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Biomedical subjects

B J Guglielmo

Publications and source records attributed to B J Guglielmo.

At least 37 records · Page 2Linked to original sources

Immune globulin therapy in allogeneic bone marrow transplant: a critical review.

Various immune globulin products have been utilized in allogeneic bone marrow transplant (BMT) in an effort to decrease the incidence of cytomegalovirus (CMV) infection, infection due to other pathogens and graft versus host disease (GVHD). Controlled trials regarding the use of prophylactic immune globulin have been reviewed. Differences among products and use of various dosing regimens complicates the comparison of the results of one trial to another. Risk factors, such as donor and recipient CMV serology, GVHD prophylaxis, the use of white blood cell transfusions and conditioning regimens, vary significantly, further complicating the analysis. Autologous BMT patients do not appear to benefit from prophylactic globulin therapy. The effectiveness of immune globulin in the prevention of CMV disease in allogeneic BMT is questionable; other measures, including prophylactic ganciclovir and screening of blood products appear to be of greater value. Immune globulin inconsistently decreases the incidence of infection due to pathogens other than CMV. The best established role for prophylactic immune globulin in allogeneic BMT is in the prevention of GVHD.

Bone Marrow Transplantation↗

The new macrolides. Azithromycin and clarithromycin.

Clarithromycin and azithromycin are among the new generation of macrolides that have recently been approved for use. Compared with currently available antibiotics, these agents may be given less frequently and, in the case of azithromycin, for a shorter duration. In vitro data suggest an antimicrobial advantage of both clarithromycin and azithromycin against atypical mycobacterial and toxoplasmal species and possibly Haemophilus influenzae. The cost of both these agents is substantially higher than that of erythromycin and doxycycline, although the convenience of single-dose azithromycin is appealing compared with a 7-day course of doxycycline for chlamydial urethritis and cervicitis. These agents appear to offer advantages over erythromycin in the treatment of Mycobacterium avium-intracellulare. Additional data are needed to establish their role in other bacterial infections.

Azithromycin↗

Ceftizoxime versus vancomycin and gentamicin in neurosurgical prophylaxis: a randomized, prospective, blinded clinical study.

In a prospective, randomized, blinded study, 826 patients undergoing clean neurosurgical procedures received single intravenous doses of ceftizoxime (2 g) (n = 422) or a combination of vancomycin (1 g) and gentamicin (80 mg) (n = 404) 1 hour before an incision was made. Patients with infected or contaminated wounds and those receiving shunts or other implants were excluded. Primary wound infections occurred within 30 days in five patients in each group and were most common after spinal surgery and procedures through previous incisions. Secondary infections (pneumonias, urinary tract infections, and intravenous line-related bacteremia) occurred in 24 patients in the ceftizoxime group and 25 in the vancomycin/gentamicin group. The infection rates after transsphenoidal procedures (n = 129) were remarkably low in both groups. Ceftizoxime caused no adverse drug reactions, but six patients in the vancomycin/gentamicin group had clinically significant infusion-related hypotension or flushing. Placement of a temporary external drain, use of an operating microscope, preoperative steroids, and diabetes were not associated with increased infection rates. Analysis of routinely encountered ventricular cerebrospinal fluid and simultaneously obtained peripheral blood showed low but detectable levels of all three antibiotics within 2 hours; only ceftizoxime, however, achieved cerebrospinal fluid levels sufficient to inhibit the staphylococcus and Gram-negative bacilli most often associated with postneurosurgical infections. We conclude that ceftizoxime is as effective as vancomycin and gentamicin in neurosurgical prophylaxis but is less toxic and penetrates cerebrospinal fluid better.

Adolescent↗

Treatment of funguria.

