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Biomedical subjects

A G Freifeld

Publications and source records attributed to A G Freifeld.

13 recordsLinked to original sources
PubMed1996

The outpatient management of febrile neutropenia in cancer patients.

Treatment of fever and neutropenia in cancer patients has been recognized for 30 years as a medical emergency, requiring prompt in-hospital evaluation and institution of broad-spectrum intravenous (i.v.) antibiotics. This action was deemed necessary due to the high frequency of life-threatening infections in febrile neutropenic patients, with no way to distinguish patients who are infected from those who are not. In recent years, it has become clear that not all neutropenic cancer patients are at the same level of risk for developing severe infections or life-threatening complications during neutropenia. Those who are at low risk may be candidates for treatment outside the hospital setting, either with i.v. regimens or potent oral antibiotics. The identification of low-risk febrile neutropenic patients and the specific outpatient approaches that have been tested to date are discussed. Outpatient management of fever during neutropenia could obviously be much less costly than standard inpatient care and could improve quality of life for low-risk patients undergoing cancer therapy.

Administration, Oral↗
PubMed1995

A controlled seroprevalence survey of primate handlers for evidence of asymptomatic herpes B virus infection.

Herpes B virus (BV) is a common cause of recurring mucocutaneous infections in monkeys of the genus Macaca. Like its human counterpart, herpes simplex virus (HSV), BV establishes lifelong latency and can be reactivated from infected monkeys symptomatically or asymptomatically. Incidental infection of humans handling BV-shedding monkeys can result in fatal meningoencephalitis. To determine whether humans exposed to infected monkeys can acquire asymptomatic BV infections, 480 subjects were evaluated in a controlled seroprevalence study. Sera from 321 primate handlers, including many with repeated injuries inflicted by Macaca monkeys, and 159 people never exposed to monkeys were tested in blinded fashion by both competition ELISA and Western blot to determine the prevalence of BV and HSV seropositivity. Although 293 persons proved positive for HSV antibodies, no primate handlers or control subjects showed BV-specific antibody responses. There is no serologic evidence that BV causes asymptomatic infections in humans.

Adult↗
PubMed1995

Monotherapy for fever and neutropenia in cancer patients: a randomized comparison of ceftazidime versus imipenem.

PURPOSE: To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia, and to determine whether fewer antimicrobial modifications (additions or changes) are required by the broader-spectrum agent, imipenem. PATIENTS AND METHODS: Adult and pediatric patients undergoing chemotherapy for solid tumors, leukemias, or lymphomas were randomized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection. Comparisons were based on numbers of modifications made to each monotherapy during the course of neutropenia, in patients stratified as having unexplained fever or a documented infection. RESULTS: Among 204 ceftazidime and 195 imipenem recipients, the overall success rate with or without modification was more than 98%, regardless of initial antibiotic regimen. Modifications occurred in half of all episodes, primarily in patients with documented infections on either monotherapy. Antianaerobic agents were more frequently added to ceftazidime (P < .001), but addition of other antibiotics, including vancomycin and aminoglycosides, was similar between the two monotherapy groups. Imipenem therapy was associated with significantly greater toxicity, manifested by Clostridium difficile-associated diarrhea and by nausea and vomiting, which required discontinuation of imipenem in 10% of recipients. CONCLUSION: Ceftazidime and imipenem are both effective in the management of fever and chemotherapy-related neutropenia, provided that modifications are made in response to clinical and microbiologic data that emerge during the course of neutropenia. Imipenem, despite its broader antimicrobial spectrum, does not significantly decrease the overall need for antibiotic modifications and is more often complicated by gastrointestinal toxicity.

Acyclovir↗
PubMed1993

Induction and enhancement of immune responses to herpes simplex virus type 2 in humans by use of a recombinant glycoprotein D vaccine.

A vaccine for a chronic or recurrent viral infection should induce immune responses that protect against primary disease or that augment preexisting defenses sufficiently to diminish the likelihood of disease recurrence or progression. Such a vaccine was sought for genital herpes, a sexually transmitted infection of epidemic proportion. Vaccine containing recombinant herpes simplex virus type 2 glycoprotein D expressed in CHO cells was given repeatedly and safely to 24 human volunteers. In previously uninfected subjects, the vaccine induced primary antigen-specific and neutralizing antibody responses nearing or exceeding those seen at entry in subjects with genital herpes. Primary cellular immune responses were also evoked. Vaccination of previously seropositive subjects boosted antibody titers to levels that remained, for > or = 1 year, severalfold above those attained in recurrent genital herpes. Either the quantity or mode of presentation of antigen permitted this vaccine to exhibit previously unachieved immunogenicity, which may prove adequate for antiviral immunoprophylaxis or treatment of genital herpes.

Adult↗
PubMed1993

Infectious complications in the immunocompromised host. The antimicrobial armamentarium.

The treatment of infectious complications in the cancer patient has evolved as a consequence of the developments in cancer chemotherapy, which significantly impair immune function. Broad-spectrum, single-agent antibiotics have replaced more cumbersome multidrug regimens for empiric coverage of fever and neutropenia in many institutions. The use of new, potent oral antibiotics may be a next step toward further simplifications. Several new antivirals have come into clinical use in the past decade, and reports of viral resistance to the standard agent, acyclovir, have come forth. Increasing experience with new (and older) antifungal and antiparasitic agents has given a better understanding of the use of these drugs for both prophylaxis and treatment. This overview includes a critical appraisal of the attributes and limitations of current antibiotics, antivirals, antifungals, and antiparasitic agents for the immunocompromised host.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Resistance of viruses to antiviral drugs.

