Clinical behavior of implant infections due to Staphylococcus epidermidis.

UNLABELLED: Surgical implants and other foreign material are increasingly used in modern medicine to restore or to improve the function of the human body. Infection of an implant is associated with considerable morbidity due to frequent hospitalizations, surgery and antimicrobial treatment. The underlying mechanism is the formation of a bacterial biofilm on the surface of the implanted body. The recognition and diagnosis of implant infections is essential for further therapy and, above all, the decision to remove and exchange the implant. METHODS: We compared the data of 60 patients with implant infections with those of 60 patients with transient bacteremia caused by Staphylococcus epidermidis. The pathogens isolated from blood were characterized with regard to antimicrobial susceptibility and formation of biofilms using a static microtiter plate model. Wild type skin isolates from non-hospitalized healthy volunteers served as control with regard to antimicrobial susceptibility and biofilm formation. RESULTS: Clinical signs and symptoms, underlying diseases and outcome were not different in either group. However, patients with implant infection had fever over a longer time (mean 12 days versus 3 days, respectively, p < 0.05) and more often positive blood cultures than patients with transient bacteremia (3.1 versus 1.2, p < 0.05). Thrombocytopenia was observed in patients with implant infections but not in patients with transient bacteremia (p < 0.05). Biofilms were formed in 86.4 % of the isolates in implant infection, in 88.8 % in transient bacteremia and in 76.9 % of the isolates from healthy volunteers (not significant). Multi-resistance to penicillin, oxacillin, erythromycin, clindamycin, ciprofloxacin and trimethoprim was more common in the hospital strains than in the wild type strains (75.6 % versus 48.7 %, p < 0.05). CONCLUSIONS: The clinical features of implant infections are indistinguishable from those of transient bacteremia. Persisting fever and multiple blood culture yielding the growth of skin flora bacteria are strong indicators for infection of implanted material. Biofilm formation and antimicrobial multi-resistance, as common in implant infection as in transient bacteremia, seem to be accessory factors in infections due to Staphylococcus epidermidis.

[Left ventricular dysfunction in Churg-Strauss syndrome]. / Linksventrikuläre Dysfunktion im Rahmen von Churg-Strauss-Syndrom.

Churg-Strauss syndrome is a rare disorder characterized by hypereosinophilia and a systemic vasculitis occurring inpatients with asthma and allergic rhinitis. Vasculitis commonly affects the lungs, the heart, the skin, and the peripheral nervous system. Cardiac involvement is characterized by acute and constrictive pericarditis, myocarditis and endocarditis, as well as ischemic cardiomyopathy. Endomyocardial fibrosis similar to Loeffler's syndrome has been rarely described. In the presented case, a 43 year old man with a history of allergy and asthma suffered from increasing dyspnea, fever, pulmonary infiltates and cardiomyopathy. Laboratory studies were notable for marked hypereosinophilia. In a bronchoscopic lavage and transbronchial biopsy eosinophilic infiltrates accompanied by vasculitis were found, Churg-Strauss syndrome was diagnosed. Echocardiogram showed endomyocardial deposits in the apex of the right ventricle, right ventricular function was normal particular in the basal segments. The left ventricle was slightly enlarged and left ventricular function was impaired. The diastolic mitral in-flow showed a restrictive pattern. Additionally, a pericardial effusion was observed without signs of tamponade. The patient received corticosteroids, cyclophosphamide and cardiomyopathy-specific therapy and showed a marked improvement after 4 months.

Effect of preoperative prophylaxis with filgrastim in cancer neck dissection.

