Multi-ancestry genome-wide analysis identifies shared genetic effects and common genetic variants for self-reported sleep duration.

Both short (≤6 h per night) and long sleep duration (≥9 h per night) are associated with increased risk of chronic diseases. Despite evidence linking habitual sleep duration and risk of disease, the genetic determinants of sleep duration in the general population are poorly understood, especially outside of European (EUR) populations. Here, we report that a polygenic score of 78 European ancestry sleep duration single-nucleotide polymorphisms (SNPs) is associated with sleep duration in an African (n = 7288; P = 0.003), an East Asian (n = 13 618; P = 6 × 10-4) and a South Asian (n = 7485; P = 0.025) genetic ancestry cohort, but not in a Hispanic/Latino cohort (n = 8726; P = 0.71). Furthermore, in a pan-ancestry (N = 483 235) meta-analysis of genome-wide association studies (GWAS) for habitual sleep duration, 73 loci are associated with genome-wide statistical significance. Follow-up of five loci (near HACD2, COG5, PRR12, SH3RF1 and KCNQ5) identified expression-quantitative trait loci for PRR12 and COG5 in brain tissues and pleiotropic associations with cardiovascular and neuropsychiatric traits. Overall, our results suggest that the genetic basis of sleep duration is at least partially shared across diverse ancestry groups.

Surotomycin versus vancomycin in adults with Clostridium difficile infection: primary clinical outcomes from the second pivotal, randomized, double-blind, Phase 3 trial.

BACKGROUND: The available treatment options for Clostridium difficile infection (CDI) are limited by high recurrence rates. Surotomycin was a novel bactericidal cyclic lipopeptide in development to treat CDI that demonstrated non-inferiority to vancomycin in a Phase 2 trial. OBJECTIVES: To assess surotomycin safety and clinical response (non-inferiority versus vancomycin) at the end of treatment (EOT) of CDI. Additionally, to assess surotomycin response over time and sustained response at 30-40 days post-EOT (superiority versus vancomycin). PATIENTS AND METHODS: Patients with CDI were randomized (1:1) to receive twice-daily oral surotomycin 250 mg alternating with twice-daily placebo or four-times-daily oral vancomycin 125 mg for 10 days in this Phase 3, double-blind, multicentre, international trial. Clinical response over time and sustained clinical response were monitored until the end of the trial, through a follow-up period of 30-40 days. Clinical Trial Registration: NCT01598311. RESULTS: A total of 285 and 292 patients with confirmed CDI were randomized to receive surotomycin and vancomycin, respectively. Surotomycin-associated clinical response at EOT was non-inferior to vancomycin (surotomycin/vancomycin: 83.4%/82.1%; difference 1.4%, 95% CI - 4.9, 7.6). Following treatment with surotomycin, both clinical response over time (stratified log-rank test, P = 0.277) and sustained clinical response (63.3%/59.0%; difference 4.3%, 95% CI - 3.6, 12.2) did not demonstrate superiority versus vancomycin at end of trial. Both treatments were generally well tolerated. CONCLUSIONS: Surotomycin demonstrated non-inferiority to vancomycin for CDI clinical response at EOT. Surotomycin did not demonstrate superiority to vancomycin for clinical response over time or sustained clinical response rate.

Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection.

OBJECTIVES: The aim of this study was to evaluate the susceptibilities of Clostridium difficile isolates to cadazolid, a novel antibiotic for the treatment of C. difficile infection. METHODS: Ribotyping and susceptibilities were determined for C. difficile isolates from a multicentre, double-blind, Phase 2 study of oral cadazolid in patients with C. difficile infection (NCT01222702, ClinicalTrials.gov; EudraCT 2010-020941-29, European Clinical Trials Database). Patients were randomized to receive 250, 500 or 1000 mg of cadazolid twice daily or 125 mg of vancomycin four times daily, for 10 days. MICs of cadazolid, vancomycin, fidaxomicin, linezolid and moxifloxacin were determined at baseline for all patients and post-baseline for patients with clinical failure or recurrence, using the agar dilution method. RESULTS: Seventy-eight of 84 patients had an evaluable toxigenic C. difficile isolate at baseline. The most frequent PCR ribotype was 027 (15.4%). Cadazolid MICs for baseline isolates (including epidemic strain 027) ranged from 0.06 to 0.25 mg/L. Baseline cadazolid MICs were similar to those of fidaxomicin and lower than those of vancomycin, linezolid and moxifloxacin. For each clinical outcome group (clinical cure, clinical failure, sustained clinical response and clinical failure or recurrence), the baseline cadazolid MIC range was 0.06-0.25 mg/L. Mean (min-max) cadazolid faecal concentration (µg/g) on day 5 was 884 (101-2710), 1706 (204-4230) and 3226 (1481-12 600) for the doses 250, 500 and 1000 mg, respectively. CONCLUSIONS: For all cadazolid doses, the faecal concentration was in excess of several thousand-fold the MIC90 for C. difficile. The MIC of cadazolid for all C. difficile isolates, including epidemic strains, was low and in the same narrow range regardless of treatment outcome.

