Postantibiotic effects and bactericidal activities of clarithromycin-14-hydroxy-clarithromycin, versus those of amoxicillin-clavulanate, against anaerobes.

The bactericidal activities and postantibiotic effects (PAE) of clarithromycin-14-hydroxy-clarithromycin and amoxicillin-clavulanate against Bacteroides fragilis and Peptostreptococcus anaerobius were determined. A concentration of twice the MIC resulted in bactericidal activity against four of four and three of four organisms at 24 h with clarithromycin-14-hydroxy-clarithromycin and amoxicillin-clavulanate, respectively. The PAE of clarithromycin-14-hydroxy-clarithromycin was 1.44 to 3.20 h, compared to the less than 1 h of amoxicillin-clavulanate. Clarithromycin-14-hydroxy-clarithromycin possesses good activity against susceptible anaerobes.

Modified time-kill assay against multidrug-resistant Enterococcus faecium with novel antimicrobial combinations.

This study used a modified time-kill assay to compare the in-vitro activity of chloramphenicol and quinopristin/dalfopristin combined with vancomycin, ampicillin or gentamicin against multidrug-resistant Enterococcus faecium. The assay uses standardized time-kill methods with the following modifications: centrifugation of the test tubes at 1-2 h intervals, removal of supernatant and resuspension of bacteria in media containing antibiotic concentrations corresponding to simulated steady-state serum concentrations. None of the agents, alone or in combination, produced bactericidal or synergic activity. The modified time-kill assay more closely simulates in-vivo conditions and may provide a better qualitative assay to determine the interaction between antimicrobial agents and bacteria.

In vitro activity of RPR 106972 alone and in combination with vancomycin, ampicillin, and gentamicin against multidrug-resistant enterococci.

This investigation used checkerboard and time-kill assays to evaluate the in vitro activity of RPR 106972 (45% pristinamycin IB and 55% pristinamycin IIB) alone and in combination with vancomycin or ampicillin +/- gentamicin against multidrug-resistant enterococci. The checkerboard procedure resulted in synergistic or additive effects in 91% of the isolates with the combination of RPR 106972 plus vancomycin versus 68% with RPR 106972 plus ampicillin. The addition of gentamicin to either combination resulted in synergistic or additive results in 100% of the isolates. Inhibitory activity was observed with the time-kill assay with mean change in log10 CFU/mL at 24 h of -0.31 for RPR 106972, 3.3 for vancomycin, -0.46 for RPR 106972 plus vancomycin, and -0.35 for RPR 106972 plus vancomycin and gentamicin. No antagonism was noted with any of the combinations. RPR 106972 demonstrates good inhibitory activity against Enterococcus faecium and may prove useful in the treatment of enterococcal infections.

Levofloxacin and sparfloxacin: new quinolone antibiotics.

OBJECTIVE: To discuss the pharmacology, pharmacokinetics, spectrum of activity, clinical trials, and adverse effects of levofloxacin and sparfloxacin, two new fluoroquinolone antibiotics. DATA SOURCES: Literature was identified by a MEDLINE search from January 1985 to September 1997. Abstracts and presentations were identified by review of program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy from 1988 to 1996. STUDY SELECTION: Randomized, controlled clinical studies were selected for evaluation; however, uncontrolled studies were included when data were limited for indications approved by the Food and Drug Administration (FDA). In vitro data were selected from comparison trials whenever available. Only in vitro trials that provided data on the minimum inhibitory concentrations required to inhibit 90% of isolates were used. Data from North American studies were selected whenever available. DATA EXTRACTION: Data were evaluated with respect to in vitro activity, study design, clinical and microbiologic outcomes, and adverse drug reactions. DATA SYNTHESIS: Levofloxacin and sparfloxacin are active against pathogens frequently involved in community-acquired upper and lower respiratory tract infections, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae. Both compounds have enhanced activity compared with ciprofloxacin against most gram-positive bacteria, including enterococci, streptococci, and staphylococci, and retain good activity against most Enterobacteriaceae and Pseudomonas aeruginosa. Sparfloxacin has greater anaerobic activity than levofloxacin, which is more active than ciprofloxacin or ofloxacin. Although many clinical studies are available only in abstract form, the clinical data demonstrate that these new quinolones are effective for most community-acquired upper and lower respiratory tract infections, urinary tract infections, gonococcal and nongonococcal urethritis, and skin and skin structure infections. FDA-approved indications are limited for both compounds to date. CONCLUSIONS: Levofloxacin and sparfloxacin have improved gram-positive activity compared with that of older fluoroquinolones, and are administered once daily. Sparfloxacin-associated photosensitivity may limit its therapeutic usefulness. Clinical trials confirm that these agents are as effective as traditional therapies for the management of community-acquired pneumonia, acute exacerbations of chronic bronchitis, sinusitis, urinary tract infections, acute gonococcal and nongonococcal urethritis, and skin and skin structure infections.

