A US-based national surveillance study for the susceptibility and epidemiology of Clostridioides difficile isolates with special reference to ridinilazole: 2020-2021.

We have previously reported on the susceptibility and epidemiology of Clostridioides difficile isolates from six geographically dispersed medical centers in the United States. This current survey was conducted with isolates collected in 2020-2021 from six geographically dispersed medical centers in the United States, with specific attention to susceptibility to ridinilazole as well as nine comparators. C. difficile isolates or stools from patients with C. difficile antibiotic-associated diarrhea were collected and referred to a central laboratory. After species confirmation of 300 isolates at the central laboratory, antibiotic susceptibilities were determined by the agar dilution method [M11-A9, Clinical and Laboratory Standards Institute (CLSI)] against the 10 agents. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Ridinilazole had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL, and no isolate had an MIC greater than 0.5 mcg/mL. In comparison, fidaxomicin had an MIC 90 of 0.5 mcg/mL. The vancomycin MIC 90 was 2 mcg/mL with a 0.7% resistance rate [both CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria]. The metronidazole MIC 90 was 1 mcg/mL, with none resistant by CLSI criteria, and a 0.3% resistance rate by EUCAST criteria. Among the 50 different ribotypes isolated in the survey, the most common ribotype was 014-020 (14.0%) followed by 106 (10.3%), 027 (10%), 002 (8%), and 078-126 (4.3%). Ridinilazole maintained activity against all ribotypes and all strains resistant to any other agent tested. Ridinilazole showed excellent in vitro activity against C. difficile isolates collected between 2020 and 2021 in the United States, independent of ribotype.

Colitis caused by Clostridioides difficile infection in a domestic dog: A case report.

Clostridioides difficile has been identified as one of the primary etiologic agents of nosocomial diarrhea and pseudomembranous colitis in humans and other mammals associated following broad-spectrum antibiotics use. In Rio de Janeiro, Brazil we describe a case of C. difficile infection (CDI) in a 13-year-old male dog.

Clostridioides difficile ribotype 106: A systematic review of the antimicrobial susceptibility, genetics, and clinical outcomes of this common worldwide strain.

Clostridioides difficile typing is invaluable for the investigation of both institution-specific outbreaks as well as national surveillance. While the epidemic ribotype 027 (RT027) has received a significant amount of resources and attention, ribotype 106 (RT106) has become more prevalent throughout the past decade. The purpose of this systematic review was to comprehensively summarize the genetic determinants, antimicrobial susceptibility, epidemiology, and clinical outcomes of infection caused by RT106. A total of 68 articles published between 1999 and 2019 were identified as relevant to this review. Although initially identified in the United Kingdom in 1999, RT106 is now found worldwide and became the most prevalent strain in the United States in 2016. Current data indicate that RT106 harbors the tcdA and tcdB genes, lacks binary toxin genes, and does not contain any deletions in the tcdC gene, which differentiates it from other epidemic strains, including ribotypes 027 and 078. Interestingly, RT106 produces more spores than other strains, including RT027. Overall, RT106 is highly resistant to erythromycin, clindamycin, fluoroquinolones, and third-generation cephalosporins. However, the MIC90 in most studies are one to two fold dilutions below the epidemiologic cut-off values of metronidazole and vancomycin, suggesting both are acceptable treatment options from an in vitro perspective. The few clinical outcomes studies available concluded that RT106 causes less severe disease than RT027, but patients were significantly more likely to experience multiple CDI relapses when infected with a RT106 strain. Specific areas warranting future study include potential survival advantages provided by genetic elements as well as a more robust investigation of clinical outcomes associated with RT106.

Characterization of Clostridioides difficile ribotypes in domestic dogs in Rio de Janeiro, Brazil.

