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Biomedical subjects

W G Merz

Publications and source records attributed to W G Merz.

At least 73 records · Page 4Linked to original sources
PubMed1988

Variation of electrophoretic karyotypes among clinical isolates of Candida albicans.

Orthogonal-field-alternation gel electrophoresis was used to compare clinical isolates of Candida albicans by resolving chromosome-sized DNA molecules into an electrophoretic karyotype. Seven to nine bands were observed among isolates recovered from 17 patients. In addition, 14 distinct electrophoretic patterns were noted among the isolates from these patients. In a given individual, isolates were likely to have identical electrophoretic patterns. Therefore, the electrophoretic karyotype patterns demonstrated by orthogonal-field-alternation gel electrophoresis can be used to designate a strain for epidemiologic studies.

Candida albicans↗
PubMed1988

Systemic infection and colonization with and without prophylactic norfloxacin use over time in the granulocytopenic, acute leukemia patient.

Patients undergoing intensive antileukemic chemotherapy and profound granulocytopenia are susceptible to overwhelming infections, particularly those arising from disease- and therapy-related gastrointestinal tract damage. We have previously demonstrated that the ability to suppress bacterial colonization of this site with oral norfloxacin prophylaxis (400 mg every 12 h) affects the incidence and distribution of aerobic gram-negative bacterial infections and the overall management of infectious complications in this patient population. We have now determined the broad impact of continuous, long-term use of oral norfloxacin on aerobic gram-negative bacterial infection and colonization, overall management of presumed and documented infections during marrow aplasia and emergence of clinically significant antibiotic resistant pathogens during intensive antileukemic chemotherapy. Oral norfloxacin prophylaxis administered throughout the course of induced granulocytopenia continues to afford effective protection by suppressing the development of aerobic gram-negative infections, particularly those arising from the gastrointestinal tract, and preventing the acquisition or emergence of multiply resistant pathogens. A long-range effect of norfloxacin on pathogens colonizing the respiratory tract is also detected, with inhibition of acquired drug resistance occurring at that site as well. For these reasons, norfloxacin continues to be an excellent agent for oral prophylactic use in this patient population.

Administration, Oral↗
PubMed1987

Experimental central nervous system phaeohyphomycosis following intranasal inoculation of Xylohypha bantiana in cortisone-treated mice.

Experimental central nervous system (CNS) phaeohyphomycosis was established in cortisone-treated mice following intranasal exposure to conidia of Xylohypha bantiana (Cladosporium bantianum, C. trichoides). X. bantiana was recovered from the lungs of 78% of intranasally inoculated normal mice sacrificed within the first 3 days of infection and from 15% at day 28. The fungus was not recovered from the brains of normal mice. In contrast, X. bantiana was recovered from only 33% of the lungs of cortisone-treated mice within the first 3 days of infection. However, the fungus was recovered from the brain of 11% of cortisone-treated mice sacrificed or dying over a 28 day period. Histologically and temporally the CNS disease in cortisone-treated, intranasally inoculated mice was consistent with hematogenous dissemination from a primary pulmonary focus.

Animals↗
PubMed1987

Prevention of fungal sepsis in patients with prolonged neutropenia: a randomized, double-blind, placebo-controlled trial of intravenous miconazole.

Patients treated with cytotoxic therapy expected to produce neutropenia lasting two or more weeks were randomly assigned in a double-blind study to receive intravenous miconazole or placebo concomitant with empiric antibiotics to test whether miconazole can prevent fungal sepsis. The study drug was initiated at the time of first fever along with antibiotics and was continued until neutropenia resolved, fungal sepsis occurred, or persistent or recurrent unexplained fever after six or more days prompted substitution of the study drug by amphotericin B. Two hundred eight treatment courses in 180 patients were evaluated. Fungal sepsis occurred in only one patient receiving miconazole compared with eight patients receiving placebo (p = 0.03). Fatal fungal sepsis occurred in four patients receiving placebo and in none of the patients receiving miconazole (p = 0.08). There was no evidence for the development of resistance to polyenes or imidazoles in fungal isolates recovered from patients in this randomized trial or an increase in Aspergillus infections in patients who received miconazole in this randomized trial or in 121 subsequently treated patients who received unblinded use of miconazole. Thus, intravenous miconazole was more effective than placebo in preventing fungal sepsis in patients with chemotherapy-induced prolonged neutropenia.