We evaluated the use of antifungal agents in the treatment of uncomplicated funguria by reviewing all case reports and studies regarding the treatment of funguria published in the English language from 1960 to 1991 (MEDLINE). Adult patients treated for uncomplicated funguria were included. Patients with fungal pyelonephritis and/or other systemic fungal manifestations were excluded from our analysis. All investigations were assessed for study design, sample size, definition of significant funguria, treatment regimen, inclusion of predisposing risk factors in outcome analysis, end points of therapy, and patient follow-up. Direct comparison of the studies on the use of antifungals in the treatment of uncomplicated funguria was not possible given the differing definitions of significant funguria, inconsistent reporting of risk factors, varying treatment regimens, end points of therapy, and duration of follow-up. Case reports and studies involving antifungals such as amphotericin B bladder irrigation, miconazole nitrate bladder irrigation, ketoconazole, and flucytosine were reviewed. Amphotericin B bladder irrigation appeared to be most effective and ketoconazole the least effective treatment of uncomplicated funguria. Predisposing risk factors, such as the presence of an indwelling urinary catheter, appear to play an important role in the persistence of positive cultures and failure of pharmacologic interventions. Until prospective, well-controlled studies are performed, no recommendation can be made for the treatment of uncomplicated funguria. In symptomatic patients therapy is indicated; however, the best regimen is unknown.

Antifungal Agents↗

Gram-negative sepsis, the sepsis syndrome, and the role of antiendotoxin monoclonal antibodies.

The incidence and mortality, pathogenesis, clinical manifestations, and management of sepsis and the sepsis syndrome are reviewed, and the use of antiendotoxin monoclonal antibodies to treat patients with sepsis is discussed. The sepsis syndrome and septic shock are induced by the presence of endotoxin, a lipopolysaccharide found in the outer membrane of gram-negative bacteria. Proper management of gram-negative sepsis includes appropriate antimicrobial therapy, fluids and electrolytes, nutritional support, administration of vasopressors, and mechanical ventilation if necessary. To date, two antiendotoxin monoclonal antibodies have been produced and subjected to extensive clinical testing. HA-1A, a human cell line-derived monoclonal immunoglobulin M (IgM) antibody that contains only a small fragment of murine protein, was tested in one trial. HA-1A significantly reduced mortality in patients with sepsis and gram-negative bacteremia and produced better resolution of major morbidities than placebo in those patients. E5, an IgM antibody produced entirely via murine monoclonal antibody technology, was evaluated in two trials. Results from the first trial showed that E5 significantly reduced mortality in patients with gram-negative infection who were not in refractory shock. In contrast, results from the second trial did not show any significant reduction in mortality among patients with gram-negative infection who received E5. However, resolution of major morbidities occurred more frequently among E5 recipients in both trials. HA-1A and E5 were both well tolerated in the trials. The cost of therapy is expected to be $3000-$4000 per treatment course. The antiendotoxin monoclonal antibodies represent the next step along the path toward important reductions in morbidity and mortality from gram-negative infection. However, the financial implications of the use of HA-1A and E5 are enormous, and stringent patient selection criteria for administration of these products will have to be developed.

Antibodies, Monoclonal↗

Medication usage patterns in patients with human immunodeficiency virus infection: a comparison of patient-reported medication usage with medical chart review.

Patients infected with the human immunodeficiency virus (HIV) receive numerous medications from multiple providers. As a result, it is important that medication usage is properly documented in each patient's medical record. Lack of adequate documentation may confound a provider's assessment of drug efficacy, potentially leading to an increased incidence of drug interactions and adverse effects. The objective of this study was to determine if discrepancies exist between patient-reported medication usage and that documented in the medical record by healthcare providers. Data were obtained using structured telephone surveys and medical chart review. Study participants were recruited from the University of California, San Francisco Medical Center AIDS Clinic. Results obtained for 41 patients demonstrated discrepancies between patient-reported medication usage and that documented in the medical record ranging from 9 to 92 percent, depending on the class of drug. The largest differences were observed with the "as-needed" class of drugs: benzodiazepines (92 percent), morphine (60 percent), and codeine (56 percent). Differences were also noted for scheduled medications: ketoconazole (54 percent), clotrimazole (45 percent), acyclovir (38 percent), zidovudine (15 percent), and pentamidine (9 percent). These observed discrepancies reaffirm the need for accurate exchange of information between provider and patient to promote the most effective, rational, and safe drug therapy. Careful reviews of medication usage at each visit and use of pharmacy-based medication profiles are potential mechanisms to improve documentation of medication usage in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗

Iodine toxicity secondary to continuous povidone-iodine mediastinal irrigation in dogs.