Clostridioides difficile is the major etiologic agent of nosocomial bacterial diarrhoea and pseudomembranous colitis. The pathogenesis of C. difficile infection (CDI)involves two cytotoxic enzymes (TcdA, TcdB) that cause colonic epithelial damage, fluid accumulation and enteritis. CDI has been demonstrated in a variety of animal species and some reports have recently raised the importance of wild animals as a reservoir of this pathogen and possible transmission to humans and domestic animals. The aim of this study was to characterize C. difficile isolates obtained from pet dogs in Rio de Janeiro, Brazil. A total of 50 faecal samples were obtained from healthy and diarrheic dogs. Five of fifty samples (10%) grew C. difficile. Of those, three belonged to the PCR ribotype 106 (ST 42) and were toxigenic (A+B+). The other two strains belonged to the PCR ribotype 010 (ST 15) and were not toxin producers (A-B-). None of the isolates tested positive for the binary toxin genes. Considering the antimicrobial resistance patterns of all isolates using EUCAST breakpoints, all strains were sensitive to metronidazole and vancomycin. However, two strains (ribotype 106 and ribotype 010), were resistant to clindamycin (≤256 µg/mL). All strains were strong biofilm producers. Our study provides evidence that dogs can act as reservoirs for C. difficile epidemic ribotypes.

Mechanisms for floor surfaces or environmental ground contamination to cause human infection: a systematic review.

Shoe soles have been shown to transfer infectious microorganisms to floor and ground surfaces. However, the possible modes of transmission of infectious agents from floors or ground surfaces to human contact for infection have not been systematically reviewed. A systematic review was performed on articles indexed in medical databases (Medline, EMBASE, PubMed) using a pre-defined search strategy and MeSH terms (date of last search: 15 March 2016). Only primary research studies in English that investigated the transmission dynamics of infectious microorganisms from floor or ground surfaces to human infection were included. Extraction of articles was performed two independent reviewers using pre-defined data fields in an Excel sheet. Disagreements were resolved by consensus. Thirty studies met the inclusion criteria. Almost all hospital-associated microorganisms including methicillin-resistant Staphylococcus aureus, Clostridium difficile, and multidrug-resistant Gram-negative species were identified on floor or ground surfaces. Several modes of transmission dynamics, most commonly direct contact or aerosolization, were identified. In conclusion, interventions such as efficient cleaning of floor surfaces and vectors that transfer infectious organisms to floors such as shoe soles could be an effective infection control strategy to prevent human disease.

Epidemiology of meningitis with a negative CSF Gram stain: under-utilization of available diagnostic tests.

Meningitis with a negative cerebrospinal fluid Gram stain (CSF-GS) poses a diagnostic challenge as more than 50% of patients remain without an aetiology. The introduction of polymerase chain reaction (PCR) and arboviral serologies have increased diagnostic capabilities, yet large scale epidemiological studies evaluating their use in clinical practice are lacking. We conducted a prospective observational study in New Orleans between November 1999 and September 2008 (early era) when PCR was not widely available, and in Houston between November 2008 and June 2013 (modern era), when PCR was commonly used. Patients presenting with meningitis and negative CSF-GS were followed for 4 weeks. All investigations, PCR used, and results were recorded as they became available. In 323 patients enrolled, PCR provided the highest diagnostic yield (24·2%) but was ordered for 128 (39·6%) patients; followed by serology for arboviruses (15%) that was ordered for 100 (31%) of all patients. The yield of blood cultures was (10·3%) and that of CSF cultures was 4%; the yield for all other tests was <10%. Overall, 65% of the patients remained without a diagnosis at 4 weeks: 72·1% in early era vs. 53·4% (P < 0·01) in modern era; this change was attributed to diagnosing more viral pathogens, 8·3% and 26·3% (P < 0·01), respectively. The introduction of PCR and arboviral serologies has improved the yield of diagnosing patients with meningitis and a negative CSF-GS, but both tests are being under-utilized.

Shoe soles as a potential vector for pathogen transmission: a systematic review.