Retraction speed and chronic poststernotomy pain: A randomized controlled trial.

OBJECTIVES: Approximately 30% of patients develop chronic poststernotomy pain (CPSP) following cardiac surgery with sternal retraction. Risk factors have been described but no causal determinants identified. Investigators hypothesized that opening the sternum slowly would impart less force (and thereby less nerve/tissue damage) and translate to a reduced incidence of CPSP. The main objectives were to determine whether or not slower sternal retraction would reduce the incidence of CPSP and improve health-related quality of life. METHODS: Patients undergoing coronary artery bypass graft surgery were recruited to this randomized controlled trial. Patients were randomized to slow or standard retraction (ie, sternum opened over 15 minutes vs 30 seconds, respectively). Although the anesthesiologist and surgeon were aware of the randomization, the patients, assessors, and postoperative nursing staff remained blinded. Sternotomy pain and analgesics were measured in hospital. At 3, 6, and 12 months postoperatively, all patients completed the Medical Outcomes Survey Short Form and reported on CPSP and complications requiring rehospitalization. Thirty-day rehospitalizations and mortality were recorded. RESULTS: In total, 326 patients consented to participate and 313 were randomized to slow (n = 159) versus standard retraction (n = 154). No clinically relevant differences were detected in acute pain, analgesic consumption, or the incidence of CPSP or health-related quality of life. Although the slow group had significantly more hospitalizations at 3 and 12 months postoperatively, the reasons were unrelated to retraction speed. No differences were observed in 30-day rehospitalizations or mortality. CONCLUSIONS: All outcomes were consistent with previous reports, but no clinically significant differences were observed with retraction speed.

Clinical outcomes, safety, and pharmacokinetics of OPT-80 in a phase 2 trial with patients with Clostridium difficile infection.

OPT-80, a novel, minimally absorbed macrocycle, is a candidate treatment option for Clostridium difficile infection (CDI) based on cure without recurrence of CDI in the hamster challenge model, good in vitro activity against C. difficile, and relative sparing of commensal gram-negative anaerobes. In this open-label, dose-ranging clinical trial, 48 evaluable subjects were randomized to receive either 50, 100, or 200 mg of OPT-80 orally every 12 h for 10 days as treatment for mild to moderately severe CDI. OPT-80 was well tolerated by all subjects. Plasma concentrations were below the lower limit of quantitation in almost one-half of patients and typically

Retrograde Extrusion of Coronary Thrombus During Urgent Aortocoronary Bypass Surgery: A Case Report.

A 73-year-old man underwent urgent coronary artery bypass grafting after an acute myocardial infarction. An angiogram had revealed multivessel disease with a circumflex artery lesion suspected as the primary culprit. On separation from cardiopulmonary bypass, transesophageal echocardiography revealed a new mobile mass in the aortic root. Cardiopulmonary bypass was reinstituted and a large thrombus emanating from the left coronary ostium was surgically removed. We hypothesize that the thrombus had originated from coronary retrograde extrusion during venous grafting. This case illustrates an unusual source of emboli during coronary artery bypass grafting and emphasizes the importance of perioperative transesophageal echocardiography for the prevention of potentially catastrophic outcomes.

Microgravity validation of a novel system for RNA isolation and multiplex quantitative real time PCR analysis of gene expression on the International Space Station.