Mediastinitis is a devastating complication following median sternotomy. Continuous povidone-iodine (PVP-I) irrigation has been advocated as therapy because of its broad antimicrobial spectrum and its apparent safety. However, several recent clinical reports have warned of suspected local and systemic iodine toxicity. The purpose of this study is to determine if significant amounts of iodine can be absorbed systemically via the mediastinum, and if so, what toxicity (local and/or systemic) may result. PVP-I (0.5%) was continuously irrigated into the pericardial sacs of three dogs via catheters for 48 hr. Serial serum and urine iodine levels were determined. The serum steady-state concentration (Css), the rate elimination constant (k), the urinary clearance (Cl), and the serum half-life (t 1/2) for iodine were assessed. Serum electrolytes, Bun, Cr, and arterial pH were measured to assess systemic iodine toxicity. Tissue samples of the heart, pericardium, liver, and kidney were examined histologically for evidence of local or end-organ iodine toxicity. This study demonstrated that the absorption of iodine during continuous mediastinal irrigation with PVP-I follows zero-order pharmacokinetics, just as if it were being given by continuous intravenous infusion. The baseline serum iodine concentration was 145.9 +/- 64.3 micrograms/dl, Css was 29,290 +/- 101.4 micrograms/dl, k was 0.0996 +/- 0.009/hr, Cl was 872.4 +/- 119.3 ml/hr, and t1/2 was 6.22 hr. Urinary excretion of iodine increased in proportion to the serum iodine. Measured serum chloride increased in a linear manner (r = 0.949), while serum Na, K, Bun, Cr, and pH were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Antibiotic prophylaxis in cesarean section.

Several controversies exist regarding the use of antibiotic prophylaxis in cesarean section. Studies have investigated effectiveness, choice of drug, timing, duration, and appropriate route of administration. Efficacy of antibiotic prophylaxis in preventing postoperative endometritis in certain high-risk patients has been well documented. Factors identifying patients at high risk for endometritis include: indigent socioeconomic status, labor prior to cesarean section, rupture of chorioamniotic membranes, and number of vaginal examinations. Although many different antibiotics have been tested, no particular regimen has been found to be superior. Administration of antibiotics after cord clamping reduces the risk of fetal exposure without compromising maternal risk of endometritis. A single dose of ampicillin or a first-generation cephalosporin (e.g., cefazolin or cephalothin sodium) given intravenously provides adequate prophylaxis. No additional benefit has been demonstrated with the use of multiple-dose regimens.

Anti-Bacterial Agents↗

Altered pharmacokinetics of antibiotics during vascular surgery.

Prophylactic antibiotics significantly decrease the incidence of infection in various surgical procedures. Although antibiotics must be administered preoperatively to be effective, it is unknown whether therapeutic concentrations are necessary throughout the operation to prevent infection. Furthermore, the pharmacokinetics of antibiotics during surgical procedures is not well understood. Several factors, including blood loss, fluid redistribution, and changes in renal blood flow may alter the pharmacokinetic disposition of the antibiotic. In a controlled investigation of intraoperative antibiotic pharmacokinetics, cefamandole was studied in eight patients undergoing elective surgery of the abdominal aorta and peripheral vasculature. Both elimination half-life (67 +/- 19 minutes versus 93 +/- 23 minutes) and the volume of distribution (16.8 +/- 5.3 liters versus 25.2 +/- 11.9 liters) increased when compared with the preoperative state. The increased volume may be due, in part, to redistribution of fluid. Plasma concentrations of antibiotic were low at the time of graft placement in those patients with normal renal function. Additional antibiotic dosing may be warranted prior to prosthesis insertion in these patients.

Aorta, Abdominal↗

Effect of surgical blood loss and volume replacement on antibiotic pharmacokinetics.

Antibiotic prophylaxis is used widely to prevent postoperative infection associated with cardiac operations. The influence of perioperative blood loss on antibiotic pharmacokinetics has not been well studied. Plasma cefazolin sodium samples from 8 patients undergoing a cardiac operation were collected postoperatively and analyzed. The results suggest that blood loss has a minimal effect on the elimination of cefazolin and that therapeutic concentrations are maintained without altering the dosage regimen.

Aged↗

Microbiology and antibiotics in infectious abdominal emergencies.

The appropriate treatment of intra-abdominal infection is often confusing and controversial. Much of the controversy is due to the availability of a substantial number of newer, broad-spectrum antimicrobials. An understanding of the spectrum of activity, toxicity, and clinical efficacy of these drugs is critical in the selection of therapy for the treatment of intra-abdominal sepsis.

Abdomen, Acute↗