Shoe soles are possible vectors for infectious diseases. Although studies have been performed to assess the prevalence of infectious pathogens on shoe soles and decontamination techniques, no systematic review has ever occurred. The aim of this study was to perform a systematic review of the literature to determine the prevalence of infectious agents on shoe bottoms and possible decontamination strategies. Three electronic bibliographic databases were searched using a predefined search strategy evaluating prevalence of infectious pathogens on shoe bottoms and decontamination strategies. Quality assessment was performed independently by two reviews with disagreements resolved by consensus. Thirteen studies were identified that supported the hypothesis that shoe soles are a vector for infectious pathogens. Methicillin-resistant Staphylococcus aureus, Clostridium difficile and multidrug-resistant Gram-negative species among other pathogens were documented on shoe bottoms in the health care setting, in the community and among food workers. Fifteen studies were identified that investigated decontamination strategies for shoe soles. A number of decontamination strategies have been studied of which none have been shown to be consistently successful at disinfecting shoe soles. In conclusion, a high prevalence of microbiological pathogens was identified from shoe soles studied in the health care, community and animal worker setting. An effective decontamination strategy for shoe soles was not identified. Studies are needed to assess the potential for contaminated shoes to contribute to the transmission of infectious pathogens.

Evaluation of antifungal therapy in patients with candidaemia based on susceptibility testing results: implications for antimicrobial stewardship programmes.

BACKGROUND: Definitive antifungal therapy is typically based on Candida species and clinical status, rather than susceptibility reports. Antifungal susceptibility testing is available, but the impact on treatment decisions is unknown. The purpose of this study was to assess antifungal therapy in hospitalized patients with candidaemia during the time period between the start of empirical therapy and after antifungal susceptibility testing reports are available. METHODS: A retrospective study of 161 hospitalized patients with candidaemia was conducted. Patients who received fluconazole or an echinocandin were evaluated for changes in empirical antifungal therapy prior to and after susceptibility reporting. RESULTS: One hundred and sixty-one patients aged 59 ±â€Š16 years (male, 54%; Caucasian, 52%; APACHE II score ≥ 15, 48%; and intensive care unit, 50%) were identified, of whom 130 (81%) had fluconazole-susceptible candidaemia. Fifty-eight patients (36%) were initiated on fluconazole and 103 (64%) on an echinocandin. The mean time from culture to the susceptibility report was 5 ±â€Š2 days. Prior to availability of the susceptibility report, 20 fluconazole-initiated patients (34%) were switched to an echinocandin, while 14 echinocandin-initiated patients (14%) were switched to fluconazole. Once a susceptibility report was available, 35 of 89 (39%) patients with fluconazole-susceptible candidaemia on an echinocandin were de-escalated to fluconazole. Eleven patients on fluconazole just prior to a susceptibility report were identified with a fluconazole-resistant Candida species. CONCLUSIONS: Using antifungal susceptibility testing, patients given fluconazole with fluconazole-resistant Candida species were identified. Less than 40% of echinocandin-treated patients with fluconazole-susceptible organisms were de-escalated to fluconazole. Antifungal susceptibility testing may help to identify patients in need of clinical intervention.

Meta-analysis to assess risk factors for recurrent Clostridium difficile infection.

SUMMARY: Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhoea. It is estimated that 15-20% of patients experience recurrence of CDI. A limited number of studies have looked at the risk factors for recurrent CDI. We conducted a meta-analysis of observational studies and randomised controlled trials (RCTs) to assess risk factors for recurrent CDI. Studies were identified using the PubMed database and search terms 'Clostridium difficile associated diarrhoea' or 'pseudomembranous colitis'. Both observational studies and RCTs were included. In all, 1215 studies were identified of which 48 met the inclusion criteria. Twelve studies involving 1382 patients with CDI met the complete eligibility requirements. Odds ratios and information on study quality were abstracted by two investigators independently. To be included in the analysis, each risk factor was required to be evaluated by at least three separate studies. Continued use of non-C. difficile antibiotics after diagnosis of CDI (OR: 4.23; 95% CI: 2.10-8.55; P<0.001), concomitant receipt of antacid medications (OR: 2.15; 95% CI: 1.13-4.08; P=0.019), and older age (OR: 1.62; 95% CI: 1.11-2.36; P=0.0012) were significantly associated with increased risk of recurrent CDI. Significant prognostic risk factors were identified as risk factors for CDI recurrence. Additional or novel interventions may be required for these patients to prevent CDI recurrence.

