Incidence of Serotonin Syndrome With Combined Use of Linezolid and Serotonin Reuptake Inhibitors Compared With Linezolid Monotherapy.

PURPOSE: Linezolid is a monoamine oxidase inhibitor that may increase the risk of serotonin syndrome in patients receiving combination selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). The objective of this study was to compare the incidence of serotonin syndrome when linezolid was administered alone and in combination with SSRIs or SNRIs. METHODS: This was a retrospective case-control study of adult inpatients admitted to the University of Iowa Hospitals and Clinics who received linezolid between January 2010 and December 2014. Patients who received linezolid with or within 14 days of an SSRI or SNRI were eligible for inclusion in the combination therapy group. Patients who received linezolid alone were matched by age and gender to patients in the combination therapy group, and 3 monotherapy patients were included for each combination therapy patient. Clinical features consistent with serotonin syndrome were assessed using the Sternbach and Hunter criteria. RESULTS: A total of 348 patients were included in this study, of which 87 received combination therapy and 261 received linezolid monotherapy. One patient given combination therapy (1.1%) and 1 patient given linezolid monotherapy (0.4%) were determined to have a diagnosis of serotonin syndrome (P = 0.438; relative risk, 3.00; 95% confidence interval, 0.19-47.45). In both cases, signs and symptoms of serotonin syndrome reversed upon discontinuation of linezolid therapy. CONCLUSIONS: There was no significant difference in the incidence of serotonin syndrome when linezolid was used alone or in combination with an SSRI or SNRI, and the overall incidence of serotonin syndrome was low.

Knowledge and attitudes of doctor of pharmacy students regarding the appropriate use of antimicrobials.

Pharmacists are key partners in antimicrobial stewardship efforts, yet their degree of education on and attitudes toward this topic during training are not well documented. An electronic survey measuring knowledge and attitudes regarding antimicrobial use and resistance was administered to graduating pharmacy students at 12 US schools of pharmacy. Of 1445 pharmacy students, 579 (40%) completed the survey. The vast majority (94%) believed that strong knowledge of antimicrobials was important for their pharmacy careers, and 89% desired more education on appropriate antimicrobial use. Most students (84%) considered their pharmacy education regarding antimicrobials useful or very useful, but there was significant variability on perceptions of preparation for most antimicrobial stewardship activities according to the students' school. The mean number of correct answers on a section of 11 knowledge questions was 5.8 (standard deviation 2.0; P value for score between schools <.001). On multivariable linear regression analysis, significant predictors of a higher knowledge score were pharmacy school attended, planned postgraduate training, completion of a clinical rotation in infectious diseases, perception of pharmacy school education as useful, use of resources to answer the knowledge questions, and use of Infectious Diseases Society of America guidelines and smartphone applications as frequent resources for learning about antimicrobials. Pharmacy students perceive antimicrobial stewardship to be an important healthcare issue and desire more education on the subject. Student perceptions of antimicrobial coursework and actual antimicrobial knowledge scores significantly varied by the school of pharmacy attended. Sharing of best practices among institutions may enhance the preparation of future pharmacists to contribute to effective antimicrobial stewardship.

Urinary Tract Infection Frequency and Prescription Prophylaxis in Females and Males with Recurrent Urinary Tract Infection.

Females and males with recurrent urinary tract infections may receive prescription prophylaxis to reduce the infection frequency. Little is known about how prescription prophylaxis differs between patients meeting and exceeding the minimum threshold for recurrent urinary tract infections. The objectives of this study were to estimate the association between infection frequency and receipt of prescription prophylaxis and describe the type of prescription prophylaxis initiated. This observational study used de-identified fully-insured commercial insurance data from the Midwest from 2003-2016 to identify females and males under age 64 with recurrent urinary tract infections. The patients were categorized as having three or more urinary tract infections in twelve months or only two infections in six months. Multiple logistic regression models were used to determine the association between the infection frequency and receipt of prophylaxis. The frequency of the type of prophylaxis initiated was measured. The odds of receiving prophylaxis were greater in the females and males with three or more infections compared to the patients with only two infections. Estrogen prophylaxis was initiated at a higher rate in females aged 45-63 with two infections than the females with three or more infections. Prescription prophylaxis in females and males with recurrent urinary tract infections differs between those meeting and exceeding the minimum frequency threshold.

