Manifestations and mechanisms of myocardial lipotoxicity in obesity.

Environmental and socioeconomic changes over the past thirty years have contributed to a dramatic rise in the worldwide prevalence of obesity. Heart disease is amongst the most serious health risks of obesity, with increases in both atherosclerotic coronary heart disease and heart failure among obese individuals. In this review, we focus on primary myocardial alterations in obesity that include hypertrophic remodelling and diastolic dysfunction. Obesity-associated perturbations in myocardial and systemic lipid metabolism are important contributors to cardiovascular complications of obesity. Accumulation of excess lipid in nonadipose cells of the cardiovascular system can cause cell dysfunction and cell death, a process known as lipotoxicity. Lipotoxicity has been modelled in mice using high-fat diet feeding, inbred lines with mutations in leptin receptor signalling, and in genetically engineered mice with enhanced myocardial fatty acid uptake, altered lipid droplet homoeostasis or decreased cardiac fatty acid oxidation. These studies, along with findings in cell culture model systems, indicate that the molecular pathophysiology of lipid overload involves endoplasmic reticulum stress, alterations in autophagy, de novo ceramide synthesis, oxidative stress, inflammation and changes in gene expression. We highlight recent advances that extend our understanding of the impact of obesity and altered lipid metabolism on cardiac function.

Impact of sodium-glucose cotransporter-2 inhibitors on heart failure and mortality in patients with cancer.

OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce heart failure (HF) in at-risk patients and may possess antitumour effects. We examined the effect of SGLT2i on HF and mortality among patients with cancer and diabetes. METHODS: This was a retrospective propensity score-matched cohort study involving adult patients with type 2 diabetes mellitus diagnosed with cancer between January 2010 and December 2021. The primary outcomes were hospitalisation for incident HF and all-cause mortality. The secondary outcomes were serious adverse events associated with SGLT2i. RESULTS: From a total of 8640 patients, 878 SGLT2i recipients were matched to non-recipients. During a median follow-up of 18.8 months, SGLT2i recipients had a threefold lower rate of hospitalisation for incident HF compared with non-SGLT2i recipients (2.92 vs 8.95 per 1000 patient-years, p=0.018). In Cox regression and competing regression models, SGLT2i were associated with a 72% reduction in the risk of hospitalisation for HF (HR 0.28 (95% CI: 0.11 to 0.77), p=0.013; subdistribution HR 0.32 (95% CI: 0.12 to 0.84), p=0.021). The use of SGLT2i was also associated with a higher overall survival (85.3% vs 63.0% at 2 years, p<0.001). The risk of serious adverse events such as hypoglycaemia and sepsis was similar between the two groups. CONCLUSIONS: The use of SGLT2i was associated with a lower rate of incident HF and prolonged overall survival in patients with cancer with diabetes mellitus.

Multicenter evaluation of the Cepheid Xpert methicillin-resistant Staphylococcus aureus (MRSA) test as a rapid screening method for detection of MRSA in nares.

The first U.S. multicenter clinical trial to assess the performance of the Cepheid Xpert MRSA assay (Xpert MRSA) was conducted. The assay is a qualitative test designed for the rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) directly from nares swabs. This novel test combines integrated nucleic acid extraction and automated real-time PCR for the detection of a MRSA-specific signature sequence. A total of 1,077 nares specimens were collected from seven geographically distinct health care sites across the United States with prevalence rates ranging from 5.2% to 44%. Nares specimens were tested by (i) the Xpert MRSA assay, (ii) direct culture on CHROMagar MRSA medium (direct CM culture), and (iii) broth-enriched culture (Trypticase soy broth with 6.5% sodium chloride) followed by plating onto CHROMagar MRSA medium (broth-enriched CM culture). When direct CM culture was designated the reference method, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Xpert MRSA assay were 94.3%, 93.2%, 73.0%, and 98.8%, respectively. When broth-enriched CM culture was used as the reference method, the clinical sensitivity, specificity, PPV, and NPV of the Xpert MRSA assay were 86.3%, 94.9%, 80.5%, and 96.6%, respectively. The BD GeneOhm MRSA (BDGO) assay was performed as a comparative molecular method. No statistical performance differences were observed between the Xpert MRSA and BDGO assays when they were compared to culture methods. From this large-scale, multicenter clinical comparison, we conclude that the Xpert MRSA assay is a simple, rapid, and accurate method for performing active surveillance for MRSA in a variety of health care populations.