A clinical risk index for Clostridium difficile infection in hospitalised patients receiving broad-spectrum antibiotics.

Identification of a population at high risk for Clostridium difficile infection (CDI) would enable CDI prevention strategies to be designed. The purpose of this study was to create a clinical risk index that would predict those at risk for CDI. A CDI risk index was therefore developed, based on a cohort of hospital patients given broad-spectrum antibiotics, and divided into a development and validation cohort. Logistic regression equations helped identify significant predictors of CDI. A scoring algorithm for CDI risk was created using identified risk factors and collapsed to create four categories of CDI risk. The area under the receiver operating characteristic (aROC) curve was used to measure goodness-of-fit. Among 54 226 patients, 392 tested positive for C. difficile. Age 50-80 years [odds ratio (OR: 0.5; P<0.0116)], age >80 years (OR: 2.5; P<0.0001), haemodialysis (OR: 1.5; P=0.0227), non-surgical admission (OR: 2.2; P<0.0001) and increasing length of stay in the intensive care unit (OR: 2.1; P<0.0001) were significantly associated with CDI. A simple risk index using presence of significant variables was significantly associated with increasing risk for CDI in both development (OR: 3.57; P<0.001; aROC: 0.733) and validation (OR: 3.31; P<0.001; aROC: 0.712) cohorts. An OR-derived risk index did not perform as well as the simple risk index. This easily implemented risk index should allow stratification of patients into risk group categories for development of CDI and help fashion preventive strategies.

Multicentre derivation and validation of a simple predictive index for healthcare-associated Clostridium difficile infection.

OBJECTIVES: Clostridium difficile infection (CDI) is the most common cause of healthcare-associated infections in the United States. Despite well-established risk factors, little research has focused on use of these variables to identify a patient population at high risk for CDI to target with primary prevention strategies. A predictive index for healthcare-associated CDI could improve clinical care and guide research for primary prevention trials. Our objective was to develop a predictive index to identify patients at high risk for healthcare-associated CDI. METHODS: We performed a secondary database analysis in a five-hospital health system in Houston, Texas. Our cohort consisted of 97 130 hospitalized patients admitted for more than 48 hours between October 2014 and September 2016. The derivation cohort consisted of the initial 80% of admissions (75 545 patients), with the remainder being used in the validation cohort. RESULTS: CDI rates in the derivation and validation cohorts were 1.55% and 1.43%, respectively. Thirty-day predictors of CDI were increased number of high-risk antibiotics, Charlson comorbidity index score, age and receipt of a proton pump inhibitor. These variables were incorporated into a simple risk index with a score range of 0 to 10. The final model demonstrated good discrimination and calibration with the observed CDI incidence ranging from 0.1% to 20.4%. CONCLUSIONS: We developed a predictive index for 30-day risk of healthcare-associated CDI using readily available and clinically useful variables. This simple predictive risk index may be used to improve clinical decision making and resource allocation for CDI stewardship initiatives, and guide research design.

Evaluation of a shoe sole UVC device to reduce pathogen colonization on floors, surfaces and patients.

