Imipenem resistance in Enterobacter.

Blood cultures obtained on two separate occasions from a 37-year-old male who received multiple antibiotics (including imipenem) for treatment of repeated episodes of intraabdominal abscesses and bacteremia yielded two isolates of Enterobacter with reduced susceptibility to imipenem, extended-spectrum cephalosporins, penicillins and aztreonam. Both isolates were unstable, giving rise to different colony types, each of which produced a single, non-inducible Bush group 1 beta-lactamase (pI = 9.6) that hydrolyzed imipenem. Outer membrane proteins were analyzed but no differences were detected between strains with different levels of imipenem resistance. Three-dimensional tests performed in conjunction with disk diffusion susceptibility tests provided a rapid and convenient means of detecting the production of imipenem-hydrolyzing enzymes by the Enterobacter strains. These isolates provided additional evidence that overproduction of the group 1 cephalosporinase of Enterobacter can contribute to resistance to imipenem.

Epidemiology, pathophysiology and clinical presentation of gram-negative sepsis.

OBJECTIVE: To review the epidemiology and pathophysiology of gram-negative sepsis and the new consensus terminology describing the clinical signs of sepsis. DATA SOURCES: Review of the medical literature and compiled data from animal and clinical trials. PARTICIPANTS: Members of the Society of Critical Care Medicine, American College of Chest Physicians and American Association of Critical-Care Nurses with expertise on the subject of sepsis and its complications. RESULTS: Preconference and general sessions were offered at the National Teaching Institutes of the American Association of Critical-Care Nurses, with the goal of clarifying the epidemiology, risk factors and pathophysiology of gram-negative sepsis. In addition, current terminology and new (1992) consensus terminology describing the clinical signs of sepsis were presented. Special emphasis was placed on the role of the healthcare provider in the prevention and recognition of sepsis and the role of the septic mediators in the septic cascade. CONCLUSIONS: If the incidence of sepsis is to be reduced, the healthcare provider must be aware of the risk factors for sepsis and methods of reducing nosocomial infections. A thorough understanding of the role of mediators and consensus terminology used to describe sepsis, severe sepsis, septic shock and multiple organ dysfunction syndrome is necessary to recognize early or progressive signs of sepsis and to initiate state-of-the-art therapy.

Blastomycosis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.

The role of monoclonal antibodies in the management of gram-negative sepsis. Experience with the E5 antibody.

Immunologic targeting of the mediators of sepsis is a new approach to reducing mortality associated with this often-fatal complication. When sepsis is due to infection with a gram-negative pathogen, endotoxin plays a key role in its pathogenesis. Antiendotoxin antibody E5 binds endotoxin from a broad spectrum of clinically relevant gram-negative bacteria and reduces mortality from endotoxemia and bacteremia in animal models. It seems to be safe to administer to patients with suspected gram-negative sepsis; fewer than 2% of patients experienced allergic-type reactions, a frequency similar to that seen with third-generation cephalosporins. When administered in a dose of 2 mg/kg daily for two days, E5 reduces mortality and improves the outcome of multi-organ failure in patients with gram-negative sepsis, especially when administered before the development of refractory shock. Patients with sepsis of other etiology have not been shown to benefit from antiendotoxin immunotherapy. E5 antibody appears to be an effective agent for the adjunctive treatment of gram-negative sepsis. Further evaluation of E5 antibody is warranted in the treatment of patients with neutropenia, burns, and shock.

A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group.

OBJECTIVE: To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals. PATIENTS: Hospitalized adults with signs of gram-negative infection and a systemic septic response. INTERVENTION: Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later. MAIN OUTCOME MEASURES: Mortality over the 30-day study period, resolution of organ failures, and safety. RESULTS: Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified. CONCLUSIONS: Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated.

Role of monoclonal antibody therapy in the treatment of infectious disease.

The past, present, and emerging roles of immunotherapy, including the use of monoclonal antibodies for diagnosis and treatment, are discussed. Although immunotherapy has been used for more than 100 years, it became less important when antimicrobial agents came into widespread use. In the 1970s investigators began to re-examine immunotherapy for potential use in gram-negative infections. Polyclonal antiserum against the J5 mutant of Escherichia coli (gram-negative lipid A) has been shown to be effective in treating patients with bacteremia and septic shock. The discovery of monoclonal antibodies and the creation of hybridoma technology by the fusion of immortal cells with antibody-producing cells have resulted in the production of large amounts of monoclonal antibodies of desired specificities. More recently, murine monoclonal antibodies have been used clinically for immunosuppression in renal-transplant patients (OKT3 antibody) and for prevention of septic complications in patients with suspected gram-negative infection and evidence of systemic response (E5 IgM antibody). E5 antibody directed against gram-negative bacterial endotoxin has been reported to significantly reduce morbidity and mortality from gram-negative sepsis and to be well tolerated. The application of new treatment modalities such as monoclonal antibodies is expected to enhance the therapeutic options available to treat infectious diseases.

