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Biomedical subjects

C A Kauffman

Publications and source records attributed to C A Kauffman.

At least 73 records · Page 4Linked to original sources

Comparative in vitro activity of quinupristin/dalfopristin against multidrug resistant Enterococcus faecium.

The in vitro susceptibilities of 82 strains of vancomycin resistant Enterococcus faecium (VREF), (49 vanA and 33 vanB) from over 13 hospitals in Europe and United States were studied. The MIC for several antibiotics showed high levels of resistance to vancomycin, ampicillin, gentamicin, and imipenem. All VREF strains were highly susceptible to quinupristin/dalfopristin with a MIC 90% of 0.5 microgram/ml for both vanA and vanB phenotypes. Time-kill and synergy studies of VREF for quinupristin/dalfopristin alone and quinupristin/dalfopristin in combination with several antibiotics (ampicillin, gentamicin, ciprofloxacin, rifampin and novobiocin) did not show bactericidal activity. In induction experiments using SF6550, (VREF, a vanA strain), quinupristin/dalforpristin showed a delay in the expression of vancomycin resistance by 2.5 hours. The results of this study show quinupristin/dalfopristin to have excellent in vitro activity versus multiple resistant E. faecium.

Anti-Bacterial Agents↗

Susceptibility of ciprofloxacin-resistant staphylococci and enterococci to trovafloxacin.

The susceptibilities of clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and enterococci obtained over a 13-year period were tested for trovafloxacin, a new fluoroquinolone, and ciprofloxacin. For MRSA, MIC50 values for trovafloxacin increased from 0.03 microgram/ml to 1 microgram/ml from 1984-1985 to 1995-1996, but were lower than those noted for ciprofloxacin, which increased from 0.25 microgram/ml to > 8 micrograms/ml during the same period. Trovafloxacin also showed lower MIC50 values (0.12-0.25 microgram/ml) than ciprofloxacin (MIC50 of 0.5-1 microgram/ml) for E. faecalis isolates from 1985 through 1991, but against E. faecium and E. faecalis isolated in 1995-1996, the MIC50 values for both trovafloxacin and ciprofloxacin were 2 micrograms/ml and the MIC90 values were > or 8 micrograms/ml. Thus, cross-resistance between fluoroquinolones was shown for both enterococci and MRSA. Whether the greater intrinsic activity of trovafloxacin might allow its use in treating MRSA and enterococcal infections remains to be seen.

Anti-Infective Agents↗

Treatment of lymphocutaneous and visceral sporotrichosis with fluconazole.

Thirty patients with documented sporotrichosis were treated with 200-800 mg of fluconazole daily. Fourteen patients had lymphocutaneous infection; only five (36%) of these patients had any underlying illnesses. Sixteen patients had osteoarticular or visceral sporotrichosis; 12 (75%) of these patients had underlying diseases, mostly alcoholism, diabetes mellitus, and chronic obstructive pulmonary disease. Eleven of the 30 patients had relapsed after prior antifungal therapy. Most patients were treated with 400 mg of fluconazole; however, four received 200 mg of fluconazole daily for the entire course, and four received 800 mg of fluconazole daily for a portion of their therapy or for the entire course of therapy. Fluconazole therapy cured 10 (71%) of 14 patients with lymphocutaneous sporotrichosis. However, only five (31%) of 16 patients with osteoarticular or visceral sporotrichosis responded to therapy; the conditions of two of these five patients improved only, and there was no documented cure of their infections. With the exception of alopecia in five patients, toxic effects were minimal. Fluconazole is only modestly effective for treatment of sporotrichosis and should be considered second-line therapy for the occasional patient who is unable to take itraconazole.

Adult↗

Role of azoles in antifungal therapy.

The addition of itraconazole and fluconazole to the antifungal armamentarium has resulted in less toxic, easily administered therapy for both endemic and opportunistic mycoses. Itraconazole has become the treatment of choice for most patients with mild-to-moderate histoplasmosis, blastomycosis, and sporotrichosis. Coccidioidomycosis is effectively treated with either itraconazole or fluconazole; fluconazole has become the drug of choice for the treatment of coccidioidal meningitis. In several large cooperative trials, fluconazole has been shown to have a useful role in the treatment of patients with candidemia, localized forms of mucocutaneous and visceral candidiasis, and cryptococcal meningitis.

Antifungal Agents↗

Achromobacter xylosoxidans bacteremia: report of four cases and review of the literature.