The International Space Station (ISS) National Laboratory is dedicated to studying the effects of space on life and physical systems, and to developing new science and technologies for space exploration. A key aspect of achieving these goals is to operate the ISS National Lab more like an Earth-based laboratory, conducting complex end-to-end experimentation, not limited to simple microgravity exposure. Towards that end NASA developed a novel suite of molecular biology laboratory tools, reagents, and methods, named WetLab-2, uniquely designed to operate in microgravity, and to process biological samples for real-time gene expression analysis on-orbit. This includes a novel fluidic RNA Sample Preparation Module and fluid transfer devices, all-in-one lyophilized PCR assays, centrifuge, and a real-time PCR thermal cycler. Here we describe the results from the WetLab-2 validation experiments conducted in microgravity during ISS increment 47/SPX-8. Specifically, quantitative PCR was performed on a concentration series of DNA calibration standards, and Reverse Transcriptase-quantitative PCR was conducted on RNA extracted and purified on-orbit from frozen Escherichia coli and mouse liver tissue. Cycle threshold (Ct) values and PCR efficiencies obtained on-orbit from DNA standards were similar to Earth (1 g) controls. Also, on-orbit multiplex analysis of gene expression from bacterial cells and mammalian tissue RNA samples was successfully conducted in about 3 h, with data transmitted within 2 h of experiment completion. Thermal cycling in microgravity resulted in the trapping of gas bubbles inside septa cap assay tubes, causing small but measurable increases in Ct curve noise and variability. Bubble formation was successfully suppressed in a rapid follow-up on-orbit experiment using standard caps to pressurize PCR tubes and reduce gas release during heating cycles. The WetLab-2 facility now provides a novel operational on-orbit research capability for molecular biology and demonstrates the feasibility of more complex wet bench experiments in the ISS National Lab environment.

Cloud-based Electronic Health Records for Real-time, Region-specific Influenza Surveillance.

Accurate real-time monitoring systems of influenza outbreaks help public health officials make informed decisions that may help save lives. We show that information extracted from cloud-based electronic health records databases, in combination with machine learning techniques and historical epidemiological information, have the potential to accurately and reliably provide near real-time regional estimates of flu outbreaks in the United States.

Bacteriology of hospital-acquired pneumonia.

Hospital-acquired pneumonia was studied prospectively for 3 1/2 years in a 549-bed facility with acute medical-surgical care wards, convalescent wards, and a chronic care unit. Bacteriological studies were limited to transtracheal aspirates, pleural fluid, and blood cultures. The predominant isolates in 159 patients were gram-negative bacilli (47%), anaerobic bacteria (35%), Staphylococcus aureus (31%), and Streptococcus pneumoniae (26%). Nearly half of all specimens yielded a polymicrobial flora with more than one potential pathogen. Distribution of pathogens was similar with analysis of all patients, including patients with a monomicrobial infection and patients with bacteremic pneumonia. The prevalence of cases and distribution of bacteria were similar for patients located on acute medical-surgical wards and those in the nursing home care unit. Nosocomial pneumonia was judged directly responsible for lethal outcome in 19% of patients and a contributing factor to death in another 13%.

A multicenter comparative trial of tobramycin and ticarcillin vs moxalactam and ticarcillin in febrile neutropenic patients.

During a multicenter prospective randomized trial in febrile neutropenic patients (neutrophil count, less than 1,000/cu mm), 103 episodes were treated with tobramycin sulfate plus ticarcillin disodium (TT) while 117 were treated with moxalactam plus ticarcillin disodium (MT). The majority of patients had an underlying diagnosis of leukemia (60%) and most (62.8%) had granulocyte counts of less than 100/cu mm at the start of therapy. The response rates for clinically or microbiologically documented episodes were 38 of 60 (55.1%) for TT and 38 of 64 (59.4%) for MT. The MT regimen appeared to be more effective for gram-positive infections (56% vs 33%) while TT appeared more effective for gram-negative infections (64% vs 40%). Nephrotoxicity attributable to study drugs occurred in only 2.3% of cases (one on each treatment arm). Prolongation of the prothrombin time was observed in only six of 78 (7.7%) in the TT arm as compared with 39 of 103 (38%) in the MT arm. Neither regimen was adequate for the unusually high frequency of gram-positive pathogens seen during this study.

Dietary deficiency of phylloquinone and reduced serum levels in febrile neutropenic cancer patients.