Antibiotic policy and prescribing strategies for therapy of extended-spectrum beta-lactamase-producing Enterobacteriaceae: the role of piperacillin-tazobactam.

Therapy of infections caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria with an antimicrobial to which they are resistant results in treatment failure, higher cost and increased mortality. The CLSI recommends reporting ESBL-producing strains of Escherichia coli, Klebsiella spp. and Proteus spp. as resistant to all penicillin, true cephalosporin and monobactam antimicrobials, but as susceptible to beta-lactam-beta-lactamase inhibitor combinations, including piperacillin-tazobactam, when they test as such. Current literature supports the action of piperacillin-tazobactam against susceptible strains of ESBL-producing bacteria based on the structure-activity relationship between inhibitors and the ESBLs, as well as on recent clinical outcome studies.

Squeezing the antibiotic balloon: the impact of antimicrobial classes on emerging resistance.

The ongoing problem of emerging antimicrobial resistance has been likened to a balloon where settling one specific issue results in a 'bulge' of even worse problems. However, much has been learned about how to best use our critical antibacterial agents in ways to avoid or even repair some of the resistance damage that has been done. A compilation of current literature strongly suggests that to slow the development of resistance to antimicrobial agents it is optimal to use drugs with more than one mechanism of action or target, to prescribe those with demonstrated ability to minimise or reverse resistance problems, and to avoid underdosing of potent antibiotics. The most recent information also indicates that it is best to limit empirical use of beta-lactam plus fluoroquinolone combination therapy, since these two classes activate some common resistance responses, and using them together can facilitate multidrug resistance in important pathogens, particularly Pseudomonas aeruginosa and Acinetobacter species. This review discusses the role of each major antimicrobial class on resistance development and presents specific strategies for combating the growing problem of multidrug-resistant bacteria. We now have the knowledge to better manage our antimicrobial agent prescribing practices, but finding the will and resources to apply our understanding remains a formidable challenge.

Vancomycin-resistant Enterococcus faecium sepsis following persistent colonization.

Vancomycin-resistant enterococci have emerged as important nosocomial pathogens and represent a serious threat to patients with impaired host defenses. We describe a patient with leukemia who developed prolonged colonization with vancomycin-resistant Enterococcus faecium and ultimately died of sepsis due to this multidrug-resistant organism. This case report confirms that colonization with vancomycin-resistant enterococci may last indefinitely and that asymptomatic carriage can lead to invasive infection.

Enterococcus faecium bacteremia: does vancomycin resistance make a difference?

BACKGROUND: Enterococcus faecium has received increased attention, primarily due to the emergence of vancomycin resistance. The purpose of this investigation was to study the epidemiological characteristics of vancomycin-resistant E faecium (VRE) bacteremia and to determine the clinical impact of vancomycin resistance on the outcome of patients with this infection. METHODS: We retrospectively analyzed the clinical features and outcome of 53 patients with E faecium bacteremia. RESULTS: From January 1992 until December 1995, there were 32 episodes of bacteremia caused by vancomycin-susceptible E faecium (VSE) and 21 caused by VRE. An intra-abdominal site was the most common source of bacteremia in both groups. All of the VRE and 78% of VSE bacteremia cases were nosocomially acquired. Previous administration of vancomycin was associated with VRE bacteremia (P<.001), as were indwelling bladder catheters (P=.01). Fifty-nine percent of the patients with VSE bacteremia survived vs 24% with VRE (P=.009), despite similar severity-of-illness scores. In 62% of the patients with VRE sepsis, death was related to the bacteremia (P=.01). Patients infected with VRE had longer hospitalizations than those with VSE (34.8 vs 16.7 days, respectively) (P=.004), were more likely to be on the medical service (P=.03), and on the average, had hospitalization costs of more than $27,000 per episode than did patients with VSE bloodstream infection ($83,897 vs $56,707, respectively) (P=.04). CONCLUSIONS: Vancomycin-resistant E faecium bacteremia is a complication of prolonged hospitalization in debilitated patients. Vancomycin resistance has a negative impact on survival in patients with E faecium bacteremia and leads to higher health care costs.

Fungal meningitis manifesting as hydrocephalus.