Adolescent↗
PubMed1987

Favorable outcome of invasive aspergillosis in patients with acute leukemia.

During a 2-year period, 15 of 110 patients (14%) admitted for intensive therapy of acute leukemia associated with prolonged deep granulocytopenia developed documented invasive aspergillosis (IA). Antemortem diagnosis was accomplished in 14, and 13 of 15 (87%) survived the infection. Because of the high success rate, we reviewed the courses of the 15 patients to assess factors associated with this favorable outcome. Eleven presented with pulmonary IA; early symptoms occurred at a mean 21.6 days of granulocytopenia (less than 100/muL) and included refractory fever in 14 and pulmonary signs or symptoms in 11. Primary necrotic chest wall lesions associated with Hickman catheters developed in four at a mean 11 days of granulocytopenia, followed by pulmonary involvement. All 15 patients had chest radiographs during granulocytopenia, with 14 (93%) demonstrating pulmonary infiltrates and/or nodules at a mean 20.6 days of aplasia. Nine patients had lung computerized tomography (CT) scans, revealing nodular infiltrates in one patient and a characteristic zone of low attenuation surrounding a mass-like infiltrate in seven other patients, which was found to be diagnostic of IA. Subsequent CT scans performed during and following bone marrow recovery showed progression to cavitation followed by either complete resolution or minimal pulmonary scarring. Eleven patients developed IA during empiric amphotericin B (Amp-B) therapy (0.5 mg/kg/d) for fever refractory to antibacterial antibiotics. Fourteen patients received high-dose Amp-B (1.0 to 1.5 mg/kg/d), which was started within a mean of 2.2 days of first clinical findings; 13 survived. Ten patients received 5-fluorocytosine in addition to high dose amp-B. Survival was similar regardless of presentation, as 91% with primary pulmonary IA and 75% presenting with chest wall lesions survived. All 13 surviving patients had complete granulocyte recovery at a mean 33.8 days. Nephrotoxicity (creatinine greater than 2.0 mg/dL) was observed in seven patients during therapy for IA, but was transient in all seven. We conclude IA can be successfully treated in the deeply granulocytopenic patient provided that it is recognized and treated early, and provided that antifungal therapy is aggressive and is continued until granulocyte recovery occurs.

Acute Disease↗
PubMed1987

Oral norfloxacin for prevention of gram-negative bacterial infections in patients with acute leukemia and granulocytopenia. A randomized, double-blind, placebo-controlled trial.

We evaluated the effect of norfloxacin, 400 mg given orally every 12 hours, on the prevention of bacterial infections in 68 adult patients who had acute leukemia throughout prolonged courses of granulocytopenia (median, 32 days). Gram-negative infections were documented in 13 of the 33 patients receiving placebo, but only in 4 of the 35 patients receiving norfloxacin; no effect on the frequency of gram-positive or fungal infections was noted. Norfloxacin administration resulted in the suppression of gastrointestinal tract colonization by aerobic bacteria without the development of norfloxacin resistance. Patients receiving norfloxacin developed first infectious fevers later than did those receiving placebo, had more rapid resolution of that fever after systemic antibiotic treatment, and spent less time febrile. Therefore, although no difference was seen in survival duration, we found that the prophylactic administration of oral norfloxacin led to decreases in overall morbidity and gram-negative infections, was well tolerated, and did not predispose to the development of multiply drug-resistant bacteria.

Acute Disease↗
PubMed1987

Aspergillus infections in bone marrow transplant recipients.

