Is Listeria monocytogenes an important pathogen for prosthetic joints?

Listeria monocytogenes usually causes meningitis or bacteremia, often in immunocompromised adults, pregnant women, or infants. We report a case of septic arthritis caused by L. monocytogenes in a patient with seronegative rheumatoid arthritis (RA) whose hip replacement was infected. She subsequently died, probably secondary to an adult respiratory distress syndrome, a rare complication of listerial infection. We also reviewed all 18 previously reported cases of septic arthritis caused by L. monocytogenes. The frequency of underlying RA, diabetes, neoplastic disease, and immunosuppressive therapy is prominent, as is the concurrent presence of a previous knee or hip replacement. Thus, the simultaneous presence of immune suppression and certain medical disorders or their treatment and a prosthetic joint should alert the clinician to the possibility that L. monocytogenes is the offending microbial agent. In contrast, in immunocompetent persons the usual Gram-positive cocci such as staphylococci, streptococci, or even pneumococci predominate. Although the outcome of appropriate treatment with penicillin or ampicillin alone (or with an aminoglycoside or trimethoprim/sulfamethoxazole in penicillin-allergic individuals) is usually favorable, complicating medical disorders can lead to death. Cephalosporins are rarely effective antimicrobial agents in patients with listeriosis.

Pyomyositis of the anterior tibial compartment.

Five oncology patients developed bacterial pyomyositis involving the anterior tibial compartment and resulting in compartment syndrome with ischemia and abnormalities of neuromuscular function. All patients were neutropenic and thrombocytopenic, and four were receiving or had recently received cancer chemotherapy. Three infections were due to gram-negative bacilli and two to Staphylococcus aureus. Appropriate antimicrobial therapy and surgical drainage in four patients resulted in the resolution of these infections with good residual muscle function. To our knowledge, primary pyomyositis has never previously been known to cause compartment syndrome.

Spontaneous necrosis of the skin associated with cryofibrinogenemia, cryoglobulinemia, and homocystinuria.

Cryofibrinogenemia has been associated with a variety of skin manifestations including purpura, livedo reticularis, and ulceration. Our patient, who had undergone axillobifemoral bypass 5 years previously, presented following the spontaneous development of a necrotic wound involving the left groin scar. The location of the wound suggested the possibility of underlying graft infection, but indium-111 white blood cell scan and MRI failed to show any evidence of infection. The patient was initially treated with oral antibiotics and outpatient debridement with no improvement. A more aggressive approach with inpatient operative debridement and intravenous antibiotics produced moderate improvement. Three months later, the patient developed an identical necrotic wound in the right groin and subsequently a third lesion involving a scar distant from any of the patient's grafts. No evidence of active vasculitis was seen on microscopic examination of the excised tissues. Cryoglobulin and cryofibrinogen assays were positive, and urinary and plasma homocysteine levels were elevated. The patient was subsequently treated with stanozolol, a low-methionine diet, and outpatient intravenous antibiotics with rapid improvement of her wounds. In patients with spontaneous ulceration of the extremities, particularly when they do not respond appropriately to standard therapy, the possibility of cryoglobulinemia or cryofibrinogenemia should be considered.

Megestrol acetate in patients with AIDS and cachexia.

OBJECTIVE: To study the effects of a megestrol acetate liquid formulation (800 mg/d) on body weight, body composition, caloric intake, and mental outlook in patients with the acquired immunodeficiency syndrome (AIDS) who had cachexia. DESIGN: Twelve-week, multicenter, randomized, double-blind, placebo-controlled trial. SETTING: Multiple clinical centers. PATIENTS: 100 patients with AIDS who had weight loss of 10% or more of ideal body weight were randomly assigned to placebo (n = 48) or megestrol acetate (n = 52). MEASUREMENTS: Caloric intake, body weight, body composition, and sense of well-being. RESULTS: Most patients receiving megestrol acetate had increased caloric intake resulting in body weight gain (mainly fat mass). From baseline to week 8, the megestrol acetate group increased their daily caloric intake by 608 calories, whereas the placebo group increased intake by 134 calories (difference, 474 calories; 95% CI, -68 to 880 calories). Body weight in the megestrol acetate group increased by 3.86 kg from baseline to week 8, although it decreased by 0.46 kg in the placebo group (difference, 4.32 kg; CI, 2.42 to 6.22 kg). At week 8 in the megestrol acetate group, patients gained 3.68 kg in fat mass and those in the placebo group lost 0.28 kg (difference, 3.96 kg; CI, 2.49 to 5.43 kg). Body water, lean mass, and patient survival were not statistically different between treatment groups. Patients treated with megestrol acetate had an increased sense of well-being when compared with patients who received placebo. CONCLUSIONS: This megestrol acetate liquid formulation is well tolerated, increases food intake, results in body weight gain, and improves the sense of well-being in cachectic patients with AIDS.

Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials.

OBJECTIVE: To assess the effect of recombinant human erythropoietin (r-HuEPO) on anemia in patients with the acquired immunodeficiency syndrome (AIDS) who are receiving zidovudine therapy. DESIGN: Combined analysis of four 12-week, randomized, double-blind, controlled clinical trials. SETTING: Multiple centers in the United States. PATIENTS: Two hundred and ninety-seven anemic (hematocrit < 30%) patients with AIDS who were receiving zidovudine therapy. Of the 297 patients, 255 were evaluable for efficacy, but all patients were included in analysis of safety. INTERVENTION: Patients were randomly assigned to receive either r-HuEPO (100 to 200 U/kg body weight) or placebo, intravenously or subcutaneously, three times per week for up to 12 weeks. MEASUREMENTS: Changes in mean hematocrit, transfusion requirement, and quality of life. RESULTS: Sixty-nine percent of patients had endogenous serum erythropoietin levels less than or equal to 500 IU/L, and 31% had erythropoietin levels greater than 500 IU/L. In patients with low erythropoietin levels (< or equal to 500 IU/l), r-HuEPO therapy decreased the mean number of units of blood transfused per patient when compared with placebo (3.2 units and 5.3 units, respectively; P = 0.003) and increased the mean hematocrit from the baseline level (4.6 percentage points and 0.5 percentage points, respectively; P <0.001). Overall quality of life improved in patients on r-HuEPO therapy (P = 0.13). Patients with erythropoietin levels greater than 500 IU/L showed no benefit from r-HuEPO in any outcome variable. Placebo and r-HuEPO recipients did not differ in the incidence of adverse effects or opportunistic infections. CONCLUSION: Therapy with r-HuEPO can increase the mean hematocrit and decrease the mean transfusion requirement in anemic patients with AIDS who are receiving zidovudine and have endogenous low erythropoietin levels (< or equal to 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L.

A recalcitrant, erythematous, desquamating disorder associated with toxin-producing staphylococci in patients with AIDS.

Although staphylococcal infections are common in patients with AIDS, staphylococcal toxin-related disorders have rarely been described. Five cases of a staphylococcal toxin-associated syndrome characterized by prolonged erythema, extensive cutaneous desquamation, hypotension, tachycardia, and multiple organ involvement are described in patients with AIDS. These illnesses were recurrent and recalcitrant with a mean duration of 50 days. Toxic shock syndrome toxin-1-producing staphylococci were isolated from three and staphylococcal enterotoxins B and A from one patient each. Sources of organisms were blood, one patient, and soft tissues and nasal accessory sinuses, two patients each. Three of the five patients died of renal failure and central nervous system abnormalities. One survivor required intubation for respiratory failure. All individuals manifested a marked diminution of CD4+ cells. Other laboratory abnormalities included azotemia and prolongation of partial thromboplastin time. Oliguria occurred in three patients. Thus, this recalcitrant erythematous desquamative disorder appears to be a variant of staphylococcal toxic shock syndrome in certain subsets of immunocompromised individuals.

Arterial infections due to Listeria monocytogenes: report of four cases and review of world literature.

Early diagnosis and successful antimicrobial therapy have diminished the frequency of embolomycotic aneurysms, but infected aortic and small vessel aneurysms, arteriosclerotic plaques, and prosthetic grafts are becoming more common. A broad spectrum of pathogens, including Staphylococcus, Salmonella, Enterobacteriaceae, Pseudomonas aeruginosa, and some unusual organisms, are associated with this change. We treated four patients (three with abdominal aortic aneurysms and one with a prosthetic graft) with arterial infections caused by Listeria monocytogenes. Only seven other cases have previously been recorded in the world literature. Infection is suspected when a palpable or radiographically defined aneurysm is present with an otherwise obscure febrile illness. In about one-third of patients, blood cultures have yielded the pathogen. Newer imaging techniques have helped confirm the diagnosis. These infections are best managed by surgical resection in combination with long-term, appropriate antimicrobial therapy with ampicillin or sulfonamides. Unlike other adult listerial infection, except endocarditis, in arterial infection, immunosuppression and malignancy are not predisposing factors.