Rhino-orbital cerebral mucormycosis.

Rhino-orbital cerebral mucormycosis is the most common manifestation of mucormycosis. In debilitated or acidotic patients, the presence of necrotic tissue should alert the examiner to the possibility of mucormycosis. Radical operation and proper management with early diagnosis should increase the patient's chance of survival.

Seizure propensity with imipenem.

Five patients with seizures related to imipenem administration are described. The potential of imipenem therapy to cause seizure was further studied in a mouse model and compared with the potential for seizure with penicillin and cefotaxime therapy. Penicillin caused ataxia and seizure at a mean mouse serum level of 5800 microns/mL, cefotaxime at 3400 microns/mL, and imipenem at a much lower serum concentration of 1900 microns/mL. The potent activity of imipenem therapy against bacteria, allowing for a clinical dose of only 2 g/d, is unfortunately offset by its higher propensity to induce neurologic symptoms in humans and mice at much smaller doses than would therapy with penicillin G or the cephalosporins, such as cefotaxime.

Oral ciprofloxacin treatment of infections in geriatric patients.

The efficacy and safety of oral ciprofloxacin (750 mg every 12 hours) in the treatment of infections was evaluated in 84 geriatric patients. Duration of treatment ranged from three to 42 days (for a mean of 10.45 days). Satisfactory responses (cured or improved) were noted in 33 of 34 cases of urinary tract infections (97%); in 11 of 13 cases of lower respiratory tract infections (85%); in four of nine cases of skin and skin structure infections (44%); and in both cases of bone infection and bacteremia. Bacteriological cure rates were 91% of 33 urinary tract infections; 83% of 12 lower respiratory tract infections; 62% of eight skin and skin structure infections; and in both cases of bone infection and bacteremia. Three patients evaluable for clinical purposes were bacteriologically unevaluable. Overall clinical efficacy and bacteriological cure rates were 86% and 85%, respectively. Of the 78 evaluable pathogens isolated, 70 (90%) were eradicated. Adverse reactions occurred in 24 patients (29%) and included candida colonization in eight, gastrointestinal upset in six, dermatologic symptoms in five, and vaginal candidiasis, chest pain, renal failure, tremors, monocytosis, thrombocytosis, and increased serum theophylline level in one patient each. Ciprofloxacin appears to be a safe and effective treatment for infections in geriatric patients. Advantages of the oral form include cost effectiveness and decreased length of hospitalization.

Comparative evaluation of safety and efficacy of cefmetazole and cefoxitin in lower respiratory tract infections.

The efficacy and safety of cefmetazole and cefoxitin were compared in a randomized open-label parallel trial in 68 hospitalized adult patients with lower respiratory tract infections. Of 40 patients evaluable for efficacy, 23/25 (92%) in the cefmetazole group and 13/15 (87%) in the cefoxitin group demonstrated a favourable clinical response. The causative bacteria were eradicated in 30/32 (94%) and 13/14 (93%) of isolates in the cefmetazole and cefoxitin groups, respectively. A total of 51 adverse events was noted in 68 patients: 36 in 26 patients (55%) in the cefmetazole group and 15 in 12 patients (57%) in the cefoxitin group. These events were reversible, and except in one patient who was treated for oral candidiasis, did not require any therapeutic intervention or prolonged hospitalization. Cefmetazole appears to be as safe and effective as cefoxitin in the treatment of lower respiratory tract infections of hospitalized patients.

D-lactic acid measurements in the diagnosis of bacterial infections.

Body fluids suspected of bacterial infection were cultured and examined for the presence of D-lactic acid, a specific bacterial metabolite. We examined 206 patients and 264 specimens. D-Lactic acid was found in concentrations of greater than or equal to 0.15 mM in 11 of 11 infected and 6 of 40 noninfected ascitic fluids, 6 of 6 infected and 4 of 33 noninfected pleural fluids, 4 of 4 infected and 0 of 13 noninfected synovial fluids, and 26 of 27 infected and 2 of 130 noninfected cerebrospinal fluids. The overall sensitivity was 79.7%, and the specificity was 99.5% when the D-lactic acid concentration was at least 0.15 mM. The most important clinical utility of the D-lactic acid measurement appears to be for patients with bacterial infection in various body compartments and in patients who have already received antimicrobial therapy. An elevation in D-lactic acid may indicate the presence of bacterial infection even when cultures are negative.

Soft tissue hematoma as a cause of fever in the adult.

Hematoma as an isolated cause of temperature elevation in adult patients is rarely reported. We describe a patient with a large hematoma involving his right leg that caused significant pyrexia. The computerized axial tomography findings are discussed, as well as the possible mechanisms responsible for the temperature elevation.