In 34 cancer patients with 40 neutropenic febrile episodes requiring broad-spectrum antimicrobial therapy, detailed dietary assessments revealed that deficient and severely deficient phylloquinone intakes (less than or equal to 70 and less than or equal to 25 micrograms/d) were identified during 88% and 38% of all days recorded, respectively. Serum phylloquinone levels and serial prothrombin times (PT) drawn in a similar group of 32 patients revealed that an elevated PT (greater than or equal to 2 s beyond control) was significantly associated (p less than 0.01) with a serum phylloquinone level of less than 4.4 nmol/L. Patients on antimicrobial regimens that suppressed menaquinone-producing intestinal microflora and that contained an N-methylthiotetrazole (NMTT) moiety had an elevated PT significantly more often than did patients receiving antimicrobial agents that preserved the microflora and contained no NMTT moiety (3 of 10 vs 10 of 11, respectively; p = 0.02 Fisher's exact). These data suggest that these patients have a profound deficiency of oral vitamin K intake that may be further augmented by antimicrobial therapy.

Comparison of norfloxacin with cotrimoxazole for infection prophylaxis in acute leukemia. The trade-off for reduced gram-negative sepsis.

A total of 63 neutropenic patients receiving cytotoxic therapy for acute leukemia were randomly allocated to receive norfloxacin (400 mg every 12 hours) or cotrimoxazole (160/800 mg every 12 hours) to prevent bacterial infection. Compliance was more than 95 percent and no adverse effects attributable to the study drugs were observed. The overall incidence of febrile illness (67 percent) was similar between the groups; however, no gram-negative bacillary infections were observed in 31 norfloxacin recipients compared with four of 32 cotrimoxazole recipients. Furthermore, nine norfloxacin recipients had 17 gram-positive bacteremias compared with two in two cotrimoxazole recipients (p = 0.0034). Norfloxacin was more effective than cotrimoxazole for preventing acquisition of aerobic gram-negative bacilli in surveillance cultures. Neither study drug allocation nor the presence of an indwelling central venous catheter influenced outcome among the 42 patients who subsequently received empiric systemic antibiotics for suspected infection. Although gram-positive infection remains an unsolved problem, norfloxacin appears to be a safe, effective, well-tolerated alternative to cotrimoxazole for preventing gram-negative infection in neutropenic patients with acute leukemia.

Randomized controlled trial comparing trimethoprim/sulfamethoxazole and trimethoprim for infection prophylaxis in hospitalized granulocytopenic patients.

The clinical and microbiologic efficacy of trimethoprim alone and trimethoprim/sulfamethoxazole for infection prevention was evaluated in 75 patients during 92 episodes of granulocytopenia. Ultimately, 60 patients were evaluable during 77 episodes of granulocytopenia, 36 episodes in the trimethoprim group and 41 episodes in the trimethoprim/sulfamethoxazole group. The incidence of infection was higher in the trimethoprim group (50 percent) than in the trimethoprim/sulfamethoxazole group (39 percent), but this did not reach statistical significance. Trimethoprim did not appear to be as protective as trimethoprim/sulfamethoxazole when the granulocyte count was less than 100/mm3. In patients receiving trimethoprim/sulfamethoxazole, aerobic gram-negative bacilli cleared from fecal surveillance cultures more often and new aerobic gram-negative bacilli were acquired less often than in those receiving trimethoprim alone (p less than 0.05). More myelosuppression was observed among patients receiving trimethoprim/sulfamethoxazole (p less than 0.001). These observations suggest that trimethoprim alone may not be optimal for preventing colonization and infection in granulocytopenic patients and that combination with other agents may be necessary to increase the spectrum of activity. Trimethoprim/sulfamethoxazole itself may predispose toward an increased risk of infection by prolonging myelosuppression.

Comparison of higher-dose intradermal hepatitis B vaccination to standard intramuscular vaccination of healthcare workers.