BACKGROUND: Cancer surgery is known to lead to a deterioration in host defence mechanisms and an increase in susceptibility to infection after operation. Filgrastim enhances important antimicrobial functions of neutrophils including chemotaxis, phagocytosis and oxidative killing mechanisms. METHODS: The effects of additional (all patients received perioperative 3 ' 25 mg kg-1 cefotiam and 1 ' 20 mg kg-1 metronidazole) preoperative prophylaxis with filgrastim (5 microg kg-1 12 h prior to surgery plus 5 microg kg-1 0 h prior to surgery) on neutrophil phagocytosis and reactive oxygen radical production and postoperative infections in 24 patients undergoing cancer neck dissection were studied. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labelled Escherichia coli and Staphylococcus aureus by flow cytometry. Reactive oxygen generation after phagocytosis was estimated by determining the amount of dihydrorhodamine 123 converted to rhodamine 123, intracellularly. RESULTS: In the filgrastim-treated patients a higher neutrophil phagocytic capacity was seen intraoperatively, and 1-5 days postoperative, but not prior to surgery. Reactive oxygen radical production was significantly higher in filgrastim-treated patients prior to surgery, intraoperative and postoperative (1-5 days). 2/12 (17%) patients had postoperative infections in the filgrastim group and 9/12 (75%) patients had infections in the placebo group (P < 0.001). In particular, wound infections were recorded more often in the placebo group (1/12 vs. 6/12; P = 0.004). CONCLUSION: We conclude that filgrastim enhances perioperative neutrophil function and could be useful in the prophylaxis of postoperative wound infections in patients undergoing cancer neck dissection.

Ticlopidine induced prolonged leucopenia in a patient with immunocytoma and chronic hepatitis C.

Ticlopidine is increasingly used in the secondary prophylaxis in patients with arterial occlusive diseases. Neutropenia is a well known side effect of this drug. We report a case of a 73 year old woman who was admitted because of severe prolonged ticlopidine induced leucopenia. The past medical history included an immunocytoma of the IgM-kappa type diagnosed seven years ago with less than 10% infiltration of the bone marrow and a chronic hepatitis C. On admission the white cell count was 1000/microL. Ticlopidine was stopped. The white cell count did not increase within one week, thus filgastrim was applied on two consecutive days. The leucocyte count promptly increased to 6000/microL but consecutively dropped within the next fortnight again to levels below 500/microL forcing daily filgastrim application for another 9 days. Four months after the initiation of the therapy with filgastrim the patient had a white cell count of 4300/microL. We therefore conclude that in patients with a history of potentially bone marrow suppressing diseases the use of ticlopidine has to be carefully weighed against possible myelosuppressive effects.

Beneficial effects of protease inhibitors on body composition and energy expenditure: a comparison between HIV-infected and AIDS patients.

OBJECTIVES: (i) To investigate whether protease inhibitor (PI) (nelfinavir)-containing highly active antiretroviral therapy (HAART) affects body composition differently in HIV-infected and AIDS patients without wasting syndrome. (ii) To delineate the changes in resting energy expenditure (REE) under PI therapy, and to determine whether sustained reductions in HIV RNA would decrease REE. DESIGN: Prospective longitudinal cohort study with individually matched healthy controls. SETTING: Tertiary care centre at a University Hospital. METHODS: HIV-seropositive (n = 20) and AIDS patients (n = 17) with a plasma viral load of at least 10000 copies/ml and 37 healthy volunteers were enrolled. All participants were weight stable, free of acute opportunistic infections, and naive to PI therapy. Patients underwent testing of bioelectrical impedance analysis (BIA), indirect calorimetry and food intake, shortly before the initiation of HAART and 24 weeks thereafter. RESULTS: Both patient groups gained weight, body mass index (BMI), and fat-free mass (FFM) (P < 0.05 versus baseline), whereas only AIDS patients gained fat mass. Increases were more pronounced in the AIDS group. REE was elevated compared with corresponding controls at baseline, and decreased similarly in HIV and in AIDS patients during PI therapy (P < 0.05). The reduction in the viral burden preceded the decrease in REE by several weeks. CONCLUSION: Body composition and metabolic parameters improved during PI therapy in HIV-infected and AIDS patients without wasting. Although an early reduction in viral load as a result of HAART does not seem to influence REE directly, sustained viral load suppression may promote a decrease in energy expenditure.