Aspergillus infection was studied in patients admitted to the Bone Marrow Transplant (BMT) Service at the Johns Hopkins Oncology Center during a 9-year period. The overall incidence was 4% in 549 patients reviewed. The incidence at autopsy was 12% (21 of 174 patients autopsied). There was no difference in frequency of occurrence in allogeneic compared to autologous BMT recipients. However, all infections in autologous BMT patients (5 of 5) occurred during neutropenia before engraftment. In contrast, 16 of 17 infections in allogeneic BMT patients occurred after engraftment (p = 0.0002). This difference presumably related to differences in duration of neutropenia and immunodeficiency. Age, underlying disease, date of BMT, preparative regimen, remission status, prior treatment, interstitial pneumonitis and concomitant cytomegalovirus infection did not predispose patients to aspergillus infection. Different post-BMT immunosuppressive regimens did not affect the risk for aspergillus infection except that patients who were given cyclophosphamide plus methylprednisolone had a higher incidence of aspergillus infection than those given methotrexate (12% versus 1%, p = 0.03). Acute graft-versus-host disease imposed a slight risk for infection (p = 0.06).

Aspergillosis↗
PubMed1986

Pathologic features in the human alimentary tract associated with invasiveness of Candida tropicalis.

The pathologic features of Candida albicans and Candida tropicalis in 23 consecutive autopsied patients with culture-proven disseminated candidiasis were studied in order to determine the pathologic basis for the greater virulence of C. tropicalis. Disseminated C. tropicalis infection with gastrointestinal invasion occurred only in eight neutropenic patients; whereas, C. albicans infection occurred in nine neutropenic and six nonneutropenic patients. C. tropicalis involved the entire alimentary tract in four of eight patients versus one of fifteen patients with C. albicans. C. tropicalis penetrated to the deep submucosa in six of eight patients with C. tropicalis and four of fifteen patients with C. albicans. Nine of ten patients with submucosal invasion were neutropenic. Invasion of submucosal blood vessels occurred in six of eight patients with C. tropicalis and only two of fifteen patients with C. albicans. All patients with submucosal blood-vessel invasion were neutropenic. A band of tissue necrosis at the advancing mycelial margin was present with C. tropicalis but not with C. albicans. These autopsy findings indicate that the greater virulence of C. tropicalis is related to increased invasiveness in the gastrointestinal tract in susceptible hosts.

Candidiasis↗
PubMed1986

Increased incidence of fungemia caused by Candida krusei.

Candida krusei colonized 12.4% of 868 patients undergoing episodes of therapy-induced granulocytopenia over a 9-year period. The gastrointestinal tract was most frequently colonized, followed by the respiratory tract and urinary tract. Ten patients developed systemic infections with C. krusei; all 10 had two or more positive blood cultures. Nine of the 10 patients were colonized with C. krusei, and 6 were receiving systemic antifungal agents at the time of development of the infection. Seven patients died within 1 month of C. krusei sepsis; systemic candidiasis was seen in the autopsies of the four patients on whom autopsies were performed. Therefore, C. krusei should be recognized as an emerging pathogen in select patient populations.

Adult↗
PubMed1986

Association of reduced total iron binding capacity and fungal infections in leukemic granulocytopenic patients.

Serum total iron-binding capacity (TIBC) was measured serially on 70 patients with acute leukemia throughout the period of chemotherapy-induced granulocytopenia. Fungal infections were documented in 13 of these patients (18.6%), while 41 patients (58.6%) had clinically suspected fungal infections and 16 (22.9%) had no evidence of fungal infections during the granulocytopenia. Documented fungal infection occurred in patients with the greatest reduction in TIBC (P less than .015). Early reduction in TIBC also correlated with a greater risk for occurrence of fungal infection, and the earliest institution of amphotericin B (Amp-B) (P less than .004). Effective antifungal therapy was further associated with a return of TIBC levels toward normal. These data demonstrate that altered iron metabolism during granulocytopenia is associated with the development of fungal infections in compromised patients. Serial monitoring of TIBC, along with other clinical and mycologic findings, may prove useful in developing strategies for predicting patients at risk for developing a fungal infection and directing the appropriate use of empiric therapy with Amp-B.

Acute Disease↗
PubMed1986

Infection management during antileukemia treatment-induced granulocytopenia: the role for oral norfloxacin prophylaxis against infections arising from the gastrointestinal tract.