Four patients with fungal meningitis and hydrocephalus were treated by placement of intraventricular shunts prior to the diagnosis of infection. As a consequence, they were subjected to the risks of surgery as well as to shunt suprainfection. We suggest that chronic meningitis be ruled out in all patients prior to placement of shunts. Preoperative evaluation should include the examination of cisternal or ventricular CSF when a lumbar CSF specimen is nondiagnositc. When fungal meningitis is present, a course of amphotericin B should be initiated and the CSF sterilized prior to the placement of the permanent extracranial shunt. Where acute hydrocephalus supervenes, temporary ventricular drainage may be employed. In some cases of fungal meningitis, the symptoms of hydrocephalus will be resolved with antifungal therapy alone, obviating the need for ventricular decompression.

Reduction of unnecessary intravenous catheter use. Internal medicine house staff participate in a successful quality improvement project.

BACKGROUND: We had previously observed that a large proportion of peripheral intravenous (i.v.) catheters placed in patients on a regular medical ward at our hospital were unnecessary. We conducted the current study to assess the effect of a quality improvement project led by medicine house staff on the prevalence of unnecessary peripheral i.v. catheters (those without any therapeutic use, referred to as idle). METHODS: All patients on four regular-care medical wards of a large university-affiliated veterans hospital were included in the study. The proportion of i.v. catheter episodes in which catheters were idle 2 or more consecutive days (idle episodes) and the proportion of patients exposed to an idle catheter episode were determined by direct observation, chart review, and patient interview before and after a multidisciplinary quality improvement task force defined guidelines for appropriate i.v. catheter use and made recommendations for hospital policy changes related to i.v. catheter use. RESULTS: The proportion of all i.v. catheter episodes that were idle catheter episodes decreased significantly after the intervention (42% before vs 29% after, P < .01), as did the proportion of patients with an i.v. catheter who had at least one idle i.v. catheter episode (43% vs 27%, P < .001). CONCLUSIONS: This quality improvement effort successfully reduced unnecessary i.v. catheter use. We suspect that house-staff involvement in the intervention was critical. We encourage other academic medical centers to involve house staff in quality improvement activities to improve patient care and to enhance the education of house staff regarding quality improvement processes.

Serious staphylococcal infections with strains tolerant to bactericidal antibiotics.

The clinical response in 20 cases of serious staphylococcal infection was compared with the in vitro resistance or "tolerance" of the infecting Staphylococcus to killing by antibiotics used in treatment. Cases were divided into two groups: (1) patients who initially received nonbactericidal antibiotics (ten cases), and (2) patients who initially received bactericidal antibiotics with or without nonbactericidal antibiotics. Mortality due to uncontrolled staphylococcal infection was 40% (4/10) in group 1 as compared with no mortality (1/10) in group0) in group 1 as compared with no mortality (0/10) in group 2. The duration of positive cultures after start of therapy in group 1 (mean, 6.1 days) was significantly longer than that in group 2 (mean, 1.3 days). The duration of fever after start of therapy in group 1 was not significantly different when compared with group 2.

Clostridium difficile-associated diarrhea and colitis in adults. A prospective case-controlled epidemiologic study.

In a one-year period, 149 adult cases of Clostridium difficile-associated diarrhea and colitis were compared with 148 diarrhea-free controls. Eighty-seven percent were nosocomial and 75% were on surgical services. Endoscopy revealed pseudomembranes in 51% of the 109 cases in which stool cytotoxin was present, compared with 11% of the 40 cases that were culture-positive but cytotoxin-negative. Cases diagnosed only by stool culture showed essentially no differences from controls, 21% of whom had asymptomatic stool colonization. We estimate that only 20% of these cases had diarrhea due to C difficile. Compared with controls, cases diagnosed by the presence of cytotoxin or pseudomembranes were found to have been hospitalized longer at diarrhea onset, to have had more antecedent infections, and to have received clindamycin, multiple antimicrobials, and therapeutic antimicrobials more often than controls, but controls received prophylactic antimicrobials more frequently than cases. Cultures of the environment, patients, and personnel failed to detect a mechanism of acquisition.

Emergence of ciprofloxacin resistance in nosocomial methicillin-resistant Staphylococcus aureus isolates. Resistance during ciprofloxacin plus rifampin therapy for methicillin-resistant S aureus colonization.