Systemic exposure to aminoglycosides following knee and hip arthroplasty with aminoglycoside-loaded bone cement implants.

BACKGROUND: Aminoglycoside-loaded bone cement (ALBC) implants are frequently used in orthopedic surgery. Parenteral aminoglycosides are known to cause nephrotoxicity. Reports of acute renal failure in patients receiving ALBC implants have been reported in the literature and at our hospital. OBJECTIVE: To evaluate, as part of a performance improvement project, whether patients undergoing arthroplasty procedures have detectable aminoglycoside serum concentrations following ALBC implantation and to evaluate corresponding changes in serum creatinine. METHODS: Patients undergoing hip or knee revision or resection who received an ALBC implant between January and April 2010 were included in our evaluation. In addition to baseline demographic information, we measured aminoglycoside concentrations and serum creatinine levels during the early postoperative period, prior to hospital discharge, and at the follow-up clinic visit when possible. RESULTS: Seventeen patients were evaluated: 13 women and 4 men with a mean age of 69 years (range 50-84). Eight patients had a preoperative diagnosis of infection and received high-dose ALBC implants as treatment and 9 patients received lower-dose ALBC implants for infection prophylaxis. Eight patients had detectable aminoglycoside serum concentrations (mean 0.42 µg/mL; range 0.3 to 2.0); 1 patient had an aminoglycoside serum concentration of 0.9 µg/mL on postoperative day 38. Patients who did not have a detectable aminoglycoside serum concentration on the first postoperative day did not have a detectable concentration in the following serum samples. Six patients had elevation of serum creatinine by greater than 0.3 mg/dL from baseline. CONCLUSIONS: The number of patients in this study is small; however, this report raises a potential concern for the safety of high-dose ALBC implants. We recommend measuring aminoglycoside serum concentrations in the early postoperative period to identify patients in need of further monitoring. Further studies are needed to determine risk factors for systemic toxicity.

Clinical Outcomes and Economic Impact of Oritavancin for Gram-Positive Infections: A Single Academic Medical Center Health System Experience.

BACKGROUND: Vancomycin treatment of complicated Gram-positive infections is associated with laboratory monitoring, nephrotoxicity, and multiple daily dosing. Oritavancin, a lipoglycopeptide antibiotic with a once-weekly dosing strategy and similar but slightly broader spectrum of activity, presents several opportunities over vancomycin to improve compliance and convenience for the patient. Minimal real-world clinical and acquisition cost data in the inpatient setting and clinical data surrounding multiple dosing in the outpatient setting have limited oritavancin use despite its potential logistic advantages. OBJECTIVES: We describe inpatient and outpatient oritavancin administration, clinical outcomes, and economic impact. METHODS: This was a single-center, retrospective case series of patients treated with at least one dose of oritavancin between May 2015 and September 2017 at an academic medical center in the USA. A simplified cost-avoidance analysis was conducted assuming the patient had a national health insurance plan and focused on hospital days prevented. RESULTS: Seventy-five patients received oritavancin during the study period. The most common use of oritavancin was in patients with acute bacterial skin and skin structure infections (ABSSSI), defined as cellulitis, abscess or non-surgical wounds (n = 25, 33%), followed by surgical wound infections (n = 12, 16%) and osteomyelitis or septic arthritis (n = 10, 13%). Clinical cure or improvement was achieved in 68 patients (93.2%), while five patients (6.8%) failed treatment; adverse reactions were reported in nine patients (12%). Thirty-five patients received oritavancin as inpatients; 20 patients (57%) had at least one hospital day avoided due to inpatient oritavancin administration resulting in a total cost avoidance of US$343,654. CONCLUSION: In this series of 75 patients with Gram-positive infections, oritavancin treatment resulted in clinical cure or improvement in most patients, and was generally well tolerated. Inpatient administration may avoid costs and outpatient administration is a reasonable consideration for patients in which prolonged antibiotic therapy is necessary.