BACKGROUND: An ultraviolet C (UVC) decontamination device that delivers germicidal UVC radiation to the soles of shoes has become available recently. AIM: To demonstrate that shoe soles can be vectors for healthcare-associated infection, and to investigate if a UVC shoe sole decontamination device would decrease this risk effectively. METHODOLOGY: Three bacterial strains (Staphylococcus aureus, Enterococcus faecalis and Escherichia coli) and a non-toxigenic strain of Clostridium difficile were spiked on to standardized rubber-soled shoe soles and then selected at random for UVC exposure or no UVC exposure. Experiments were performed to test the efficacy of the UVC device to decontaminate shoe soles and flooring. E. faecalis was spiked on to shoes to assess colonization of a simulated healthcare environment and patient. RESULTS: The UVC device decreased shoe sole contamination significantly for all tested bacterial species, and decreased floor contamination significantly for all floor types and species tested (P<0.01 for all experiments). The log10 reduction was the highest for E. coli (mean±standard deviation 2.6±0.79), followed by E. faecalis (2.19±0.68), S. aureus (1.74±0.88) and C. difficile (0.42±0.54) (P<0.0001 for all analyses). Exposure of shoe soles to the UVC device decreased contamination significantly (mean log10 reduction 2.79±1.25; P<0.0001). Proportions of samples from furniture, bed and patient dummy samples decreased from 96-100% positive in controls to 5-8% positive in UVC device experiments (P<0.0001 for all analyses). CONCLUSION: A UVC decontamination device was shown to reduce the colony-forming unit counts of relevant pathogenic organisms from shoe soles with subsequent decreased colonization of floors, healthcare equipment, furniture, beds and a patient dummy.

Prevalence of AmpC over-expression in bloodstream isolates of Pseudomonas aeruginosa.

This study examined the contribution of AmpC over-expression to beta-lactam resistance in clinical isolates of Pseudomonas aeruginosa obtained from a hospital in Houston, TX, USA. Seventy-six non-repeat bloodstream isolates obtained during 2003 were screened for ceftazidime resistance in the presence and absence of clavulanic acid 4 mg/L. AmpC was identified by isoelectric focusing (with and without cloxacillin inhibition); stable derepression was ascertained phenotypically by a spectrophotometric assay (with and without preceding induction by imipenem) using nitrocefin as the substrate, and was confirmed subsequently by quantitative RT-PCR of the ampC gene. The clonal relatedness of the AmpC-over-expressing isolates was assessed by pulsed-field gel electrophoresis. In addition, the ampC and ampR gene sequences were determined by PCR and sequencing. For comparison, two standard wild-type strains (PAO1 and ATCC 27853) and three multidrug-susceptible isolates were used as controls. AmpC over-expression was confirmed in 14 ceftazidime-resistant isolates (overall prevalence rate, 18.4%), belonging to seven distinct clones. The most prevalent point mutations in ampC were G27D, V205L and G391A. Point mutations in ampR were also detected in eight ceftazidime-resistant isolates. AmpC over-expression appears to be a significant mechanism of beta-lactam resistance in P. aeruginosa. Understanding the prevalence and mechanisms of beta-lactam resistance in P. aeruginosa may guide the choice of empirical therapy for nosocomial infections in hospitals.

Epidemiology and incidence of Clostridium difficile-associated diarrhoea diagnosed upon admission to a university hospital.

Patients with Clostridium difficile-associated diarrhoea (CDAD) may initially develop symptoms in the community and be subsequently diagnosed at hospital admission. At the present time there is no national surveillance system and no standardized case definition of CDAD in the USA, and baseline data on the incidence and epidemiology of CDAD are scarce. The objective of this study was to report the incidence of CDAD at a tertiary care hospital, and to determine the epidemiology of cases diagnosed within 48h of hospital admission, compared with cases of nosocomial CDAD diagnosed 48h or more after hospitalization. The average incidence was 4.0 cases/10 000 patient-days for CDAD on admission and 7.0 cases/10 000 patient-days for nosocomial CDAD. A significant difference was observed in CDAD rates on admission compared with nosocomial CDAD rates (P=0.017), but no differences were observed over time for either rate. Overall, 44% of cases had CDAD on admission and 56% of cases had nosocomial CDAD. Fifty-six (62%) patients with CDAD on admission had been admitted to the same hospital and 24 (27%) had been admitted to another hospital within the previous 90 days. Only eight (9%) patients had not been exposed to any healthcare services in the 90 days preceding hospital admission. A standardized case definition of healthcare-associated CDAD should include previous hospitalizations. Admitting physicians should consider C. difficile in the differential diagnosis of patients admitted with diarrhoea, with or without a history of admission to healthcare facilities.

Risk factors for postoperative chest wound infections due to gram-negative bacteria in cardiac surgery patients.