In recent years, substantial advances in antiviral therapy have been made; however, in the immunocompromised host, antiviral drug resistance is becoming an issue of increasing clinical importance. Understanding the mechanism of action of antiviral agents, especially those used to treat herpesvirus infections, may enable us to design new therapeutic agents and better treatment regimens to deal with antiviral drug resistance.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Acyclovir suppression of frequently recurring genital herpes. Efficacy and diminishing need during successive years of treatment.

Forty-seven patients with frequently recurring genital herpes participated in one or more of five sequential trials of oral suppressive therapy with 200 mg of acyclovir three times daily from four to 12 months' duration. The prolonged use of acyclovir was extremely well tolerated, and treatment efficacy was sustained through successive studies. Recurrences in eight patients with repeated treatment "failures" were more effectively suppressed with higher doses of acyclovir. All patients experienced recurrent infections after the treatments were completed; however, the mean time to recurrence following each treatment period became progressively longer, and resumption of suppressive therapy was no longer warranted for ten patients. These data indicate the efficacy and safety of chronic suppressive therapy with acyclovir and the value of interrupting prolonged treatment to assess its further need.

Acyclovir↗
PubMed1983

Nontransmural versus transmural myocardial infarction. A morphologic study.

Although "nontransmural" and "transmural" are morphologic terms used widely to distinguish patients with myocardial infarction, controversy exists as to their meaning regarding clinical course. For this study, a transmural infarct was defined as one that involves essentially the full thickness of the ventricular wall, and nontransmural was defined as something less. The purpose of this study was to identify true morphologic nontransmural acute (less than 21 days old) infarcts at autopsy and compare them with transmural (full-thickness) infarcts in age-matched subjects, for clinical and pathologic similarities and differences. Among the autopsy subjects, comparing 35 nontransmural and 35 transmural infarcts, there was no significant difference with regard to subjects' race or sex, chest pain, arrhythmias, heart block, or cause of death; transmural myocardial infarctions did have a higher frequency of new Q waves (30 of 35 versus six of 35, p less than 0.001) and presented more often with increasing dyspnea. At autopsy, there were no significant differences regarding heart weight, location of infarcts, severity of coronary disease, age of acute infarct, or total size of infarct (18 percent of left ventricle for nontransmural versus 22 percent for transmural). There was, however, a significantly greater tendency for those with nontransmural infarct to have evidence of prior infarction at autopsy (27 of 35 versus 19 of 35, p less than 0.05). Acute coronary thrombi in the distribution of the infarct were significantly more common among transmural myocardial infarcts (32 of 35 versus 18 of 35, p less than 0.001). Morphologically, the nontransmural infarcts showed mural involvement ranging from 20 to 90 percent of the left ventricle, and histologically showed more contraction band (i.e., reflow) injury (57 percent with more than 30 percent contraction band necrosis) compared with transmural infarcts (32 percent with more than 30 percent contraction band necrosis) (p less than 0.05). Fatal nontransmural and transmural infarcts have major clinical and pathologic similarities, but differences in number of prior infarcts, type of necrosis, and occurrence of coronary thrombi suggest differing pathophysiology. The heterogeneity of both transmural and nontransmural infarcts likely accounts for existing differences among clinical studies regarding prognosis. Although this classification system has value in the clinical setting, that at times it represents an imprecise oversimplification of infarct type should be recognized in assessing individual patients.

Aged↗
PubMedDate not supplied

Histoplasmosis in solid organ transplant recipients at a large Midwestern university transplant center.

Histoplasma capsulatum sporadically causes severe infections in solid organ transplant (SOT) patients in the Midwest, but it has been an unusual infection among those patients followed at the University of Nebraska Medical Center (UNMC), located at the western edge of the 'histo belt.' Nine SOT patients with histoplasmosis are described (6 renal or renal-pancreas and 3 liver recipients) who developed severe histoplasmosis over a recent 2.5-year period at UNMC. Symptoms started a median of 11 months (range, 1.2-90 months) after organ transplant and consisted primarily of fever, cough, shortness of breath, and malaise or fatigue present for approximately 30 days prior to medical evaluation. All patients had an abnormal chest radiograph and/or computed tomographic scan. Tacrolimus was the main immunosuppressant in all 9 patients, along with prednisone or mycophenolate. Dacluzimab or thymoglobulin had been given around the time of transplant in 6 of 9. None was treated for an episode of acute rejection within 2 months before onset of histoplasmosis, although 2 were on high-dose immunosuppression after recent transplants. Diagnosis was made by culture in 8 of the 9 patients, with positive serum and urine histoplasma antigen tests in all 9 cases. From 1997 to 2001, during a period of relative quiescence of the disease in the general population, the rate of clinical histoplasmosis among SOT patients at UNMC was estimated at 0.11%, whereas during 2002 through the first half of 2004, the rate rose 17-fold to 1.9%. Histoplasmosis can present as a prolonged febrile illness with subacute pulmonary symptoms in a cohort of SOT patients, despite the absence of a regional outbreak.

Academic Medical Centers↗
PubMedDate not supplied

The current state of infectious disease: a clinical perspective on antimicrobial resistance.

The medical community is in the midst of a wake-up call. No longer can antimicrobial use be taken for granted. The overprescribing of antimicrobials has taken its toll and the consequence has been a precipitous increase in drug-resistant pathogens seen over the last decade. Pharmaceutical companies and researchers are no longer able to keep a step ahead of these resistant pathogens with new antimicrobial agents. The primary care clinician is now faced with complicated treatment issues for many infectious diseases that were once considered uncomplicated. The mechanisms leading to the development of antimicrobial resistance in bacteria is discussed in addition to an overview of the most common drug-resistant pathogens.

Bacterial Infections↗