Seventy-seven cases of bacteremia due to Achromobacter xylosoxidans were reviewed, and susceptibility studies were performed on 11 clinical isolates of A. xylosoxidans. Nosocomial bacteremia was noted in 54 of 77 patients (70%), and 28 (36%) had infection associated with an outbreak or acquired from a discrete point source. The most common underlying illnesses were malignancies (30%) and cardiac disease (21%); immunosuppression affected 27%. The most common clinical syndromes were primary and catheter-associated bacteremia (19% each) and pneumonia (16%). The case-fatality rate was 30%; only 3% of patients with primary or catheter-associated bacteremia died, but 65% of patients with meningitis, endocarditis, and pneumonia died. The case-fatality rate in neonates was 80%. Susceptibility studies showed that all strains were resistant to aminoglycosides, most were resistant to quinolones, and all were susceptible to broad-spectrum penicillins, imipenem, ceftazidime, and trimethoprim-sulfamethoxazole. Two-disk approximation and time-kill studies showed synergy or additive effects for the combination of gentamicin and piperacillin against most strains.

Adolescent↗

Fluconazole therapy for histoplasmosis. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

We assessed the efficacy of oral fluconazole (200-800 mg daily) in the treatment of non-life-threatening acute pulmonary histoplasmosis, chronic pulmonary histoplasmosis, or disseminated histoplasmosis in patients without human immunodeficiency virus infection. Of 27 evaluable patients, two had progressive acute pulmonary histoplasmosis, 11 had chronic pulmonary histoplasmosis, and 14 had disseminated histoplasmosis. Median durations of treatment in each of the three groups were 6 months, 7 months, and 11 months, respectively. Nineteen patients were treated with 400 mg of fluconazole daily (two of these patients received 800 mg daily for a portion of their treatment courses), seven were treated with 200 mg daily, and one was treated with 800 mg daily. Treatment was successful in 17 (63%) of 27 cases. Both of the patients with acute pulmonary infection responded to therapy, as did five (46%) of 11 patients with chronic pulmonary infection and 10 (71%) of 14 patients with disseminated infection. No substantial toxicity was observed. We conclude that fluconazole therapy for histoplasmosis is only moderately effective and should be reserved for patients who cannot take itraconazole.

Female↗

Identification of chromosomal location of mupA gene, encoding low-level mupirocin resistance in staphylococcal isolates.

Low- and high-level mupirocin resistance have been reported in Staphylococcus aureus. The expression of plasmid-encoded mupA is responsible for high-level mupirocin resistance. Low-level mupirocin-resistant strains do not contain plasmid-encoded mupA, and a chromosomal location for this gene has not previously been reported. We examined high- and low-level mupirocin-resistant S. aureus strains to determine if mupA was present on the chromosome of low-level-resistant isolates. Southern blot analysis of DNA from four mupirocin-resistant strains identified mupA in both high- and low-level mupirocin-resistant strains. Low-level mupirocin-resistant strains contained a copy of mupA on the chromosome, while the high-level mupirocin-resistant isolate contained a copy of the gene on the plasmid. PCR amplification of genomic DNA from each mupirocin-resistant strain resulted in a 1.65-kb fragment, the predicted product from the intragenic mupA primers. This is the first report of a chromosomal location for the mupA gene conferring low-level mupirocin resistance.

Anti-Bacterial Agents↗

Alopecia associated with fluconazole therapy.

OBJECTIVE: To describe the association between fluconazole and reversible alopecia. DESIGN: A retrospective survey of 1) patients enrolled in NIAID Mycoses Study Group (MSG) protocols involving the long-term use of fluconazole for treatment of endemic mycoses and 2) patients treated with fluconazole outside of a protocol setting but by the MSG investigators who were MSG members. SETTING: 26 MSG sites in the United States. PATIENTS: 33 patients with various deep and superficial mycoses who developed alopecia while receiving fluconazole. RESULTS: 11 of 26 investigators reported a total of 33 patients with substantial alopecia related to fluconazole therapy. Underlying mycoses included blastomycosis, sporotrichosis, histoplasmosis, cryptococcosis, coccidioidomycosis, and mucosal candidiasis. In separate MSG studies, 17 of 136 (12.5%) and 8 of 40 (20%) patients had substantial reversible alopecia associated with fluconazole therapy. Eight patients who were not in the protocol had similar adverse effects. Twenty-nine of 33 patients (88%) received at least 400 mg of fluconazole daily for a mean of 7.1 months. Alopecia developed a median of 3 months after initiation of fluconazole therapy and involved the scalp in all patients. Other sites were involved in about one third of patients. Three patients required wigs because of extensive hair loss. Alopecia resolved within 6 months of discontinuation of fluconazole therapy or reduction of the daily dose by at least 50%. CONCLUSIONS: Alopecia appears to be a common adverse event associated with higher-dose (400 mg/d) fluconazole given for 2 months or longer. This effect may be severe but is reversed by discontinuing fluconazole therapy or substantially reducing the daily dose.

Adult↗

Susceptibility of ciprofloxacin-resistant staphylococci and enterococci to clinafloxacin.

Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis obtained from the Ann Arbor Veterans Affairs Medical Center within the last decade were tested for susceptibility to ciprofloxacin and clinafloxacin. For MRSA isolates, the minimum inhibitory concentrations (MICs) of ciprofloxacin were several fold higher than those noted with clinafloxacin. Prior to the introduction of the fluoroquinolones (1984-1985), all MRSA isolates were susceptible to ciprofloxacin and clinafloxacin. By 1993, virtually all MRSA isolates were resistant to ciprofloxacin and a 50-fold increase in the MIC50 and MIC90 for clinafloxacin was seen. In 1985-1986, most enterococcal isolates were susceptible to ciprofloxacin and clinafloxacin. By 1993, one-third of all enterococci were resistant to both ciprofloxacin and clinafloxacin. Fluoroquinolone resistance developed more quickly in enterococci that demonstrated high-level gentamicin resistance. Thus, cross-resistance between clinafloxacin and ciprofloxacin was seen; however, the lower MICs of clinafloxacin for MRSA may allow the use of this drug for some MRSA infections.

Anti-Infective Agents↗

Saccharomyces cerevisiae infections and antifungal susceptibility studies by colorimetric and broth macrodilution methods.

Saccharomyces cerevisiae was isolated in large numbers from operative specimens from two patients with perforated bowel and peritonitis and from the blood of another patient treated with extracorporeal membrane oxygenation. Susceptibility studies were performed on these three isolates and another 29 isolates that colonized or caused infection in a total of 19 patients seen over the last decade. All isolates had low minimum inhibitory concentration (MIC) values for amphotericin B (MIC90 of < or = 0.02 microgram/ml) and flucytosine (MIC90 of 0.2 microgram/ml), and a broader range of MIC values for itraconazole (MIC90 of 0.8 microgram/ml) and fluconazole (MIC90 of 4 micrograms/ml). A colorimetric method using Alamar blue reagent showed good concordance with the standard broth macrodilution method for amphotericin B, flucytosine, and fluconazole, but less good concordance for itraconazole. Serious infections with S. cerevisiae probably should be treated with amphotericin B, with or without the addition of flucytosine.

Amphotericin B↗

Mupirocin resistance: clinical and molecular epidemiology.

The antistaphylococcal activity of topical mupirocin has made it an attractive agent for the treatment of asymptomatic colonization with Staphylococcus aureus. Increasing use has been associated with the emergence of mupirocin resistance in staphyloccoci, and failure of therapy has been associated with the isolation of strains exhibiting high-level resistance (MIC > 500 micrograms/mL). Fortunately, low-level mupirocin resistance (MIC < 100 micrograms/mL) occurs most commonly. Because a novel gene encoding for mupirocin resistance resides in both low-level and high-level resistant strains, the emergence of low-level mupirocin resistance may not be as epidemiologically insignificant as previously thought.

Bacterial Typing Techniques↗

Treatment of blastomycosis with fluconazole: a pilot study. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

There are few clinical data concerning the use of fluconazole, a triazole antifungal agent with in vitro activity against Blastomyces dermatitidis, in the treatment of human blastomycosis. We conducted a multicenter, randomized, open-label pilot trial comparing two daily doses of fluconazole (200 mg and 400 mg) in the treatment of non-life-threatening, non-CNS blastomycosis. Twenty-four patients were enrolled in the study, and 23 patients were evaluable for efficacy analysis. Overall, treatment of 15 (65%) of 23 patients was successful, including eight (62%) of 13 who received 200 mg daily and seven (70%) of 10 who received 400 mg daily. The mean duration of therapy for successfully treated patients was 6.7 months. Of the six patients whose prior antifungal therapy had failed, all six eventually responded to fluconazole treatment. We conclude that fluconazole (200 mg to 400 mg daily) given for at least 6 months is moderately effective treatment for blastomycosis.

Adolescent↗

Pneumococcal vertebral osteomyelitis.

Vertebral osteomyelitis is an unusual complication of pneumococcal infection. This report describes a patient who presented with back pain and lower extremity weakness after bacteremic pneumococcal pneumonia. Magnetic resonance imaging showed destruction of the L-4-L-5 vertebral bodies and thecal sac compression, and Streptococcus pneumoniae was isolated from an aspirate of the disk space. We found only 10 other cases of pneumococcal vertebral osteomyelitis in a review of the literature. In these 11 cases the presentations were usually subacute, and the onset of back pain was insidious. Elevated erythrocyte sedimentation rates were commonly noted. Computed tomography and magnetic resonance imaging were most helpful in delineating the extent of involvement in patients seen in the last decade. Successful treatment included surgery alone in 2 cases that occurred before the antibiotic era, surgery plus 6 weeks of antibiotic therapy in 1, and antibiotics alone for 4 weeks to 7 months in 5. Two patients seen in the preantibiotic era died.

