODS: We surveyed subjects ≥65 years who received either HD or SD vaccine at the Minneapolis Veteran Affairs Health Care System clinics on October 27, 28, or 29, 2015. Research assistants conducted a 17-item telephone survey of influenza vaccine recipients to inquire about self-reported health and symptoms experienced the week after vaccination. RESULTS: A total of 547 HD recipients and 541 SD recipients responded to the survey. The 2 groups were similar at baseline with respect to age, gender, and presence of high-risk medical conditions. At least ≥95% of individuals in both HD and SD groups reported that their overall health was the same or better than usual during the week after vaccination. Thirty-seven percent of HD recipients and 22% of SD recipients reported a local or systemic side effect (P < .001), most of which were mild to moderate. Only 7 of 547 (1.3%) HD recipients and 3 of 541 (0.6%) SD recipients reported a severe side effect (P = .34). There was no significant difference in healthcare visits between the groups. CONCLUSIONS: Side effects were more common among subjects ≥65 years who received HD influenza vaccine compared with SD vaccine. These side effects were well tolerated and were not associated with impairment of general health status. These findings should reassure patients and their providers of the safety and tolerability of the HD influenza vaccine.

Comparative Sensitivity of Transthoracic and Transesophageal Echocardiography in Diagnosis of Infective Endocarditis Among Veterans With Staphylococcus aureus Bacteremia.

BACKGROUND: Echocardiography is fundamental for diagnosing infective endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB), but whether all such patients require transesophageal echocardiography (TEE) is controversial. METHODS: We identified SAB cases between February 2008 and April 2012. We compared sensitivity and specificity of transthoracic echocardiography (TTE) and TEE for evidence of IE, and we determined impacts of IE risk factors and TTE image quality on comparative sensitivities of TTE and TEE and their impact on clinical decision making. RESULTS: Of 215 evaluable SAB cases, 193 (90%) had TTE and 130 (60%) had TEE. In 119 cases with both tests, IE was diagnosed in 29 (24%), for whom endocardial involvement was evident in 25 (86%) by TEE, vs only 6 (21%) by TTE (P < .001). Transesophageal echocardiography was more sensitive than TTE regardless of risk factors. Even among the 66 cases with adequate or better quality TTE images, sensitivity was only 4 of 17 (24%) for TTE, vs 16 of 17 (94%) for TEE (P < .001). Among 130 patients with TEE, the TEE results, alone or with TTE results, influenced treatment duration in 56 (43%) cases and led to valve surgery in at least 4 (6%). It is notable that, despite vigorous efforts to obtain both tests routinely, TEE was not done in 86 cases (40%) for various reasons, including pathophysiological contraindications (14%), patient refusal or other patient-related factors (16%), and provider declination or system issues (10%). CONCLUSIONS: Patients with SAB should undergo TEE when possible to detect evidence for IE, especially if the results might affect management.

Communication Between Infectious Disease Physicians and US State and Local Public Health Agencies: Strengths, Challenges, and Opportunities.

Strong working relationships between infectious disease (ID) physicians and public health have resulted in the early detection of emerging infectious threats. From May 6 through June 5, 2015, we surveyed ID physicians in the Infectious Diseases Society of America's Emerging Infections Network about communications with public health. A total of 688 of 1491 (46%) members completed the survey, 624 (91%) of whom knew how to reach their health department directly for an urgent issue. Only 38 (6%) described communications with their health department as poor. Interest in newer technologies (eg, mobile smartphone applications) showed mixed results. Interest in a smartphone application differed significantly by years of ID experience, with 81 of 146 (55%) respondents with <5 years of ID experience, 172 of 359 (48%) respondents with 5 to 24 years of ID experience, and 61 of 183 (33%) respondents with ≥25 years of ID experience in favor of a smartphone application (P < .001). As more physicians adopt newer communication technologies, health departments should be prepared to incorporate these tools to communicate with ID physicians.

Antimicrobial stewardship in outpatient settings: a systematic review.

