Massimo Marroni

Primary brain abscess with Nocardia farcinica in an immunocompetent patient

In this paper, we describe a case of an immunocompetent patient with cerebral nocardiosis. The onset was with loss of strength, paresthesia and focal epilepsy of the left arm. MRI showed on T2-weighted sequences a hyperintense central area of pus surrounded by a well-defined hypointense capsule and surrounding edema; on T1-weighted sequences a hypointense necrotic cavity with ring enhancement following administration of intravenous gadolinium. The patient underwent surgical excision of the abscess but culture from the specimen was negative. After 40 days of empirical antimicrobial therapy he developed neurological deterioration with focal epilepsy. A new MRI documented an enlargement of the hypointense lesion in the right frontal-parietal region. A second craniotomy with drainage of the abscess was performed; cultures yielded Nocardia farcinica. Therapy with trimethoprim/sulfamethoxazole, amikacin and meropenem was given for 35 days, and clinical and radiological improvement was observed. Home therapy was done with oral trimethoprim/sulfamethoxazole. Currently, 5 months from the second surgery, the patient can walk with support and no new episodes of epilepsy occurred. Side effects were absent from therapy. The MRI appearance of the brain lesion has improved, with a decrease in size, surrounding edema and ring enhancement.

Prospective, Randomized, Double-Blind Trial Comparing Teicoplanin and Cefazolin as Antibiotic Prophylaxis in Prosthetic Vascular Surgery

Abstract To compare efficacy, tolerability, and cost of antibiotic prophylaxis with teicoplanin and cefazolin in clean prosthetic vascular surgery, a randomized, prospective, double-blind study was performed at the Vascular Surgery Unit of a tertiary-care university hospital. Two-hundred thirty-eight consecutive patients undergoing elective, clean, abdominal or lower-limb prosthetic vascular surgery were allocated to receive a single intravenous dose of teicoplanin (400 mg) or cefazolin (2 g) at the induction of anesthesia. Surgical-site infections occurred in 5.9% of teicoplanin recipients (4.2% wound infection, 1.7% graft infection) and 1.7% of cefazolin recipients (1.7% wound infection, 0% graft infection) (P=0.195). Other postoperative infections occurred in 10% of teicoplanin recipients (pneumonia 7%, urinary tract infection 3%) and 12% of cefazolin recipients (pneumonia 7%, urinary tract infection 2.5%, bloodstream infections 2.5%). Overall mortality rate was 3.4% in teicoplanin recipients (4 patients) and 2.5% in cefazolin recipients (3 patients). Infective deaths occurred in one patient for each group. The two prophylactic regimens were well tolerated. Cost savings of US

Interferon-Alpha Is Effective in the Treatment of HIV-1–Related, Severe, Zidovudine-Resistant Thrombocytopenia: A Prospective, Placebo-controlled, Double-Blind Trial

52 510 favoring cefazolin were related to the lower acquisition cost (US

Outbreak of infusion-related septicemia by Ralstonia pickettii in the Oncology Department.

1034 vs US

Thoracic aortic graft infection after disseminated tuberculosis

4740) and to the shorter duration of the hospital stay (1762 days vs 1928 days). Cefazolin can still be regarded as the drug of choice for prophylaxis in clean vascular surgery.