OBJECTIVE: To compare the immunogenicity of hepatitis B vaccine administered via intradermal (ID) versus intramuscular (IM) route. METHODS: Subjects chose either to specify the route of immunization or to undergo random allocation to vaccination by the ID (0.15 mL) or the IM (1.0 mL) route. Yeast-derived recombinant hepatitis B vaccine was given at 0, 30, and 180 days. Hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) were measured by microparticle enzyme immunoassay. RESULTS: 763 subjects were enrolled. Baseline screening identified 65 subjects (8%) who were positive for HBsAb or HBcAb. Vaccination was completed by 590 (85%) of 698 enrollees (370 ID, 220 IM). Seroconversion rates (geometric mean titers [GMT]>0 IU/mL HBsAb) for those vaccinated ID were 99% and 96% for screening at 9 months and 1 year post-vaccination, respectively; subjects vaccinated intramuscularly had similar rates of 95% and 96%. Seropositivity rates (GMT > or = 10 IU/mL HBsAb) showed a similar pattern, with 95%, 92%, and 73% at 9 months and 1 and 2 years, respectively, for those vaccinated ID, and 94%, 93%, and 81% for those having IM vaccination. GMT for HBsAb was significantly higher for individuals vaccinated IM than for those vaccinated ID (P<.0001). The GMT ratio for the IM and ID routes decreased over time, being 9.3 at 9 months, 7.8 at 1 year, and 5.9 at 2 years. An unanticipated side effect of intradermal vaccination was skin discoloration at injection sites, which persisted for at least 2 years postvaccination. Two thirds (112/166) of respondents reported that they would have selected the ID route despite the discoloration. CONCLUSIONS: Higher-dose ID vaccination (3 vs 1 microg per injection) uses one sixth of the dose required for standard IM vaccination. It is a cost-effective way to vaccinate populations against hepatitis B virus, but the long-term efficacy of the ID route must still be investigated.

Methicillin-resistant Staphylococcus aureus in tertiary care institutions on the Canadian prairies 1990-1992.

OBJECTIVE: To review experience with methicillin-resistant Staphylococcus aureus (MRSA) in tertiary acute-care teaching hospitals on the Canadian prairies. DESIGN: Retrospective review for a 36-month period, 1990 through 1992. SETTING: Five tertiary acute-care teaching hospitals in three Canadian prairie provinces. METHODS: MRSA isolates and susceptibility were identified through the clinical microbiology laboratory at each institution. For each patient, data collected included duration of institutional residence prior to isolation, patient ethnic background, age, sex, and antimicrobial susceptibility. Epidemiologic typing of strains used restriction fragment length polymorphism analysis by pulsed-field gel electrophoresis. RESULTS: Two hundred fifty-nine MRSA isolates were identified in 135 patients during the 36 months, with substantial institutional variation in number of isolates. No consistent increase in yearly numbers of isolates was apparent. Patients usually had MRSA identified at admission (62%); only one of five centers had the majority of isolates acquired nosocomially. Patients with MRSA present at admission were more frequently of aboriginal (First Nations) ethnicity (62% compared with 14% of nosocomial; P < 0.001). Pulsed-field gel electrophoresis of 167 isolates from 135 patients revealed 46 different strains with little interprovincial or interinstitutional identity of strains. CONCLUSIONS: MRSA isolated in patients in tertiary care institutions in these three Canadian provinces usually is acquired prior to admission. A disproportionate number of isolates are identified in aboriginal Canadians. Epidemiologic typing was consistent with a polyclonal origin of MRSA in this geographic area.

Prolonged and multipatient use of prefilled disposable oxygen humidifier bottles: safety and cost.

OBJECTIVES: Multipatient use and prolonged use of prefilled disposable oxygen humidifier bottles (Aquapak 301, Respiratory Care, Inc., Arlington Heights, IL) were evaluated by performing microbiologic monitoring and a cost analysis on bottles used for varying numbers of patients and lengths of time. METHODS: Humidifiers were hung for a maximum of one month. Monitoring was conducted in 6 different nursing areas. Quantitative cultures were done for aerobes and Legionella. Reusable humidifier bottles also were monitored. RESULTS: Cultures were obtained from 1,311 disposable and 60 reusable humidifiers. No significant bacterial contamination was detected in the prefilled disposable oxygen humidifier units. Ten percent of the reusable bottles were contaminated by organisms associated with skin flora. CONCLUSIONS: Multipatient use and increased duration of use of disposable humidifiers result in cost savings without increasing patient risk. Restricted multipatient use of prefilled disposable oxygen humidifier bottles for a period of one month is a safe and cost-efficient practice.

Should infection control practitioners do follow-up of staff exposures to patient blood and body fluids?