Effect of polyclonal immunoglobulins on neutrophil phagocytic capacity and reactive oxygen production in patients with gram-negative septicemia.

The effect of immunoglobulin (Ig) preparations on neutrophil phagocytic ability and oxidative burst in response to Escherichia coli stimulation was analyzed in 14 patients with gram-negative septicemia by an ex vivo whole blood assay using flow cytometry. In patients, neutrophils exhibited a decreased capacity to phagocytize E. coli and generate reactive oxygen products compared to healthy controls (median -68%, P < 0.01). The addition of both 7S-Ig and 19S-Ig enriched preparations in vitro resulted in a dose-dependent increase in neutrophil reactive oxygen production at concentrations of 10 g/l (median +153% and +211%, P < 0.01, respectively) and 20 g/l (median +205% and +282%, P < 0.01, respectively). A decreased neutrophil phagocytic ability was seen in patients with septicemia (median -58%) compared to healthy controls (P < 0.01). Again, the addition of 7S and 19S-Igs enhanced the phagocytic ability in a dose-dependent manner (10 g/l: median +56 and +126%; 20 g/l: median +126% and +165%, P < 0.01 for all). It can be concluded that both polyclonal Igs can increase depressed neutrophil reactive oxygen production and neutrophil phagocytosis in patients with gram-negative septicemia.

Human immunodeficiency virus: post-exposure prophylaxis.

Post-exposure prevention is a combined modality approach to reducing HIV transmission. The recommendations are based on the risk of local prevalence and on the likelihood of transmission. In the light of the severe consequences of HIV infection, post-exposure prophylaxis after occupational exposure should be recommended. The medication, consisting of a potent antiretroviral combination (two nucleoside analogues and one reverse transcriptase inhibitor), should be available within two hours.

Effect of pentoxifylline on cytokine patterns in the therapy of complicated Plasmodium falciparum malaria.

The effect of pentoxifylline (PTX) was tested for its capacity to modulate cytokine responses during therapy of severe Plasmodium falciparum malaria in a placebo-controlled, randomized study in 45 adult patients in Bangkok, Thailand. The patients received standard antimalarial treatment with artesunate (120 mg intravenously given immediately, then 60 mg every 12 hr for a total dose of 600 mg). The patients received either low-dose PTX (20 mg/kg/day, n = 15), high-dose PTX (40 mg/kg/day, n = 15), or placebo (n = 15) as continuous infusion for the first three days of antimalarial treatment. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were markedly elevated in all patients prior to treatment. After 6 hr of high-dose PTX treatment, TNF and IL-6 levels significantly decreased while an increase in TNF and IL-6 levels was seen after 6 hr of low-dose PTX or placebo treatment (P < 0.01). After 12 and 24 hr of high-dose PTX infusion, TNF-receptor plasma concentrations were lower than in low-dose PTX- or placebo-treated patients (P < 0.01), whereas no differences between the groups with regard to IL-6 receptor levels were observed. We conclude that 40 mg/kg/day of PTX reduces plasma levels of TNF, IL-6, and TNF-receptor in patients with severe malaria. Whether this reduction improves clinical outcome remains to be determined.

Complement activation in severe Plasmodium falciparum malaria.