We initiated a randomized, single-blinded trial of ciprofloxacin plus rifampin vs sulfamethoxazole and trimethoprim plus rifampin in the therapy for patients who underwent colonization with methicillin-resistant Staphylococcus aureus (MRSA). Patients who were colonized with MRSA received 2 weeks of either regimen. The study was terminated after the enrollment of 21 subjects due to the recognition of ciprofloxacin resistance in 10 of 21 new MRSA isolates during the last 2 months of the study. Five of the 10 patients with ciprofloxacin-resistant MRSA isolates had never received ciprofloxacin. Long-term (6-month) eradication had been achieved in only three of 11 ciprofloxacin plus rifampin and four of 10 sulfamethoxazole and trimethoprim plus rifampin recipients. The use of this new fluoroquinolone for the eradication of MRSA colonization is usually not effective and may risk the development of ciprofloxacin resistance in MRSA within the hospital environment.

The incidence of antimicrobial allergies in hospitalized patients: implications regarding prescribing patterns and emerging bacterial resistance.

BACKGROUND: The development of antimicrobial guidelines is one way in which institutions attempt to control emerging resistance, but the real challenge falls on promoting and ensuring adherence to these guidelines. Investigating reasons for the prescribing of alternative antimicrobial agents outside of these guidelines is crucial for modifying practices that may adversely impact institutional antimicrobial goals. METHODS: Retrospective cross-referencing of computerized pharmacy printouts and concurrent manual medical record review. RESULTS: Approximately 25% (470/1893) of the patients requiring antimicrobial therapy reported an allergy to at least 1 antimicrobial agent. The most commonly reported antimicrobial allergy was penicillin (295/1893 [15.6%]). Eighty-five patients (18.1%) reported having an allergy to 2 or more antimicrobial agents. Only 4% (27/601) of the reported antimicrobial allergies contained documentation as to the nature of the specific allergic reactions, while a manual medical record review revealed that 32% (23/73) of the antimicrobial allergies contained documentation of the specific allergic reaction. Ninety-eight (39. 7%) of 247 patients reporting an allergy only to penicillin and/or cephalosporin received vancomycin in comparison with 247 (17.4%) of 1423 patients without any antimicrobial allergies (P<.001). Similarly, 53 (21.5%) of 247 patients with reported penicillin and/or cephalosporin allergies received levofloxacin compared with 114 (8.0%) of 1423 patients without any antimicrobial allergy (P<. 001). CONCLUSION: The incidence of penicillin allergy at our institution exceeds population averages. This finding, in combination with limited documentation of drug allergies, appears to lead to the prescribing of alternative antimicrobial agents that do not fit into institutional antimicrobial guidelines and, in some instances, may put the patient at risk for infection and/or colonization with resistant organisms. Use of these alternative agents may adversely impact the ability to manage emerging antimicrobial resistance.

Selective bacterial adherance to cardiac endothelial cells in tissue culture.

The adherence of 16 gram-positive bacterial isolates and eight gram-negative bacterial isolates to cardiac endothelial cells from rabbits, chickens, pigs and opossums was evaluated using a tissue culture system. A single coagulase-negative staphylococcus was significantly more adherent over cell cultures and controls than any other organism tested. Adherent bacteria were sticky to most surfaces tested. No differences in adherence were demonstrated between gram-positive and gram-negative bacteria when they were compared as groups.

Detection of vancomycin-resistant enterococci before and after antimicrobial therapy: use of conventional culture and polymerase chain reaction.

Antimicrobial therapy can increase the colonization density of gastrointestinal vancomycin-resistant enterococci (VRE). Among previously VRE-colonized patients, we evaluated VRE colonization before and after initiation of antimicrobial therapy by means of polymerase chain reaction (PCR) and culture. Perianal swab samples were obtained at admission to the hospital and after receipt of antimicrobial therapy. At admission, 12 (21%) of 56 patients were culture positive, and 17 (30%) had vanA or vanB genes detected by PCR. Culture results showed that 25 (86%) of 29 culture-negative patients from whom a second swab sample was obtained remained culture negative, 2 (6.9%) had a relapse of colonization with a strain related to the previously colonizing strain type (2 and 6 days after admission), and 2 (6.9%) tested positive for a previously undetected strain type (16 and 19 days after admission). PCR at admission detected VRE in 1 of the 2 patients who later relapsed. Patients with negative results of culture of the initial swab sample and of PCR were unlikely to relapse after receipt of antimicrobial therapy.