Therapy and outcome of Candida glabrata versus Candida albicans bloodstream infection.

Candida glabrata is a common cause of bloodstream infection (BSI) and exhibits reduced susceptibility to antifungal agents. Those with C. glabrata BSI may therefore be at increased risk for a delay in receiving appropriate therapy and poor treatment outcome. We compared treatment and outcome of patients with C. glabrata to controls with Candida albicans BSI. Each patient with C. glabrata BSI from July 1997 through December 2004 was matched with a control patient infected with C. albicans. Appropriateness of therapy was defined using current guidelines, and the mortality end point was 30 days following the initial positive blood culture. Overall, 78% of patients received appropriate therapy (39/54 [72%] for C. glabrata versus 45/54 [83%] for C. albicans, P = 0.2). Crude 30-day mortality was high for both groups (41% for C. glabrata versus 44% for C. albicans, P = 0.7). There was no trend in mortality according to time of therapy initiation, but mortality was lower for those who received appropriate therapy (35% versus 71% for inappropriate therapy, P = 0.002). Twelve percent of patients received no antifungal therapy and contributed disproportionately to overall crude mortality. Strategies to decrease the incidence of untreated candidemia may favorably impact outcome.

Cost-effectiveness analysis of initial treatment strategies for mild-to-moderate Clostridium difficile infection in hospitalized patients.

PURPOSE: The cost-effectiveness of initial treatment strategies for mild-to-moderate Clostridium difficile infection (CDI) in hospitalized patients was evaluated. METHODS: Decision-analytic models were constructed to compare initial treatment with metronidazole, vancomycin, and fidaxomicin. The primary model included 1 recurrence, and the secondary model included up to 3 recurrences. Model variables were extracted from published literature with costs based on a healthcare system perspective. The primary outcome was the incremental cost-effective ratio (ICER) between initial treatment strategies. RESULTS: In the primary model, the overall percentage of patients cured was 94.23%, 95.19%, and 96.53% with metronidazole, vancomycin, and fidaxomicin, respectively. Expected costs per case were $1,553.01, $1,306.62, and $5,095.70, respectively. In both models, vancomycin was more effective and less costly than metronidazole, resulting in negative ICERs. The ICERs for fidaxomicin compared with those for metronidazole and vancomycin in the primary model were $1,540.23 and $2,828.69 per 1% gain in cure, respectively. Using these models, a hospital currently treating initial episodes of mild-to-moderate CDI with metronidazole could expect to save $246.39-$388.37 per case treated by using vancomycin for initial therapy. CONCLUSION: A decision-analytic model revealed vancomycin to be cost-effective, compared with metronidazole, for treatment of initial episodes of mild-to-moderate CDI in adult inpatients. From the hospital perspective, initial treatment with vancomycin resulted in a higher probability of cure and a lower probability of colectomy, recurrence, persistent recurrence, and cost per case treated, compared with metronidazole. Use of fidaxomicin was associated with an increased probability of cure compared with metronidazole and vancomycin, but at a substantially increased cost.

Implementation of a Mobile Clinical Decision Support Application to Augment Local Antimicrobial Stewardship.