Gram-negative bacteria account for up to 35% of postoperative sternal wound infections (SWI) in patients undergoing cardiac surgery. Despite this, risk factors for Gram-negative SWI have not been investigated. The objective of this study was to define risk factors associated with Gram-negative SWI in patients undergoing cardiac surgery. 2590 patients undergoing cardiac surgery between 2002-2005 were prospectively monitored for development of SWI. Patient, operative, and post-operative risk factors were compared among patients that developed Gram-negative SWI and Gram-positive SWI to uninfected controls using univariate and multivariate analysis. A p < 0.05 was considered significant. Surgical site infections developed in 152 (5.9%) patients. Isolates were recovered from the sternum for 128 (5.0%) patients, from the leg donor site for 19 (0.73%) patients, and from the sternum and donor site for 5 (0.19%) patients. Gram-positive pathogens were isolated from 83 (3.3%) patients, Gram-negative pathogens from 42 (1.6%) patients, and mixed pathogens from 27 (1.0%) patients. Hospital admission greater than 48 hours before surgery (OR: 2.25; 95% CI: 1.11 - 4.58), ventilator-dependency preoperatively (OR: 5.32 95% CI: 2.22 - 12.75), and thoracentesis procedure postoperatively (OR: 3.71; 95% CI: 1.45 - 9.49) and diabetes (OR: 2.04; 95% CI: 1.17 - 3.55) were identified as significant risk factors for SWI due to Gram-negative bacteria using multivariate logistic regression. Diabetes, increased age, and peripheral vascular disease were identified as significant risk factors for SWI due to Gram-positive bacteria (p < 0.05, each). The risk factors associated with Gram-negative SWI differed significantly from those associated with Gram-positive SWI. Risk factors associated with Gram-negative SWI were identified. Unique interventions may be necessary to prevent Gram-negative SWI in cardiac surgery patients.

Economic burden of primary compared with recurrent Clostridium difficile infection in hospitalized patients: a prospective cohort study.

BACKGROUND: Few studies have investigated the additional healthcare costs of recurrent C. difficile infection (CDI). AIM: To quantify inpatient treatment costs for CDI and length of stay among hospitalized patients with primary CDI only, compared with CDI patients who experienced recurrent CDI. METHODS: This was a prospective, observational cohort study of hospitalized adult patients with primary CDI followed for three months to assess for recurrent CDI episodes. Total and CDI-attributable hospital length of stay (LOS) and hospitalization costs were compared among patients who did or did not experience at least one recurrent CDI episode. FINDINGS: In all, 540 hospitalized patients aged 62±17 years (42% males) with primary CDI were enrolled, of whom 95 patients (18%) experienced 101 recurrent CDI episodes. CDI-attributable median (interquartile range) LOS and costs (in US$) increased from 7 (4-13) days and $13,168 (7,525-24,456) for patients with primary CDI only versus 15 (8-25) days and $28,218 (15,050-47,030) for patients with recurrent CDI (P<0.0001, each). Total hospital median LOS and costs increased from 11 (6-22) days and $20,693 (11,287-41,386) for patients with primary CDI only versus 24 (11-48) days and $45,148 (20,693-82,772) for patients with recurrent CDI (P<0.0001, each). The median cost of pharmacological treatment while hospitalized was $60 (23-200) for patients with primary CDI only (N=445) and $140 (30-260) for patients with recurrent CDI (P=0.0013). CONCLUSION: This study demonstrated that patients with CDI experience a significant healthcare economic burden attributed to CDI. Economic costs and healthcare burden increased significantly for patients with recurrent CDI.

Long-term clarithromycin decreases prednisone requirements in elderly patients with prednisone-dependent asthma.