OBJECTIVE: Evaluate the effect of outpatient antimicrobial stewardship programs on prescribing, patient, microbial outcomes, and costs. DESIGN: Systematic review METHODS: Search of MEDLINE (2000 through November 2013), Cochrane Library, and reference lists of relevant studies. We included English language studies with patient populations relevant to the United States (eg, infectious conditions, prescription services) evaluating stewardship programs in outpatient settings and reporting outcomes of interest. Data regarding study characteristics and outcomes were extracted and organized by intervention type. RESULTS: We identified 50 studies eligible for inclusion, with most (29 of 50; 58%) reporting on respiratory tract infections, followed by multiple/unspecified infections (17 of 50; 34%). We found medium-strength evidence that stewardship programs incorporating communication skills training and laboratory testing are associated with reductions in antimicrobial use, and low-strength evidence that other stewardship interventions are associated with improved prescribing. Patient-centered outcomes, which were infrequently reported, were not adversely affected. Medication costs were generally lower with stewardship interventions, but overall program costs were rarely reported. No studies reported microbial outcomes, and data regarding outpatient settings other than primary care clinics are limited. CONCLUSIONS: Low- to moderate-strength evidence suggests that antimicrobial stewardship programs in outpatient settings improve antimicrobial prescribing without adversely effecting patient outcomes. Effectiveness depends on program type. Most studies were not designed to measure patient or resistance outcomes. Data regarding sustainability and scalability of interventions are limited.

Diagnostic Errors that Lead to Inappropriate Antimicrobial Use.

OBJECTIVE: We found previously that inappropriate inpatient antimicrobial use was often attributable to erroneous diagnoses. Here, we detail diagnostic errors and their relationship to inappropriate antimicrobial courses. DESIGN: Retrospective cohort study. SETTING: Veterans Affairs hospital. PATIENTS: A cohort of 500 randomly selected inpatients with an antimicrobial course. METHODS: Blinded reviewers judged the accuracy of the initial provider diagnosis for the condition that led to an antimicrobial course and whether the course was appropriate. RESULTS The diagnoses were correct in 291 cases (58%), incorrect in 156 cases (31%), and of indeterminate accuracy in 22 cases (4%). In the remaining 31 cases (6%), the diagnosis was a sign or symptom rather than a syndrome or disease. The odds ratio of a correct diagnosis was 4.3 (95% confidence interval [CI], 2.2-8.5) if the index condition was related to the reason for admission. When the diagnosis was correct, 181 of 292 courses (62%) were appropriate, compared with only 10 of 208 (5%) when the diagnosis was incorrect or indeterminate or when providers were treating a sign or symptom rather than a syndrome or disease (P<.001). Among the 309 cases in which antimicrobial courses were not appropriate, reasons varied by diagnostic accuracy; in 81 of 111 cases (73%) with a correct diagnosis, incorrect antimicrobial(s) were selected; in 166 of 198 other cases (84%), antimicrobial therapy was not indicated. CONCLUSIONS: Diagnostic accuracy is important for optimal inpatient antimicrobial use. Antimicrobial stewardship strategies should help providers avoid diagnostic errors and know when antimicrobial therapy can be withheld safely.

Information resources used in antimicrobial prescribing.

To describe resources clinicians use when they prescribe antimicrobials, the authors surveyed prescribers by telephone within hours (median 2.9) after they ordered one or more antimicrobials for a patient. Among 157 prescribers, 87 (55%) used one or more external resources to aid in decisions about their order. The other 70 (45%) used only their own knowledge and experience. Fifty-nine (38%) consulted another person. Fifty-four (34%) used a print, computer, or Internet resource. In multivariate analysis, use of an external resource was associated with the clinician being on the medical service (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.41-6.3) or being an intern (OR 13.65, 95% CI 1.44-128). Eighty percent of providers said information about antimicrobial prescribing at the point of electronic order entry would be helpful. It was concluded that decision support at the point of electronic order entry is likely to be used and might improve antimicrobial prescribing.

A period of increased susceptibility to cigarette smoking among high school students.