BACKGROUND: Medical applications for mobile devices allow clinicians to leverage microbiological data and standardized guidelines to treat patients with infectious diseases. We report the implementation of a mobile clinical decision support (CDS) application to augment local antimicrobial stewardship. METHODS: We detail the implementation of our mobile CDS application over 20 months. Application utilization data were collected and evaluated using descriptive statistics to quantify the impact of our implementation. RESULTS: Project initiation focused on engaging key stakeholders, developing a business case, and selecting a mobile platform. The preimplementation phase included content development, creation of a pathway for content approval within the hospital committee structure, engaging clinical leaders, and formatting the first version of the guide. Implementation involved a media campaign, staff education, and integration within the electronic medical record and hospital mobile devices. The postimplementation phase required ongoing quality improvement, revision of outdated content, and repeated staff education. The evaluation phase included a guide utilization analysis, reporting to hospital leadership, and sustainability and innovation planning. The mobile application was downloaded 3056 times and accessed 9259 times during the study period. The companion web viewer was accessed 8214 times. CONCLUSIONS: Successful implementation of a customizable mobile CDS tool enabled our team to expand beyond microbiological data to clinical diagnosis, treatment, and antimicrobial stewardship, broadening our influence on antimicrobial prescribing and incorporating utilization data to inspire new quality and safety initiatives. Further studies are needed to assess the impact on antimicrobial utilization, infection control measures, and patient care outcomes.

Antimicrobial utilization in an Iraqi province: a comprehensive evaluation of antibiotic source and cost.

PURPOSE: The aims were to calculate total systemic antibiotic consumption and cost in both public and private sectors in all care settings in Al-Najaf province, Iraq, during 2012, recognize the percentage of each pharmacological class for the dispensed antibiotics and identify oral and parenteral antibiotic percentages dispensed and the portions manufactured nationally and imported. METHODS: Cross-sectional study was conducted in Al-Najaf to calculate the total cost and quantities of antibiotics consumed during 2012 using World Health Organization Guidelines for Defined Daily Dose (DDD). KEY FINDINGS: The results showed more than 21 million DDDs were dispensed in Al-Najaf in one year, and more than half (54.2%) were dispensed by governmental healthcare institutions. A thousand inhabitants in the province consumed 45.26 DDDs per day. Extended-spectrum (34.49%) and combined penicillins (26.08%) were the most frequently consumed while meropenem was the least frequently consumed (0.02%). Ninety-five per cent of the consumed antibiotics were oral dosage forms, and five per cent were parenteral dosage forms. The total cost of antibiotic consumed was more than nine million U.S dollars. CONCLUSIONS: The antibiotic consumption ratio in this province was comparable to neighbouring countries, but far higher compared to European countries. Penicillins, cephalosporins and quinolones were the most popular antibiotics. Around half of the antibiotics consumed were made by national pharmaceutical companies that mainly produce oral antibiotics. The public sector consumed a higher portion, but spent a lower amount compared to private sectors. This is the first time report of antibiotic consumption in Iraq. More studies evaluating antibiotic consumption can improve utilization.

Antimicrobial use control measures to prevent and control antimicrobial resistance in US hospitals.

OBJECTIVE: Clinical practice guidelines and recommended practices to control use of antibiotics have been published, but the effect of these practices on antimicrobial resistance (AMR) rates in hospitals is unknown. The objective of this study was to examine relationships between antimicrobial use control strategies and AMR rates in a national sample of US hospitals. DESIGN: Cross-sectional, stratified study of a nationally representative sample of US hospitals. METHODS: A survey instrument was sent to the person responsible for infection control at a sample of 670 US hospitals. The outcome was current prevalences of 4 epidemiologically important, drug-resistant pathogens, considered concurrently: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, ceftazidime-resistant Klebsiella species, and quinolone (ciprofloxacin)-resistant Escherichia coli. Five independent variables regarding hospital practices were selected from the survey: the extent to which hospitals (1) implement practices recommended in clinical practice guidelines and ensure best practices for antimicrobial use, (2) disseminate information on clinical practice guidelines for antimicrobial use, (3) use antimicrobial-related information technology, (4) use decision support tools, and (5) communicate to prescribers about antimicrobial use. Control variables included the hospitals' number of beds, teaching status, Veterans Affairs status, geographic region, and number of long-term care beds; and the presence of an intensive care unit, a burn unit, or transplant services. A generalized estimating equation modeled all resistance rates simultaneously to identify overall predictors of AMR levels at the facility. RESULTS: Completed survey instruments were returned by 448 hospitals (67%). Four antimicrobial control measures were associated with higher prevalence of AMR. Implementation of recommended practices for antimicrobial use (P < .01) and optimization of the duration of empirical antibiotic prophylaxis (P < .01) were associated with a lower prevalence of AMR. Use of restrictive formularies (P = .05) and dissemination of clinical practice guideline information (P < .01) were associated with higher prevalence of AMR. Number of beds and Veterans Affairs status were also associated with higher AMR rates overall. CONCLUSIONS: Implementation of guideline-recommended practices to control antimicrobial use and optimize the duration of empirical therapy appears to help control AMR rates in US hospitals. A longitudinal study would confirm the results of this cross-sectional study. These results highlight the need for systems interventions and reengineering to ensure more-consistent application of guideline-recommended measures for antimicrobial use.