Aerobic gram negative bacterial infections occur commonly in patients with acute leukemia undergoing intensive chemotherapy-induced bone marrow aplasia, and often arise from the gastrointestinal (GI) tract. The value of oral prophylactic norfloxacin (400 mg every 12 hours) in preventing bacterial infections was determined for 68 adults with acute leukemia by a prospective, randomized, double-blind, placebo-controlled trial. The efficacy of norfloxacin administered prophylactically throughout the course of intensive therapy and deep (less than 100 mm/3), prolonged (median 32 day) granulocytopenia against infections arising from the GI tract was demonstrated by its impact on the clinical manifestations of infection, microbiologically documented gram negative bacterial infections, overall antibiotic management, and GI colonization. Although there was no difference with respect to survival, norfloxacin decreased overall morbidity associated with gram-negative infections, was well tolerated, did not impinge on systemic antibacterial or antitumor therapy, and did not predispose to the development of bacteria resistant either to itself or to multiple other antibiotics. The advantages of norfloxacin relative to other oral agents used for GI prophylaxis and the potential beneficial effects of norfloxacin or overall medical cost are discussed. Oral norfloxacin achieves the goals of GI prophylaxis by effectively suppressing early infection arising from the GI tract and inhibiting GI colonization by multiply resistant pathogens that could give rise to late-onset infections during profound chemotherapy-induced bone marrow aplasia.

Acute Disease↗
PubMed1986

Granulomatous encephalitis caused by Bipolaris hawaiiensis.

We describe a case of granulomatous encephalitis caused by Bipolaris (Drechslera) hawaiiensis in an immunocompetent patient. An 18-year-old man with a seven-month history of seizures and right leg weakness was found by computed tomographic scan to have a left frontoparietal enhancing lesion. Biopsy of the lesion revealed granulomatous inflammation and numerous septate hyphae. Culture of the biopsy specimen yielded a pure culture of B hawaiiensis in four days. Susceptibility studies revealed the organism to be sensitive to amphotericin B (minimal inhibitory concentration [MIC] equals 0.25 mg/L) and miconazole lactate (MIC equals 0.064 mg/L), but resistant to flucytosine (MIC greater than 100 mg/L). No synergy was demonstrated with amphotericin B and flucytosine in vitro. The patient was successfully treated with surgery and systemic and intrathecal amphotericin B therapy, and a negative culture was obtained from a repeated brain biopsy six weeks later.

Adolescent↗
PubMed1985

Improved recovery of group A beta-hemolytic streptococci with a new selective medium.

A new selective group A streptococcus agar (ssA) (BBL Microbiology Systems, Cockeysville, Md.) was evaluated for the recovery and direct plate identification of group A beta-hemolytic streptococci (GABHS) in comparison with sheep blood agar (SBA). A total of 265 GABHS were recovered from 1,116 throat swab specimens on both media, with detection rates of 98.9 and 91.7% for ssA and SBA, respectively. Primary bacitracin disk susceptibility tests were performed on 549 specimens, and presumptive identifications were possible for 81.4% of the GABHS on ssA, as compared with 44.2% on SBA. All of the 120 GABHS recovered from another 567 specimens were identified by a coagglutination method after overnight incubation on ssA, whereas only 70.2% were identified at this interval on SBA. The major advantage of the ssA was the inhibition of normal respiratory flora, permitting improved recovery and rapid identification of GABHS.

Culture Media↗
PubMed1984

Susceptibility testing of filamentous fungi to amphotericin B by a rapid radiometric method.

A rapid, radiometric method was developed to determine the susceptibility of filamentous fungi to amphotericin B. The rapid, radiometric method depended on measurement of the inhibition of 14CO2 production in the presence of amphotericin B. Thirty isolates of filamentous fungi were tested by the rapid, radiometric method and a reference agar dilution method. There was 93% agreement between the two methods when an 80% or greater decrease in CO2 production was used to calculate the minimal inhibitory concentration with the rapid, radiometric method. Minimal inhibitory concentrations, based on 80% decrease of CO2 production, were achieved within 24 h of incubation with all of the fungi tested.

Amphotericin B↗
PubMed1984

Candida lusitaniae: frequency of recovery, colonization, infection, and amphotericin B resistance.

Candida lusitaniae recovered from 58 specimens from 13 patients represented less than 1% of the yeasts isolated over a 15-month period. The majority of isolates were recovered from respiratory tract, stool, and urine specimens. Of the 13 patients, 1 had a documented infection associated with septicema. Urine isolates from that patient developed resistance to amphotericin B during therapy.

Amphotericin B↗