Prolonged use of prednisone is associated with serious side effects, such as osteoporosis, particularly among elderly individuals. Macrolide antibiotics exhibit anti-inflammatory effects that are distinct from their antimicrobial properties. Thus, the purpose of this case report is to describe the effects of prolonged treatment with clarithromycin, 500 mg bid, in reducing prednisone requirements in three elderly patients with prednisone-dependent asthma. Three patients (one woman and two men) aged 63 to 69 years, who had been treated with 5 to 10 mg prednisone daily for at least the last 12 months, were given clarithromycin, 500 mg bid. They were followed regularly for changes in daily prednisone dose, spirometry, quality of life, and adverse events. The prednisone dose was tapered in a stepwise fashion at each clinic visit. Within 3 to 6 months of initiation of treatment with clarithromycin, and throughout the 12-month follow-up, two of three patients discontinued prednisone therapy, while the third patient displayed increased spirometry readings and noted an increasingly better quality of life. Pulmonary function tests were stable or improved over this time period, with no reported adverse events, including increased rate of infections. One patient relapsed upon discontinuation of clarithromycin therapy but has since responded to re-initiation of treatment. Long-term oral clarithromycin may have a role in reducing prednisone requirements in elderly patients with prednisone-dependent asthma.

Trovafloxacin: an overview.

Trovafloxacin, a new synthetic naphthyridine fluoroquinolone antibiotic, is a broad-spectrum agent available orally and intravenously. It was recently approved by the Food and Drug Administration for the treatment of selected pulmonary, surgical, intraabdominal, gynecologic, pelvic, skin, and urinary tract infections. Its spectrum of activity includes aerobic gram-positive and gram-negative organisms as well as anaerobic pathogens. It is rapidly absorbed after oral administration, achieves good tissue and cerebrospinal fluid penetration, and has a half-life that allows once-daily dosing. It is hepatically metabolized, and dosage adjustments are necessary for patients with severe hepatic dysfunction but not for those with mild or moderate dysfunction or renal dysfunction. The drug has a favorable safety profile, and a high tendency for transient first-dose dizziness and/or lightheadedness in young women. Similar to other quinolones, trovafloxacin should not be taken with antacids that contain aluminum or magnesium, sucralfate, or ferrous sulfate. Trovafloxacin may prove beneficial as it allows for oral or intravenous monotherapy against indicated infections that normally require multidrug, broad-spectrum antibiotic coverage.

Possible interaction between imipramine and butalbital.

A 44-year-old woman was admitted to the psychiatric unit for exacerbation of her depressive disorder. Blood concentrations of her antidepressant, imipramine, were within normal range and consistent with past concentrations. Her medical history was significant for a chronic headache disorder for which she was given a prescription containing butalbital on admission. The patient's depressive disorder was quickly controlled but relapsed 2 weeks later. Concentrations of imipramine showed a decrease of approximately 50%. Imipramine is metabolized in the liver by the cytochrome P-450 (CYP 1A2) system, and barbiturates are known inducers of this enzyme subset. To our knowledge, an interaction specifically between butalbital and imipramine has not been documented; however, these drugs are extensively prescribed and occasions may arise where they are given concurrently. We recommend repeat measurement of imipramine concentrations 1 week after the start of any butalbital-containing product or barbiturate, and dosage adjustments based on the results and on the patient's response to the change.

Telithromycin: an oral ketolide for respiratory infections.

The ketolides represent a new subclass of antibiotics among the macrolide-lincosamide-streptogramin group. Telithromycin, the first ketolide to be awarded approvable status for clinical use, demonstrates in vitro activity against community-acquired respiratory pathogens including penicillin- and erythromycin-resistant Streptococcus pneumoniae. An extended half-life permits once-daily oral administration. Telithromycin is a substrate for cytochrome P450 (CYP) 3A4 and also inhibits drugs metabolized by CYP3A4. A relatively high frequency of mild-to-moderate gastrointestinal adverse effects has been reported. Similar clinical and microbiologic efficacy has been demonstrated with oral dosing in comparative clinical trials for community-acquired pneumonia, acute sinusitis, acute exacerbations of chronic bronchitis, and pharyngitis. Although limited data on penicillin-resistant S. pneumoniae and erythromycin-resistant Streptococcus pyogenes are available from clinical trials, this drug appears promising for respiratory infections caused by these pathogens.