Development of a medication monitoring attitude measure using a mixed methods item development process.

OBJECTIVES: Medication monitoring is important for safe and effective medication use; however, no attitudinal measure exists for a health care provider's medication monitoring attitude. The objectives of this study were to (1) create a measure of a community pharmacist medication monitoring attitude; (2) test concurrent validity using a validated measure of medication monitoring behaviours; and (3) report community pharmacist attitudes towards medication monitoring. METHODS: A mixed methods item development process was employed to generate Likert-type items from qualitative interviews. Following item review and piloting, a four-contact survey, including 20 6-point Likert-type items and the four-item Behavioral Pharmaceutical Care Scale monitoring domain, was mailed to 599 randomly sampled US community pharmacists from the state of Iowa. Exploratory factor analysis, Pearson's correlation and descriptive statistics were used to address study objectives. KEY FINDINGS: There were 254 (42.4%) returned and usable surveys. Factor analysis yielded two domains, a seven-item, positively worded internal (α = 0.819) and an eight-item, negatively worded external domain (α = 0.811). Both domains were positively correlated with the monitoring domain of the Behavioral Pharmaceutical Care Scale supporting convergent validity. Overall, respondents had a positive internal monitoring attitude with a mean of 4.62 (0.68), although many practiced in an environment less conducive to monitoring, as evident by a mean of 3.13 (0.88). Pharmacists were more oriented towards medication side effect and effectiveness monitoring than nonadherence monitoring. CONCLUSIONS: The mixed methods item development process created a reliable and valid measure of a pharmacist's medication monitoring attitude. While pharmacists had an overall positive medication monitoring attitude, improvements are needed to bolster adherence monitoring and make pharmacy environments more conducive to monitoring.

Importance of control group selection for evaluating antimicrobial use as a risk factor for methicillin-resistant Staphylococcus aureus bacteremia.

OBJECTIVE: We investigated the importance of control group selection during an evaluation of antimicrobial use as a risk factor for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia at our institution. METHODS: We performed a case-control study. A case was defined as any patient admitted between January 1997 and May 2001 who developed nosocomial MRSA bacteremia. We used two control groups; control group I consisted of patients with nosocomial methicillin-susceptible S. aureus (MSSA) bacteremia and control group II included only patients without bacteremia. We matched control-patients to case-patients using age, gender, time at risk, and hospital ward. Data collected on all patients included demographics, comorbidities, antibiotic use, time at risk, length of stay, severity of illness, and outcome. RESULTS: We evaluated 63 patients (21 in each group). The three groups were well matched regarding age, gender, underlying diseases, and severity of illness. Patients in the MRSA group were more likely to have received a fluoroquinolone and had a higher mean number of days of fluoroquinolone use than did patients in the MSSA group (P = .027 and P = .015, respectively). However, all measures of fluoroquinolone use were similar for case-patients and for control-patients who did not have nosocomial bloodstream infection. CONCLUSIONS: Control group selection is important in evaluating antimicrobial use as a risk factor for MRSA bacteremia. Using control-patients infected with MSSA, rather than uninfected control-patients, may overestimate the association between antimicrobial use and MRSA infection.