We determined indices of plasma complement activation (C3, C4, Bb, C4d, iC3b, and SC5b-9), levels of tumor necrosis factor (TNF) and interleukin-6, and the APACHE II score in 23 patients with complicated Plasmodium falciparum malaria. On admission, plasma concentrations of Bb, SC5b-9, and C4d were markedly increased compared to healthy control subjects (n = 24) (4.5 +/- 1.9 vs 1.5 +/- 0.6 mg/L; 1125.7 +/- 496.9 vs 183.2 +/- 76.5 microg/L; and 15.7 +/- 5.7 vs 7.2 +/- 1.4 mg/L, P < 0.01 for all). In contrast C3 and iC3b concentrations were decreased (631.4 +/- 247 vs 947.3 +/- 243.2 and 105 +/- 17.9 vs 151.3 +/- 14.5 mg/L; P < 0.01 for both). Plasma C4 concentrations in malaria were not different from normal controls. Plasma Bb, C3, and iC3b levels normalized on day 7 of treatment, whereas SC5b-9 and C4d levels remained elevated. A significant correlation between elevated TNF levels and Bb (r = 0.507) and SC5b-9 (r = 0.448, P < 0.01 for both) and a negative correlation between iC3b and SC5b-9 and TNF levels existed (r = -0.537 and r = -0.466, P < 0.01 for both). In addition, a significant correlation between C3 and iC3b (r = 0.689) and C4 and C4d (r = 0.737) existed. However, no relation between clinical disease severity and complement fragments existed. The results demonstrate that both the classical and the alternative pathways of the complement system are profoundly activated in complicated malaria.

Prospective randomized comparison of cefodizime versus cefuroxime for perioperative prophylaxis in patients undergoing coronary artery bypass grafting.

The effects of cefodizime and cefuroxime on neutrophil phagocytosis and reactive oxygen production in 54 patients undergoing elective coronary artery bypass grafting were studied. Both drugs were administered twice at a dosage of 40 mg/kg of body weight (pre- and intraoperative). Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled Escherichia coli and Staphylococcus aureus by flow cytometry. Reactive oxygen generation after phagocytosis was estimated by determining the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. In both groups the mean phagocytic ability for E. coli and S. aureus decreased during surgery (-21 and -8%, respectively, for the cefodizime group and -39 and -38%, respectively, for the cefuroxime group; P < 0.05 for all). In the cefodizime group a normalization of mean E. coli and S. aureus neutrophil phagocytosis was seen on day 5 (+9 and -4% compared to preoperative values; P > 0.35 for both), whereas in cefuroxime-treated patients phagocytic ability remained depressed (-37 and -31%; P < 0.04 for both). In both groups mean neutrophil reactive oxygen intermediate (ROI) production after E. coli and S. aureus phagocytosis increased during cardiopulmonary bypass (+44 and +83%, respectively, in the cefodizime group and +58 and +73%, respectively, in the cefuroxime group; P < 0.05 for all). One day after surgery E. coli- and S. aureus-driven neutrophil ROI production was not different from the preoperative values (-2 and +12%, respectively, for the cefodizime group and +7 and +15%, respectively, for the cefuroxime group; P > 0.15 for all). Postoperative serum levels of the C-reactive protein on days 2 and 7 were lower in cefodizime-treated patients (19 +/- 6 and 4 +/- 2 mg/liter versus 23 +/- 6 and 11 +/- 5 mg/liter; P < 0.05 for both). In addition to cefodizime's antimicrobial activity during perioperative prophylaxis, its use in coronary artery bypass grafting can prevent procedure-related prolonged postoperative neutrophil phagocytosis impairment.

The effect of artemisinin on granulocyte function assessed by flow cytometry.

The effect of dihydroartemisinin, artemisinin and artesunate (0.1, 0.5, 5 and 50 mg/L) on phagocytic function and release of reactive oxygen products by neutrophils was studied by flow cytometry. Incubation with dihydroartemisinin, artemisinin and artemether resulted in a decreased capacity to phagocytose Escherichia coli (0.1-50 mg/L: 62-40%, 66-32% and 59-47% of the control values, respectively; P < 0.001 for all). Conversely, the derivatives enhanced the intracellular generation of reactive oxygen intermediates (0.1-50 mg/L: 146-140%, 174-197% and 188-136% of the control values, respectively; P < 0.001 for all). Artemisia derivatives enhance the reactive oxygen response of neutrophils but depress their phagocytic ability at therapeutic blood levels.

Effect of pentoxifylline in vitro on neutrophil reactive oxygen production and phagocytic ability assessed by flow cytometry.