BACKGROUND: The purpose of this study was to determine the efficiency of a joint infection control/occupational health program for the follow-up of accidental blood or bloody body fluid exposures in health care workers. METHODS: A comprehensive staff follow-up program for all blood exposures with known patient sources was initiated in 1989, consisting of patient follow-up by the Infection Control Department (risk assessment for hepatitis B virus [HBV] and [HIV] infection and obtaining of consent for HIV testing) and staff follow-up by the Occupational Health Department. In 1992 a mailed survey was conducted to examine exposure follow-up policies and responsibilities in large teaching hospitals across Canada. RESULTS: A total of 924 blood exposures with known patient sources were reported between January 1989 and December 1993. HIV and HBV screening was obtained for 67.9% and 87.6% of patients assessed as at low risk and 82.3% and 92.2% of those assessed as at high risk for infection, respectively. Two previously unknown HIV-seropositive patients were identified, one of whom had been classified as at low risk (one of 530 [0.19%] patients at low risk who underwent screening). Primary reasons for screening being missed were patient discharge (46.3%) or communication problems (18.0%). The requirement for informed written consent before HIV screening accounted for the difference in completed HIV and HBV screens. Results of the hospital survey indicated that 40.8% of Canadian hospitals follow up all patients who are involved in blood exposures; however, most hospitals still rely on the physician to obtain consent (87.6%). CONCLUSIONS: Use of ICPs to screen patients involved in staff blood exposures during regular hours may be the most efficient method of follow-up, particularly if supplemented by a backup team of health professionals on nights and weekends. Although screening all patients for HBV/HIV may detect patients with undisclosed high-risk behaviors, institutions must decide whether the practice is cost-effective in areas of low prevalence.

Handwashing practices in an intensive care unit: the effects of an educational program and its relationship to infection rates.

Handwashing is the single most important procedure in the prevention of nosocomial infections and yet it remains the most violated of all infection control procedures. With a sequential intervention study in an intensive care unit we have demonstrated that poor handwashing practices are associated with a high nosocomial infection rate, whereas good handwashing practices are associated with a low nosocomial infection rate. An educational and enforcement program designed to improve handwashing procedures can significantly reduce endemic nosocomial infection rates.

A review. Lessons from an animal model of intra-abdominal sepsis.

Intra-abdominal sepsis that involves multiple aerobic and anaerobic bacteria derived from the colonic flora was studied in Wistar rats to determine the relative roles of various microbial species. The rats challenged with pooled colonic contents showed a biphasic disease. Initially, there was acute peritonitis, Escherichia coli bacteremia, and high mortality. In rats that survived this acute peritonitis stage, intra-abdominal abscesses developed, and anaerobic bacteria were the preponderant organisms. Subsequent experiments showed that antibiotics directed against coliforms prevented mortality, whereas agents active against anaerobes reduced the incidence of abscesses. Challenges with Escherichia coli alone produced bacteremia and death, whereas pure cultures of Bacteroides fragilis caused intra-abdominal abscesses. These observations suggest that both coliforms and anaerobes are important pathogens in intra-abdominal sepsis, although the different types of microbes appear to play distinctive roles in the sequence of pathological events.

Cefoxitin plus tobramycin and clindamycin plus tobramycin. A prospective randomized comparison in the therapy of mixed aerobic/anaerobic infections.

The efficacy of therapy with cefoxitin sodium plus tobramycin sulfate, with the tobramycin therapy discontinued if no cefoxitin-resistant pathogens grew from appropriate cultures, was compared with clindamycin phosphate plus tobramycin therapy in mixed aerobic/anaerobic intra-abdominal and female pelvic infections. Of 96 evaluable patients, 39 (76%) of 51 randomized to cefoxitin and 38 (84%) of 45 randomized to clindamycin were cured and an additional seven (14%) of 51 and three (6.7%) of 45, respectively, were improved. Bacteroides fragilis "group" was isolated from 44 (54%) of 82 patients with appropriate specimens. Duration of aminoglycoside therapy was significantly shorter in patients randomized to cefoxitin and tobramycin (mean, 4.1 +/- 1.8 days vs 7.0 +/- 3.2 days). There was a tendency to greater nephrotoxic reactions in patients randomized to clindamycin and tobramycin. We conclude that cefoxitin plus tobramycin with selective early discontinuation of aminoglycoside therapy is an acceptable regimen for the therapy of mixed aerobic/anaerobic infections.