Cross-sectional surveys of randomly selected high school students were conducted in October 1999 and in May 2000 to measure awareness of youth-led tobacco prevention efforts. A secondary goal of the surveys was to learn about tobacco use and attitudes. Respondents who never smoked cigarettes were asked if they had made a firm commitment to not smoke, and respondents who had not made such a commitment were considered susceptible. Among ninth graders, susceptibility increased from 31% in October to 47% in May, while susceptibility decreased from October to May for students in more advanced grades (p = 0.03, interaction of linear trends). Susceptibility was more common among students who felt smoking produced social benefits (OR 1.59, 95% CI 1.22-2.08) or who were tolerant of tobacco company behavior (OR 1.65, 95% CI 1.23-2.21), and less common among students who felt short-term adverse effects of cigarette smoking on health or hygiene were important to them (OR 0.74, 95% CI 0.56-0.97). Further studies should confirm the increase in susceptibility and its underlying mechanisms. Whether associated with ninth grade or with the first year in a new school, this previously unrecognized period of heightened susceptibility might represent an important opportunity for prevention.

Antimicrobial stewardship programs in inpatient hospital settings: a systematic review.

OBJECTIVE: Evaluate the evidence for effects of inpatient antimicrobial stewardship programs (ASPs) on patient, prescribing, and microbial outcomes. DESIGN: Systematic review. METHODS: Search of MEDLINE (2000 through November 2013), Cochrane Library, and reference lists of relevant studies. We included English language studies with patient populations relevant to the United States (ie, infectious conditions and prescriptions required for antimicrobials) that evaluated ASP interventions and reported outcomes of interest. Study characteristics and outcomes data were extracted and reviewed by investigators and trained research personnel. RESULTS: Few intervention types (eg, audit and feedback, guideline implementation, and decision support) substantially impacted patient outcomes, including mortality, length of stay, readmission, or incidence of Clostridium difficile infection. However, most interventions were not powered adequately to demonstrate impacts on patient outcomes. Most interventions were associated with improved prescribing patterns as measured by decreased antimicrobial use or increased appropriate use. Where reported, ASPs were generally associated with improvements in microbial outcomes, including institutional resistance patterns or resistance in the study population. Few data were provided on harms, sustainability, or key intervention components. Studies were typically of short duration, low in methodological quality, and varied in study design, populations enrolled, hospital setting, ASP intent, intervention composition and implementation, comparison group, and outcomes assessed. CONCLUSIONS: Numerous studies suggest that ASPs can improve prescribing and microbial outcomes. Strength of evidence was low, and most studies were not designed adequately to detect improvements in mortality or other patient outcomes, but obvious adverse effects on patient outcomes were not reported.

Use of a computer decision support system and antimicrobial therapy appropriateness.

OBJECTIVE: To determine whether antimicrobial (AM) courses ordered with an antimicrobial computer decision support system (CDSS) were more likely to be appropriate than courses ordered without the CDSS. DESIGN: Retrospective cohort study. Blinded expert reviewers judged whether AM courses were appropriate, considering drug selection, route, dose, and duration. SETTING: A 279-bed university-affiliated Department of Veterans Affairs (VA) hospital. PATIENTS: A 500-patient random sample of inpatients who received a therapeutic AM course between October 2007 and September 2008. Intervention. An optional CDSS, available at the point of order entry in the VA computerized patient record system. RESULTS: CDSS courses were significantly more likely to be appropriate (111/254, 44%) compared with non-CDSS courses (81/246, 33%, P = .013). Courses were more likely to be appropriate when the initial provider diagnosis of the condition being treated was correct (168/273, 62%) than when it was incorrect, uncertain, or a sign or symptom rather than a disease (24/227, 11%, P < .001. In multivariable analysis, CDSS-ordered courses were more likely to be appropriate than non-CDSS-ordered courses (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.13-2.98). Courses were also more likely to be judged appropriate when the initial provider diagnosis of the condition being treated was correct than when it was incorrect, uncertain, or a sign or symptom rather than a disease (OR, 3.56; 95% CI, 1.4-9.0). CONCLUSIONS: Use of the CDSS was associated with more appropriate AM use. To achieve greater improvements, strategies are needed to improve provider diagnoses of syndromes that are infectious or possibly infectious.

Cost of screening intensive care unit patients for methicillin-resistant Staphylococcus aureus in hospitals.