Neutrophil granulocytes have been described as agents of defence and destruction. The effect of pentoxifylline on the phagocytic ability and generation of reactive oxygen radicals of neutrophils was studied at concentrations of 1, 10 and 100 mg/L. Flow cytometry was used to study phagocytic ability by measuring uptake of fluorescein-labelled bacteria. The generation of reactive oxygen intermediates was estimated by the quantification of the intracellular conversion of dihydrorhodamine 123 to rhodamine 123. In vitro pentoxifylline treatment diminished neutrophil reactive oxygen production (at 10 mg/L -45% and at 100 mg/L -63%; p < 0.001 for both) and reduced neutrophil phagocytic ability (at 100 mg/L -23%; p < 0.05). Both effects were rapidly reversible after plasma exchange. We conclude that pentoxifylline could decrease oxidative tissue damage by neutrophils in septicaemia or after IV granulocyte transfusion.

Rapid susceptibility testing of fungi by flow cytometry using vital staining.

A 1-h assay for antifungal susceptibility testing measuring the impairment of fungal metabolic activity was developed. Yeast viability was analyzed by flow cytometry with a novel fluorescent probe, FUN-1, which emits a red fluorescence when the yeast is metabolically active. For nine Candida albicans strains tested, this method yielded results comparable to those obtained by the standard M27 procedure for amphotericin B, flucytosine, fluconazole, and ketoconazole. Whether the flow cytometry antifungal susceptibility test results correlate with the in vivo activities of the drugs remains to determined.

Effect of single oral dose of azithromycin, clarithromycin, and roxithromycin on polymorphonuclear leukocyte function assessed ex vivo by flow cytometry.

Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and clarithromycin (8 to 12 mg/kg). Flow cytometry was used to study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled bacteria. Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli (median [range], 62% [27 to 91%] of the control values; P < 0.01) and generate reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01). Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%] of the control values; P > 0.05). Roxithromycin treatment did not affect granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No relation between intra- and/or extracellular concentrations of azithromycin and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons). These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose.

Dysregulation of the polymorphonuclear leukocyte--Candida spp. interaction in HIV-positive patients.

OBJECTIVE: In HIV-infected patients there is an increased frequency of fungal infections. Dysregulation of the response of phagocytic cells to fungal pathogens may be involved. DESIGN: Phagocytosis of Candida spp., consecutive intracellular production of reactive oxygen species, and candicidal activity were analysed in polymorphonuclear leukocytes (PML) from HIV-1-infected patients, who were at stage C3 of the 1993 revised Centers for Disease Control and Prevention classification system, by means of flow cytometry. METHODS: Phagocytic ability was assessed by measuring uptake of fluorescein isothiocyanate-labelled Candida albicans, C. krusei and C. glabrata. Reactive oxygen intermediate production was estimated by the quantity of dihydrorhodamine-123 converted to rhodamine-123 intracellularly. The candicidal effect was assessed by the propidium iodide uptake of killed yeast cells. RESULTS: As compared to PML of healthy, HIV-negative controls, PML of AIDS patients exhibited an increased phagocytic activity and a similar ability to generate reactive oxygen products. In contrast, PML of AIDS patients displayed a decreased candicidal activity (P < 0.05 compared to controls). CONCLUSION: These results suggest that in patients with advanced HIV-1 infection the impairment of non-oxidative killing mechanisms of phagocytic cells may contribute to the high incidence of fungal infections.

Elevated levels of soluble CD14 in serum of patients with acute Plasmodium falciparum malaria.

Serum sCD14, tumour necrosis factor-alpha (TNF-alpha), IL-6, and endotoxin were analysed in 45 patients with complicated malaria, in 14 patients with Gram-negative septicaemia and in 24 healthy subjects by ELISA. Malaria patients with renal failure (n = 16) had higher levels than patients without renal failure (n = 29) (8116 + 1440 micrograms/l versus 9453 + 1017 micrograms/l; P < 0.05) and both had higher levels than patients with septicaemia (6155 + 1635 micrograms/l) and normal subjects (2776 + 747 micrograms/l). A significant correlation between sCD14 and IL-6 (r = 0.756) and TNF (r = 0.822) existed. However, no relation between sCD14 and serum endotoxin or indices of clinical disease severity (parasitaemia, fever, parasite or fever clearance time) was seen. Although the role of sCD14 in malaria remains to be determined, elevated levels may participate in the inflammatory response in complicated malaria.