Variation in the use of procedures to monitor antimicrobial resistance in U.S. hospitals.

BACKGROUND: Antimicrobial resistance is a growing clinical and public health crisis. Experts have recommended measures to monitor antimicrobial resistance; however, little is known regarding their use. OBJECTIVE: We describe the use of procedures to detect and report antimicrobial resistance in U.S. hospitals and the organizational and epidemiologic factors associated with their use. METHODS: In 2001, we surveyed laboratory directors (n = 108) from a random national sample of hospitals. We studied five procedures to monitor antimicrobial resistance: (1) disseminating antibiograms to physicians at least annually, (2) notifying physicians of antimicrobial-resistant infections, (3) reporting susceptibility results within 24 hours, (4) using automated testing procedures, and (5) offering molecular typing. Explanatory variables included organizational characteristics and patterns of antimicrobial resistance for oxacillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, quinolone-resistant Escherichia coli, and extended-spectrum beta-lactamase-producing Klebsiella species. Generalized estimating equations accounting for the correlation among outcomes at the facility level were used to identify predictors of the five outcomes. RESULTS: Use of the procedures ranged from 85% (automated testing) to 33% (offering molecular typing) and was related to teaching hospital status (OR, 3.1; CI95, 1.5-6.5), participation of laboratory directors on the infection control committee (OR, 1.7; CI95, 1.1-2.8), and having at least one antimicrobial-resistant pathogen with a prevalence greater than 10% (OR, 2.2; CI95, 1.4-3.3). CONCLUSION: U.S. hospitals underutilize procedures to monitor the spread of antimicrobial resistance. Use of these procedures varies and is related to organizational and epidemiologic factors. Further efforts are needed to increase their use by hospitals.

Women's quality of life is decreased by acute cystitis and antibiotic adverse effects associated with treatment.

BACKGROUND: Although acute cystitis is a common infection in women, the impact of this infection and its treatment on women's quality of life (QOL) has not been previously described. OBJECTIVES: To evaluate QOL in women treated for acute cystitis, and describe the relationship between QOL, clinical outcome and adverse events of each of the interventions used in the study. DESIGN: Randomized, open-label, multicenter, treatment study. SETTING: Two family medicine outpatient clinics in Iowa. PATIENTS: One-hundred-fifty-seven women with clinical signs and symptoms of acute uncomplicated cystitis. INTERVENTION: Fifty-two patients received trimethoprim/sulfamethoxazole 1 double-strength tablet twice daily for 3 days, 54 patients received ciprofloxacin 250 mg twice daily for 3 days and 51 patients received nitrofurantoin 100 mg twice daily for 7 days. MEASUREMENTS: QOL was assessed at the time of enrollment and at 3, 7, 14 and 28 days after the initial visit. QOL was measured using a modified Quality of Well-Being scale, a validated, multi-attribute health scale. Clinical outcome was assessed by telephone interview on days 3, 7, 14 and 28 using a standardized questionnaire to assess resolution of symptoms, compliance with the prescribed regimen, and occurrence of adverse events. RESULTS: Patients experiencing a clinical cure had significantly better QOL at days 3 (p = 0.03), 7 (p < 0.001), and 14 (p = 0.02) compared to patients who failed treatment. While there was no difference in QOL by treatment assignment, patients experiencing an adverse event had lower QOL throughout the study period. Patients treated with ciprofloxacin appeared to experience adverse events at a higher rate (62%) compared to those treated with TMP/SMX (45%) and nitrofurantoin (49%), however the difference was not statistically significant (p = 0.2). CONCLUSION: Patients experiencing cystitis have an increase in their QOL with treatment. Those experiencing clinical cure have greater improvement in QOL compared to patients fail therapy. While QOL is improved by treatment, those reporting adverse events have lower overall QOL compared to those who do not experience adverse events. This study is important in that it suggests that both cystitis and antibiotic treatment can affect QOL in a measurable way.

Susceptibility testing methods of antifungal agents.