Pharmacoeconomic analysis of ampicillin-sulbactam versus cefoxitin in the treatment of intraabdominal infections.

We conducted a retrospective pharmacoeconomic analysis of a prospective, multicenter, double-blind, randomized, controlled trial comparing the beta-lactamase inhibitor combination ampicillin-sulbactam (96 patients) and the cephalosporin cefoxitin (101) in the treatment of intraabdominal infections. An institutional perspective was adopted for the analysis. The primary outcomes of interest were cure and failure rates, development of new infection, and antibiotic-related adverse events. Epidemiologic data pertaining to outcomes was retrieved primarily from the trial, although results of other published studies were taken into consideration through extensive sensitivity analyses. Data pertaining to potential resource use and economic impact were retrieved mainly from the University Health Consortium and hospital-specific sources. When considering only costs associated with drug acquisition through cost-minimization analysis, a potential savings of $37.24/patient may be realized with ampicillin-sulbactam relative to cefoxitin based on an average 7-day regimen. Outcome data collected for the entire hospitalization during the trial revealed an approximately 9% greater frequency of failure with cefoxitin relative to ampicillin-sulbactam. When considering all outcomes of interest in the initial base-case analysis, a potential cost savings of approximately $890/patient may be realized with ampicillin-sulbactam relative to cefoxitin. In assessing the impact of the significant variability in probability and cost estimates, Monte Carlo analysis revealed a savings of $425/patient for ampicillin-sulbactam over cefoxitin (95% CI -$618 to $1516 [corrected]). Given the model assumptions, our analysis suggests a 78% certainty level that savings will be experienced when ampicillin-sulbactam is chosen over cefoxitin.

In vitro activity of chloramphenicol alone and in combination with vancomycin, ampicillin, or RP 59500 (quinupristin/dalfopristin) against vancomycin-resistant enterococci.

Using a checkerboard assay, ampicillin, vancomycin, and RP 59500, each in combination with chloramphenicol, were tested for synergy against 23 isolates of vancomycin-resistant enterococci. Additive effects were seen in 62.5% of the isolates when exposed to chloramphenicol plus RP 59500. Additive effects were observed in 20% and 15% of isolates with chloramphenicol plus vancomycin or ampicillin, respectively. No antagonism was noted.

Polyhexamethylene biguanide (PHMB) in the treatment of experimental Fusarium keratomycosis.

PURPOSE: We wanted to determine whether topical polyhexamethylene biguanide (PHMB) 0.02% was effective in the treatment of experimental Fusarium keratomycosis in rabbits. METHODS: Fusarium solani keratomycosis was induced in the eyes of 12 New Zealand white rabbits. The rabbits were treated with PHMB 0.02% in one eye and placebo in the other eye for 6 days. The rabbits were evaluated in a masked fashion using a standardized system for clinical progression of the disease. Then the corneas were trephined and growth of F. solani in colony-forming units per milliliter (CFU/ml) determined. RESULTS: Clinical evaluation demonstrated no significant mean difference (p > 0.10) in clinical scores between treated and control eyes on day 6 (0.583 +/- 2.503). There was a significant mean CFU difference (p = 0.06) between treated eyes and control eyes (182.5 +/- 314.44). Seven of 12 eyes (58%) in the PHMB group exhibited no growth, whereas two of 12 (17%) eyes reported no growth in the control group. One of 12 eyes (8%) reported > 100 CFU in the PHMB group, whereas seven of 12 eyes (58%) reported > 100 CFU in the control group. CONCLUSIONS: PHMB 0.02% was effective in significantly reducing the fungal growth in our rabbit model of Fusarium keratomycosis. The future role of PHMB in the treatment of Fusarium keratitis needs to be further evaluated.

Therapeutic modalities for mechanical cleansing of the colon.

Mechanical cleansing of the colon is an accepted standard of practice prior to colon surgery, and endoscopic and radiographic procedures. Cleansing the bowel prior to these procedures increases the accuracy of the diagnostic procedures and decreases the morbidity and mortality following surgery, where fecal contamination is a concern. Mechanical cleansing agents are sometimes used for acute constipation, but because of the extent and harshness of the evacuation they induce, and because of their adverse effects, they are not used for long-term management of constipation. Dosages vary among products, procedures, and individuals. Manufacturer guidelines should be consulted for proper dosing and administration.

Drug-lab interactions: implications for nutrition support. Acetylcysteine interference with urine ketone test.