High-dose catecholamine treatment decreases polymorphonuclear leukocyte phagocytic capacity and reactive oxygen production.

Flow cytometry was used to study phagocytic function (uptake of fluorescein isothiocyanate-labeled bacteria) and release of reactive oxygen products (dihydrorhodamine 123 converted to rhodamine 123) following phagocytosis by neutrophil granulocytes of heparinized whole blood treated with adrenaline, noradrenaline, dopamine, dobutamine, or orciprenaline. Reduced neutrophil phagocytosis and reactive oxygen production were seen at 12 micrograms of adrenaline per liter (72% each compared with control values); at 120 micrograms of noradrenaline (72% each), dobutamine (83 and 80%, respectively), and orciprenaline (81 and 80%, respectively) per liter; and at 100 micrograms of dopamine per liter (66 and 70%) (P < 0.05 for all). At these dosages, neutrophil chemotaxis was reduced to < 50% of control values for all catecholamines. Treatment with catecholamines at lower dosages had no significant effect on phagocytosis or generation of reactive oxygen products or chemotaxis. The phagocytic capacity of granulocytes was related to the generation of reactive oxygen products (r = 0.789; P < 0.05). The results demonstrate that catecholamines have a suppressive effect on the response of phagocytic cells to bacterial pathogens at high therapeutic levels in blood.

Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea.

We conducted a prospective, randomized study to compare the efficacy of oral fusidic acid, oral metronidazole, oral vancomycin, and oral teicoplanin for the treatment of Clostridium difficile-associated diarrhea. Treatment resulted in clinical cure for 94% of the patients who were treated with vancomycin, 96% of those treated with teicoplanin, 93% of those treated with fusidic acid, and 94% of those treated with metronidazole. Clinical symptoms recurred in 16% of patients treated with vancomycin, 7% of those treated with teicoplanin, 28% of those treated with fusidic acid, and 16% of those treated with metronidazole. There was asymptomatic carriage of C. difficile toxin in 13% of patients treated with vancomycin, 4% of those treated with teicoplanin, 24% of those treated with fusidic acid, and 16% of those treated with metronidazole. No adverse effects related to therapy with vancomycin or teicoplanin were observed. Considering the costs of treatment, our findings suggest that metronidazole is the drug of choice for C. difficile-associated diarrhea and that glycopeptides should be reserved for patients who cannot tolerate metronidazole or who do not respond to treatment with this drug.

Increased serum concentrations of the carboxy-terminal-cross-linked telopeptide of collagen type I in patients with acute Plasmodium falciparum malaria.

We determined serum levels of the carboxy-terminal-cross-linked telopeptide and carboxy-terminal propeptide of type I collagen (ICTP and PICP) in 24 patients with acute complicated Plasmodium falciparum malaria prior to and 7, 14, 21, and 28 days after therapy by radioimmunoassay in Bangkok, Thailand. Elevated levels of ICTP were observed in patients (mean +/- SD concentration 16.7 +/- 5.8 ng/ml), compared with normal controls (3.1 +/- 1.3 ng/ml), during the acute phase of the disease. In contrast, serum concentrations PICP were not different between patients and controls (168 +/- 63 and 144 +/- 57 ng/ml, respectively). After therapy serum ICTP concentrations decreased but remained elevated even 28 days after the malaria attack (10.3 +/- 2.9 ng/ml). These findings suggest an increased production or release of ICTP in P. falciparum malaria, which could implicate an alteration of extracellular matrix during P. falciparum malaria.