Several methods for testing antifungal susceptibility are currently utilized. Minimum inhibitory concentrations can be tested using standardized noncommercial or commercial tests. Fungicidal testing includes either in vitro methods, such as time-kill or minimum fungicidal testing methods, or animal models. This chapter provides background information for utilizing and evaluating results obtained from antifungal susceptibility testing methods.

Antimicrobial resistance trends and outbreak frequency in United States hospitals.

We assessed resistance rates and trends for important antimicrobial-resistant pathogens (oxacillin-resistant Staphylococcus aureus [ORSA], vancomycin-resistant Enterococcus species [VRE], ceftazidime-resistant Klebsiella species [K-ESBL], and ciprofloxacin-resistant Escherichia coli [QREC]), the frequency of outbreaks of infection with these resistant pathogens, and the measures taken to control resistance in a stratified national sample of 670 hospitals. Four hundred ninety-four (74%) of 670 surveys were returned. Resistance rates were highest for ORSA (36%), followed by VRE (10%), QREC (6%), and K-ESBL (5%). Two-thirds of hospitals reported increasing ORSA rates, whereas only 4% reported decreasing rates, and 24% reported ORSA outbreaks within the previous year. Most hospitals (87%) reported having implemented measures to rapidly detect resistance, but only approximately 50% reported having provided appropriate resources for antimicrobial resistance prevention (53%) or having implemented antimicrobial use guidelines (60%). The most common resistant pathogen in US hospitals is ORSA, which accounts for many recognized outbreaks and is increasing in frequency in most facilities. Current practices to prevent and control antimicrobial resistance are inadequate.

Antifungal activities of fluconazole, caspofungin (MK0991), and anidulafungin (LY 303366) alone and in combination against Candida spp. and Crytococcus neoformans via time-kill methods.

The activities of the echinocandins caspofungin and anidulafungin were evaluated alone and in combination with fluconazole using time-kill methods against isolates of Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, and Cryptococcus neoformans. Antifungal concentrations tested against each isolate were 0.5 microg/mL and 20 microg/mL of fluconazole and 0.007 microg/mL and 2 microg/mL of both caspofungin and anidulafungin. In addition, 20 microg/mL of fluconazole was tested with 2 microg/mL of caspofungin and anidulafungin to test for additive or antagonistic activity. Finally 0.5 microg/mL of fluconazole was tested with 0.007 microg/mL of caspofungin and anidulafungin to test for synergy. Combinations of fluconazole and caspofungin or anidulafungin resulted in indifference. Azole-echinocandin combinations do not produce antagonistic effects; therefore, combinations of these agents may warrant future clinical evaluation.

Are United States hospitals following national guidelines for the analysis and presentation of cumulative antimicrobial susceptibility data?

The National Committee for Clinical Laboratory Standards recently published guidelines for analysis and presentation of cumulative antimicrobial susceptibility test data (antibiograms). We sought to determine how well US hospitals already adhere to standards for antibiogram compilation, and to examine the relationship between hospital characteristics and guideline adherence. We surveyed laboratory directors at 670 hospitals and examined 3 guideline criteria: compilation of an antibiogram, annual updating, and distribution to infection control staff and medical staff yearly; 494 surveys were returned (74%). Almost all of the hospitals surveyed publish an antibiogram (95%, n = 481); however, only 60% (n = 296) met all three criteria. Hospital laboratories meeting criteria were more likely to serve as referral laboratories (OR = 1.82; 95% CI = 1.26-2.63), perform susceptibility testing on site (OR = 4.47; 95% CI = 1.84-10.84), use confirmatory tests to detect extended-spectrum beta-lactamases (OR = 1.8; 95% CI = 1.2-2.6), and have more laboratory personnel per bed (3.0 vs. 2.0 FTEs/bed, p = 0.0031). Adherence to guidelines for preparation and dissemination of antibiograms could be improved. Institutional commitment to high quality, on-site microbiology laboratory services will improve adherence to these guidelines.