It is important that health care professionals be aware of the potential for medications to interfere with clinical laboratory tests. Medications can cause in vivo effects when the concentration or activity of the analyte is altered before the analysis and therefore the assay result is true and accurate. An in vitro effect occurs when the medication interferes with the assay, and the result is erroneous and cannot be interpreted. This report describes a recently identified case of interference of acetylcysteine with the urine test for ketones and demonstrates the importance of a thorough medication review in evaluating abnormal laboratory tests.

Update on Clostridium difficile-induced colitis, Part 2.

Clostridium difficile is a nosocomial pathogen able to survive unfavorable environments by sporulation; when conditions advantageous for rapid growth appear, the vegetative form is regenerated. Lack of conscientious hand washing and failure of health care providers to use disposable gloves facilitate transmission within institutions. Exposure to certain antimicrobials expedites C. difficile overgrowth within the colon by altering the composition of the normal gut microflora. Antineoplastic agents may also precipitate CDIC. The characteristics of the colonizing strain, the properties of the inciting drug, and individual host factors collectively seem to govern the expression of the disorder. Clinical presentations range from self-limiting diarrhea to severe diarrhea accompanied by abdominal pain, fever, and leukocytosis to potentially life-threatening PMC. A preponderance of data supports the interpretation that oral metronidazole and oral vancomycin are therapeutically equivalent for the treatment of all but the most severe cases of CDIC. Whether the two drugs are equivalent in severe CDIC is controversial and will probably remain so in the absence of a well-designed trial to expand on the findings of the study by Teasley et al. Because of the cost difference and therapeutic equivalence, oral metronidazole should be the preferred routine treatment for CDIC; oral vancomycin should be reserved for severe cases and cases that fail to respond to at least six days of oral metronidazole therapy. Another important argument, albeit a hypothetical one, for limiting institutional use of oral vancomycin is to minimize selective environmental pressure for the emergence and dissemination of vancomycin-resistant enterococci. An epidemic outbreak of CDIC caused by clindamycin-resistant C. difficile in an institution where clindamycin use was extremely high illustrates the possible consequences of such selective pressure. Oral metronidazole 250 mg four times daily will usually provide a satisfactory response, but clinicians may wish to consider increasing the total daily dose for some patients who have symptoms like fever and leukocytosis. For oral vancomycin, 125 mg four times daily is sufficient in virtually all circumstances. Ten days of therapy is usually adequate for either drug. CDIC in a patient unable to take medications orally presents a bit of a therapeutic dilemma. Two approaches that appear effective are rectal administration of vancomycin and intravenous administration of metronidazole, although intravenous metronidazole can fail to work, possibly because the colonic concentrations achieved are inadequate. Clinicians may wish to consider a total daily dose of intravenous metronidazole that is at the upper end of the adult dosage range, if this is feasible.(ABSTRACT TRUNCATED AT 400 WORDS)

Update on Clostridium difficile-induced colitis, Part 1.

Recent findings on the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of Clostridium difficile-induced colitis (CDIC) are discussed. CDIC is a gastrointestinal disorder that results from colonization by and overgrowth of C. difficile. Among patients in the community who are treated with an oral antimicrobial, only 1 to 3 individuals per 100,000 develop CDIC, compared with as many as 1 per 100 hospitalized patients treated with an antimicrobial. The requirements for CDIC are (1) a readily available source of C. difficile; (2) exposure to drugs, most commonly certain antimicrobials, that disrupt the normal colonic microflora; (3) production of the requisite cytotoxins by the C. difficile strain colonizing the colon; and (4) the presence of individual risk factors, including advanced age, severe underlying illness, and a prolonged hospital stay. Among the varied clinical manifestations of CDIC, diarrhea is predominant and is often the sole symptom. In more severe cases, fever and leukocytosis are also present. The formation of pseudomembranous plaques is pathognomonic but relatively infrequent. Presumptive diagnosis is usually based on a positive cytotoxin assay result in the symptomatic patient. Patients who respond to discontinuation of the inciting drug or drugs should not be treated indiscriminately with antimicrobials. Asymptomatic carriers should not be treated, and a period of watchful waiting may be advisable in mild cases. When treatment is necessary, oral metronidazole is the agent of choice in all but the most severe cases. Whether oral metronidazole is therapeutically equivalent to oral vancomycin in severe CDIC is controversial. Regardless of the antimicrobial used, some patients suffer a recurrence of CDIC and a few have several relapses. There have been no comparative studies of treatment for relapsing CDIC. Of the investigational treatments, the tiacumicin macrolides and the yeast Saccharomyces boulardii appear most promising. Diagnostic assays based on the polymerase chain reaction should allow more timely intervention. Health care professionals who improve their understanding of CDIC will be better able to recognize the disorder, select the best treatment, and perhaps reduce the frequency of CDIC in hospitalized patients by working to alter patterns of antimicrobial use.