Aged↗

Old and new therapies for sporotrichosis.

The old therapies for sporotrichosis--saturated solution of potassium iodide (SSKI) and amphotericin B--have largely been supplanted by itraconazole treatment. Although SSKI is effective for the treatment of lymphocutaneous sporotrichosis, it is difficult to administer and is frequently associated with side effects; response rates of >90% are associated with itraconazole therapy for lymphocutaneous sporotrichosis. Patients with osteoarticular sporotrichosis rarely have systemic symptoms and can be effectively treated with a prolonged course of itraconazole, thus obviating the need for intravenous amphotericin B therapy with its associated toxic effects. Pulmonary sporotrichosis in patients infected with human immunodeficiency virus continue to be difficult therapeutic problems, but itraconazole appears to be at least as effective as amphotericin B as treatment for these forms of sporotrichosis.

Amphotericin B↗

Alterations in gastric acidity in patients infected with human immunodeficiency virus.

In a randomized crossover trial, gastric acidity and gastric microbial colonization in 19 men infected with human immunodeficiency virus (HIV) (of whom nine had AIDS) were assessed. Gastric acidity was assessed during a baseline period and following pentagastrin or glutamic acid administration. Only two (22.2%) of the nine patients with AIDS and none of the non-AIDS patients were hypochlorhydric, as determined by maximal acid output. However, 60% and 67% of patients in the HIV-infected and AIDS groups, respectively, had persistently elevated gastric pH values during the baseline period. Both pentagastrin and glutamic acid significantly increased gastric acidity. Gastric colonization with Candida albicans and gram-positive mouth flora was common. Overall, this study demonstrates that many HIV-infected patients have elevated gastric pH values that may lead to alteration in drug absorption. The large degree of intrasubject and intersubject variability observed in gastric pH suggests that, unfortunately, one cannot predict which patients will have elevated gastric pH values.

AIDS-Related Opportunistic Infections↗

Torulopsis glabrata: azole susceptibilities by microdilution colorimetric and macrodilution broth assays.

Fluconazole and itraconazole MICs were determined by both the standard macrodilution method of the National Committee for Clinical Laboratory Standards and a colorimetric broth microdilution method for 140 isolates of Torulopsis (Candida) glabrata obtained over a 15-year period. Using the method of the National Committee for Clinical Laboratory Standards the MICs at which 90% of isolates are inhibited (MIC50) for all isolates were 32 and 1.6 micrograms/ml for fluconazole and itraconazole, respectively. For fluconazole, the MIC90 rose from 16 to > 64 micrograms/ml when the MIC90s for isolates collected from July 1980 to June 1991 were compared with those for isolates collected from July 1991 to March 1995. For itraconazole, the MIC90s for isolates from the same time periods were 0.8 and 3.2 micrograms/ml, respectively. Although for isolates from some non-human immunodeficiency virus-infected patients the MICs rose, most of the high MICs were found for isolates from human immunodeficiency virus-infected patients who had been extensively treated with azole drugs for thrush. The colorimetric method yielded endpoints that were more definitive; concordances within 2 dilutions for the two methods were 87% for fluconazole and 86% for itraconazole.

Antifungal Agents↗

Use of a colorimetric system for yeast susceptibility testing.

We examined the reliability and accuracy of a colorimetric assay using Alamar Blue reagent in the performance of susceptibility tests for Candida albicans. We compared the broth macrodilution method recommended by the National Committee for Clinical Laboratory Standards (NCCLS) with a macrodilution method modified with the Alamar reagent and a microdilution method modified with the Alamar reagent. The MICs of fluconazole and itraconazole for 97 isolates of C. albicans and 3 control isolates were tested. For fluconazole, the Alamar-modified broth macrodilution method yielded 94% (91 of 97) concordance within 2 dilutions compared with the NCCLS method, while the microdilution method yielded 95% (92 of 97) concordance. With Alamar-modified methods for itraconazole, broth macrodilution yielded 97% (94 of 97) concordance within 2 dilutions. MICs obtained by the microdilution method, although tightly nested, were shifted to a higher value when compared with those obtained by the NCCLS method; there was only 77% (75 of 97) concordance within 2 dilutions but 97% concordance (94 of 97) within 3 dilutions. Tests by all methods with quality control strains showed excellent reproducibilities. For fluconazole, the methods modified with the Alamar reagent yielded clear endpoints and excellent correlation for the broth macrodilution and microdilution methods. For itraconazole, the methods modified with the Alamar reagent yielded clear endpoints and were reproducible, but higher MICs were obtained by the microdilution methods compared with those obtained by the NCCLS methods.

AIDS-Related Opportunistic Infections↗