BACKGROUND: The objective of this study is to determine the costs per hospital admission of screening intensive care unit patients for methicillin-resistant Staphylococcus aureus (MRSA) and isolating those who are colonized. METHODS: Data on the costs of the intervention come from the Minneapolis Veterans Affairs Medical Center, a 279-bed teaching hospital and outpatient facility. A microcosting approach is used to determine the intervention costs for 3 different laboratory testing protocols. The costs of caring for MRSA-infected patients come from the experience of 241 Minneapolis Veterans Affairs Medical Center patients with MRSA infections in 2004 through 2006. The effectiveness of the intervention comes from the extant literature. To capture the effect of screening on reducing transmission of MRSA to other patients and its effect on costs, a Markov simulation model was employed. RESULTS: The intervention was cost saving compared with no intervention for all 3 laboratory processes evaluated and for all of the 1-way sensitivity analyses considered. CONCLUSION: Because of the high cost of caring for a MRSA patient, interventions that reduce the spread of infections-such as screening intensive care unit patients upon admission studied here-are likely to pay for themselves.

Excess costs and utilization associated with methicillin resistance for patients with Staphylococcus aureus infection.

OBJECTIVE: To determine differences in healthcare costs between cases of methicillin-susceptible Staphylococcus aureus (MSSA) infection and methicillin-resistant S. aureus (MRSA) infection in adults. DESIGN: Retrospective study of all cases of S. aureus infection. SETTING: Department of Veterans Affairs hospital and associated clinics. PATIENTS: There were 390 patients with MSSA infections and 335 patients with MRSA infections. METHODS: We used medical records, accounting systems, and interviews to identify services rendered and costs for Minneapolis Veterans Affairs Medical Center patients with S. aureus infection with onset during the period from January 1, 2004, through June 30, 2006. We used regression analysis to adjust for patient characteristics. RESULTS: Median 6-month unadjusted costs for patients infected with MRSA were $34,657, compared with $15,923 for patients infected with MSSA. Patients with MRSA infection had more comorbidities than patients with MSSA infection (mean Charlson index 4.3 vs 3.2; P < .001). For patients with Charlson indices of 3 or less, mean adjusted 6-month costs derived from multivariate analysis were $51,252 (95% CI, $46,041-$56,464) for MRSA infection and $30,158 (95% CI, $27,092-$33,225) for MSSA infection. For patients with Charlson indices of 4 or more, mean adjusted costs were $84,436 (95% CI, $79,843-$89,029) for MRSA infection and $59,245 (95% CI, $56,016-$62,473) for MSSA infection. Patients with MRSA infection were also more likely to die than were patients with MSSA infection (23.6% vs 11.5%; P < .001). MRSA infection was more likely to involve the lungs, bloodstream, and urinary tract, while MSSA infection was more likely to involve bones or joints; eyes, ears, nose, or throat; surgical sites; and skin or soft tissue (P < .001). CONCLUSIONS: Resistance to methicillin in S. aureus was independently associated with increased costs. Effective antimicrobial stewardship and infection prevention programs are needed to prevent these costly infections.

Nocardiosis in persons with human immunodeficiency virus infection, transplant recipients, and large, geographically defined populations.

To quantify the risk of nocardiosis in various populations, I systematically reviewed articles published between 1966 and 2004. The incidence of nocardiosis in 3 large, geographically defined populations ranged from 0.35 to 0.4 cases per 10(5) persons year. In contrast, the incidence of nocardiosis among people with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) in 1 study was 53 nocardiosis cases per 10(5) persons x year, approximately 140 times greater than that in the geographically defined populations. The frequency of nocardiosis cases in 4 populations of HIV-infected people averaged 608 cases per 10(5) persons. The incidence of nocardiosis in bone marrow-transplant recipients at 1 hospital was 128 cases per 10(5) persons x year, an incidence approximately 340 times greater than that in the geographically defined populations and in the same range as in HIV-infected people. The frequency of nocardiosis in 21 series of cases in recipients of a variety of transplanted organs averaged 1122 cases per 10(5) persons. These estimated incidence rates are imprecise because they were not collected through prospective surveillance systems, but the estimates for the 3 groups were internally consistent and provide useful information for clinicians.