Human immunodeficiency virus type 1 antigenaemia is enhanced in patients with disseminated cytomegalovirus infection and deficient T lymphocytes.

We have studied 61 patients with the acquired immunodeficiency syndrome (AIDS) regarding the relationships between disseminated cytomegalovirus (CMV) infection with CMV retinitis, HIV1 antigenaemia and CD4+ and CD8+ T-cell deficiency. HIV1 p24 antigenaemia was present in all patients with CMV retinitis (at a high concentration), but in only 28% of patients without retinitis (at a low concentration). Compared to patients without retinitis, those patients who developed retinitis had lower CD4+ and CD8+ prior to and during AIDS. CMV may contribute to deficiencies of T lymphocytes in patients with AIDS.

Response to treatment with the leukocyte-derived immunomodulator IMREG-1 in immunocompromised patients with AIDS-related complex. A multicenter, double-blind, placebo-controlled trial.

OBJECTIVE: To determine if a 6-month course of therapy with IMREG-1, a leukocyte-derived immunomodulator, slows disease progression in patients with AIDS-related complex. DESIGN: Randomized, double-blind trial. SETTING: Five academic- and three community-based clinics. PATIENTS: Immunocompromised patients (143) with HIV. INTERVENTIONS: IMREG-1 or placebo every 2 weeks (13 doses). MAIN RESULTS: Twelve of forty-eight patients on placebo and 5 of 95 patients on IMREG-1 experienced adverse events (AIDS-defining opportunistic infection or neoplasm, wasting syndrome, HIV-associated encephalopathy, or peripheral sensory neuropathy). Based on an intention-to-treat analysis, Kaplan-Meier event probabilities were 26% for the placebo group and 6% for the IMREG-1 group (P less than 0.001); based on the Cox proportional hazards model, the relative risk for patients on placebo compared with patients on IMREG-1 was 5.1 (95% CI, 1.8 to 14.8). The frequency of symptoms significantly increased from baseline in patients receiving placebo. The mean decrease in CD4+ cells from baseline was 80 x 10(6) cells/L in the placebo group and 29 x 10(6) cells/L in patients on IMREG-1, with 20% (8) and 38% (32) of patients, respectively, showing a trend toward an increase (P = 0.04). In patients receiving IMREG-1, the size and rate of delayed hypersensitivity responses were larger than in the placebo group. CONCLUSIONS: Patients with AIDS-related complex experienced fewer adverse events and constitutional symptoms after IMREG-1 treatment. The slower loss of CD4+ cells and increased size and rate of delayed hypersensitivity responses most likely reflect the effect of IMREG-1 on the immune system. No toxicity related to IMREG-1 administration was observed.

Clinical benefits and recovery of delayed-type hypersensitivity in patients with AIDS-related complex treated with IMREG-1 or placebo.

IMREG-1, an immunomodulatory biological therapeutic, was studied in a placebo-controlled, double-blind, six-month trial in 45 anergic patients with AIDS-related complex (ARC) and 4 with Kaposi's sarcoma, which was followed by compassionate IMREG-1 administration to all subjects. The IMREG-1 group had significantly less AIDS-defining events compared with the placebo group during the randomized trial (6.9 events per 100 person-years vs 43.7 events per 100 person-years, P = 0.018, relative risk 6.33) and the total observation period. Patients receiving IMREG-1 significantly improved their work performance. Nine (41%) of 22 patients in the IMREG-1 group, compared with one (14%) of seven in the placebo group, recovered cutaneous reactivity to tetanus toxoid. At the end of the six-month trial, CD4+ counts were 0.429 x 10(9)/l in the IMREG-1 group and 0.304 x 10(9)/l in the placebo group (P = 0.04). IMREG-1 is a promising therapeutic for HIV-infected patients with symptoms of ARC.