Race/ethnicity as a risk factor for HIV-1 infection among Connecticut intravenous drug users.

This cross-sectional study of 341 entrants to drug abuse treatment in four Connecticut cities in 1986-1987 evaluated whether demographic, behavioral, viral serologic, or economic differences explained the disproportionate risk of human immunodeficiency virus type 1 (HIV-1) infection among black and Hispanic intravenous drug users (IVDUs), relative to non-Hispanic white IVDUs. Blacks [odds ratio (OR) = 9.0, 95% confidence interval (CI) = 5.1-15.9] and Hispanics (OR = 4.1, 95% CI = 1.9-8.8) were at increased risk of HIV-1 infection, relative to non-Hispanic whites. Those who lived closer to New York City, injected drugs more frequently, used intravenous drugs for a longer duration, used shooting galleries, had greater numbers of sexual partners, had human cytomegalovirus (CMV) or hepatitis B virus (HBV) antibodies, and had the lowest annual incomes were also at increased risk. However, none of these other factors accounted for the black and Hispanic HIV-1 risk in stratified analysis. Black race, Hispanic ethnicity, proximity to New York City, and number of drug injections in the past year each also remained significant, independent risk factors in a multivariate analysis. The increased HIV-1 risk of nonwhite IVDUs remained unexplained. Behavioral, sociologic, and/or biologic factors not identified in this study may modulate HIV-1 transmission dynamics in IVDUs.

Ehrlichiosis presenting as a life-threatening illness with features of the toxic shock syndrome.

OBJECTIVE: To describe clinical and laboratory features of patients with severe ehrlichiosis, some of whom presented with toxic shock syndrome (TSS)-like illnesses, and to report, to our knowledge, the first documented fatal case of ehrlichiosis in a child. DESIGN: Case series. SETTING: Tertiary-care medical center. PATIENTS: All patients with documented ehrlichiosis during a 3-year period, August 1, 1989, to July 31, 1992. RESULTS: Eight patients (age range: 2 to 46 years) met clinical and serologic diagnostic criteria for ehrlichiosis. The mean interval from first contact with a physician to initiation of appropriate antibiotic therapy was 4.6 days (range: 1 to 11 days). All eight patients with ehrlichiosis had fever, chills, thrombocytopenia, and abnormal liver function test results. Most patients also had rash (seven), conjunctival hemorrhage or erythema (six), and leukopenia (six). Four cases met diagnostic criteria for TSS with fever, hypotension, rash, and multiorgan dysfunction. Two patients required mechanical ventilation, and one of these, a 6 1/2-year-old boy, died of complications of the infection. A ninth patient with probable ehrlichiosis also met diagnostic criteria for TSS. CONCLUSIONS: Human ehrlichiosis can present as a severe, life-threatening illness that may resemble TSS. The diagnosis of ehrlichiosis was not considered by the physicians who first cared for these patients. Greater awareness of the potential severity of ehrlichiosis is needed to ensure that proper treatment is initiated early in the course of the disease.

Treatment of ciprofloxacin- and ceftizoxime-induced resistant gram-negative bacilli.

Gram-negative bacilli that had been selected for resistance to either ciprofloxacin or ceftizoxime as a result of previous exposure to these agents were inoculated into semipermeable subcutaneous chambers in rabbits, modeling a locally neutropenic closed-space infection. Five resistant organisms, one Serratia marcescens (157) and four Pseudomonas aeruginosa (864, 876, 913, and 915) strains, were selected by previous therapy with ciprofloxacin, and six Pseudomonas strains (833, 845, 864, 876, 913, and 915) were selected by previous therapy with ceftizoxime. Animals were treated with either single antibiotics or combinations of antibiotics for four days, and the response was determined by quantitative bacterial count measurements. The selected (induced) resistance was stable for at least four days, both in vivo and in vitro, but was limited to the antibiotic class of the agent used for induction. Four of five isolates for which resistance had been induced by ciprofloxacin returned to preinduction susceptibility by the eight day of subculture. Organisms that were selected for resistance to ciprofloxacin were successfully treated by a combination of azlocillin and amikacin, and were as sensitive to that regimen as were the parent, uninduced strains. Organisms selected for resistance by pretreatment with ceftizoxime were successfully treated by the combination of ciprofloxacin plus azlocillin, and this regimen was also equally active against the selected strains as it was against the parental isolates. Although selection or induction of resistance is a potential problem with all new potent antimicrobial agents, it appears that infections due to these isolates can still be treated successfully through the use of appropriate combination chemotherapy.

Evaluation of ciprofloxacin's synergism with other agents by multiple in vitro methods.

The efficacies of ciprofloxacin, ceftizoxime, azlocillin, mezlocillin, and amikacin (minimal inhibitory concentration and minimal bactericidal concentration) against six Pseudomonas aeruginosa, six Enterobacteriaceae, and six group D streptococcal strains were evaluated using both agar and broth susceptibility methods, two inoculum sizes (5.7 log10 colony-forming units (cfu)/ml and 7.7 log10 cfu/ml), and aerobic and anaerobic incubation conditions. The results showed agreement between broth and agar methods of susceptibility determination; inoculum effects with beta-lactam antimicrobials; and decreased susceptibility to amikacin under anaerobiasis. Ciprofloxacin combined with azlocillin, ceftizoxime, or aminoglycosides in broth microdilution checkerboards against 100 gram-negative bacilli and gram-positive cocci demonstrated that ciprofloxacin combined with azlocillin or ceftizoxime was synergistic against at least 50 percent of P. aeruginosa and Serratia marcescens isolates and that ciprofloxacin combined with amikacin was synergistic against at least 50 percent of S. marcescens and Staphylococcus aureus isolates. Ciprofloxacin and azlocillin in combination were evaluated by microdilution checkerboard, agar dilution, and broth macrodilution time-kill methods at two inoculum sizes to assess antibacterial activity. Comparison between in vitro combination methods showed the following: the presence or absence of checkerboard synergism (as defined by the fractional inhibitory concentration index and the fractional bactericidal concentration index) with ciprofloxacin and azlocillin did not correlate with time-kill results; and good agreement between methods when comparing broth macrodilution time-kill (3 log10 cfu/ml or more decrease) with antimicrobial combinations at a single concentration in both agar and microdilution broth for ciprofloxacin and azlocillin. Rabbit studies using subcutaneous dialysis membrane chambers inoculated with six P. aeruginosa, six Enterobacteriaceae, and six group D streptococcal strains were performed using ciprofloxacin, azlocillin, ceftizoxime, and amikacin alone and in combination as therapy. In vitro testing of antibiotic combinations that provided the best prediction of in vivo outcome were combination antibacterial activity (3 log10 cfu/ml or more decrease) at 24 hours using either broth macrodilution time-kill or antimicrobial combinations at a single concentration in either agar or broth (microdilution). For the most efficacious in vivo combination, ciprofloxacin plus azlocillin, there was in vitro correlation with in vivo outcome for 17 of 18 isolates.

Therapy of lower extremity infections with ciprofloxacin in patients with diabetes mellitus, peripheral vascular disease, or both.

PURPOSE: Lower extremity infections in the presence vascular insufficiency are difficult and costly to treat. Few well-controlled clinical trials evaluating the management of these infections exist. We decided to investigate the ability of a new fluoroquinolone, ciprofloxacin, to reduce the morbidity associated with these infections and the amount of in-hospital time required for the administration of antibiotic therapy. PATIENTS AND METHODS: Forty-eight patients with peripheral vascular disease (46 with diabetes mellitus) who presented to the hospital for treatment of lower extremity infections were randomized in a blinded fashion to receive oral ciprofloxacin at a dosage of either 750 mg or 1,000 mg twice daily. Patients with osteomyelitis received three months of therapy and those with infections limited to soft tissues, three weeks of ciprofloxacin treatment. All subjects were followed for one year. RESULTS: One patient received an amputation 24 hours after enrollment, and two patients discontinued therapy after 20 and 34 days because of adverse effects and were not evaluable. At the one-year follow-up, 27 of the 45 (60 percent) evaluable patients had a fully successful outcome defined as not requiring either repeat antimicrobial therapy for their initial infection or amputation of the involved extremity. In the group of 18 patients in whom therapy failed, a total of only nine amputations were required. In the 15 patients whose lesion closed during therapy, 93% (14 patients) experienced a long-term successful outcome. CONCLUSION: Treatment with this new fluoroquinolone offers promise for the improved outcome of patients with the serious infectious complication of infected lower extremity ulcerations in peripheral vascular disease, diabetes mellitus, or both.