Aspergillus flavus Infection of an Aortic Bypass

Thrombocytopenia is relatively common in patients infected with human immunodeficiency virus type 1 (HIV-1), and it occurs in patients belonging to all major risk groups, such as homosexuals, intravenous drug users, and hemophiliacs [1-3]. Thrombocytopenia occurs in 5% to 15% of asymptomatic patients; 6% to 24% of these patients have serious thrombocytopenia (counts < 30 109/L [2, 4]) and clinical bleeding [2, 4, 5]. The general consensus is to not treat patients with less severe thrombocytopenia because of the low risk for bleeding and the possibility of spontaneous remissions [6-9]. However, the treatment of severe thrombocytopenia is mandatory in view of the frequent, serious bleeding manifestations [2, 4, 5]. The mechanism of HIV-1related thrombocytopenia is not completely understood but immunologic mechanisms (antiplatelet antibodies or circulating immune complexes, or both) and megakaryocyte viral infection may play a role [10]. Although the response to treatment of HIV-1related thrombocytopenia does not appear to differ substantially from that observed in adults with idiopathic chronic thrombocytopenia, there are limitations when using conventional therapeutic approaches. Steroids and other immunosuppressive agents (for example, vincristine, cyclophosphamide) [11, 12] can facilitate the development of opportunistic infections or can lead to the flaring up of infectious hepatitis, which is often present in these patients [13, 14]; steroids have also been reported to accelerate the progression of Kaposi sarcoma [15, 16]. Splenectomy enhances the risk for subsequent infection, especially severe sepsis [17], and in some patients a late relapse of thrombocytopenia may occur [18]. High-dose intravenous immunoglobulins represent an effective treatment in most patients, but the effect is short-lasting in almost all of them, and the high costs and the need for intravenous administration limit their use [9, 19]. Finally, alternative approaches, such as dapsone [20], protein A immunoadsorption [21], or anti-rhesus factor IgG [19], have been tested in limited series and uncontrolled studies (or both). It is now well established that zidovudine (azidothymidine) can effectively enhance the platelet count of patients with HIV-1related thrombocytopenia. A remission of thrombocytopenia during zidovudine administration has been shown in several case series [22-24] and in one placebo-controlled, prospective clinical study [25]. However, between 30% and 40% of patients with thrombocytopenia are resistant to full-dose (1000 mg/d) zidovudine treatment [23, 24, 26, 27]. It is not clear that higher doses of zidovudine affect thrombocytopenia [28, 29]; in addition, higher doses are potentially toxic [30]. Some anecdotal reports and small, uncontrolled case series have recently suggested that interferon- can correct the thrombocytopenia of patients with HIV-1 infection [9, 14, 31-33], even in patients not responding to zidovudine treatment [31, 33]. However, no studies have analyzed, under carefully controlled conditions, the efficacy, toxicity, and kinetics of the response to interferon- in patients with zidovudine-resistant, HIV-1related thrombocytopenia. We tested whether interferon- can increase the platelet count in patients with zidovudine-resistant, HIV-1related severe thrombocytopenia and assessed the kinetics of the interferon- effects and the possible toxicity of interferon in association with zidovudine in a randomized, placebo-controlled clinical study. Methods Selection of Patients Patients were considered eligible for the study if they were seropositive for HIV-1 by the enzyme-linked immunosorbent assay and the Western-blot technique and had a platelet count less than 25 109/L on at least two occasions separated by more than 2 weeks. In addition, thrombocytopenia had to be refractory to a 1-month course of full-dose (1000 mg/d) zidovudine treatment and to previous therapeutic attempts with one of the following: corticosteroids, splenectomy, vincristine, danazol, high-dose intravenous IgG, or anti-ID immunoglobulins. The main exclusion criteria were pregnancy or breast-feeding; the acquired immunodeficiency syndrome; concomitant serious diseases not related to HIV-1 infection (cardiomyopathy, seizure, stroke, psychosis); presence of antinuclear, anti-smooth-muscle, antimitochondrial, or anti-liver-kidney microsome 1 antibodies; and granulocyte counts less than 1 109/L or hemoglobin levels less than 80 g/L. Women of childbearing potential were advised to practice effective methods of birth control. Assessment before study included a medical history, physical examination, electrocardiogram, chest radiograph, and the following laboratory tests: measurement of hemoglobin, hematocrit, mean corpuscular volume, leukocyte count, differential leukocyte count, platelet count, serum glucose, blood urea nitrogen, serum creatinine, bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, serologic tests for hepatitis B and C, prothrombin time, activated partial thromboplastin time, bleeding time, and urinalysis. Fifteen consecutive patients satisfying the criteria for entry into the study were enrolled between April and October 1992 in four centers belonging to four different hospitals in Central Northern Italy. Written, informed consent was obtained from each patient before enrollment in the study; the study protocol was approved by the Ethics Committee of the Umbria Region. Treatment Patients were enrolled in a double-blind, crossover, placebo-controlled, randomized study in which they were treated with either subcutaneous lymphoblastoid interferon- (Wellferon, Burroughs Wellcome, Italy) or 1 mL of subcutaneous saline solution (placebo). Therapy was administered to the patients in hospital by specially trained nurses. The treatment code was known only to the nurse, and the doctors, nurses involved in patient management, and the patients were all blinded to the study code. All patients received subcutaneous injections of placebo or interferon-, 3 million units, three times a week for 4 weeks. During the following 4 weeks, they did not receive any injections (washout period); they were then switched to the opposite treatment for another 4 weeks. After treatment discontinuation, patients were followed for a final 4-week period (washout period). Patients were randomly assigned to either sequence of the crossover design. The study lasted 16 weeks; during this time patients were seen weekly for clinical evaluations including a physical examination, a review of subjective complaints, and standard hematologic tests including platelet counts. All patients received, throughout the study period, zidovudine therapy at 200 mg three times a day. Bleeding times, immune studies, and p24 antigen, hematologic, renal, and hepatic tests were done at weeks 0, 4, 8, 12, and 16. Evaluation Criteria The primary end point, established before the beginning of the study, was the variation in the number of circulating platelets. A secondary end point was the clinical response to interferon- treatment, defined as follows: 1) complete response: platelet count more than 100 109/L; 2) partial response: platelet count more than 50 109/L and less than 100 109/L; 3) failure: platelet count less than 50 109/L. A cut-off level of 50 109 platelets/L was chosen to define treatment failure because conventionally hemorrhage is rare when counts are greater than this limit. Other secondary end points included the bleeding time, p24 antigen levels in serum, CD4 and CD8 counts, 2-microglobulin levels in serum, and platelet-associated IgG. Laboratory Data Platelet counts were determined on ethylenediaminetetraacetic acid-anticoagulated venous blood samples by using electronic particle counters (Coulter Counter, STKR, Hialeah, Florida for the four centers). Platelet counts were measured on each patient using the same instrument throughout the study. Bleeding time was carried out according to Mielke and colleagues [34] by the use of a standardized template (Simplate II, General Diagnostics, Morris Plains, New Jersey). The registration of the bleeding time was followed for a maximum of 30 minutes; when the bleeding time exceeded 30 minutes, it was considered to be equal to 30 minutes for the statistical analysis. CD4 and CD8 lymphocyte counts were determined by two-color flow cytometry using monoclonal antibodies (Leu 2-3+, Leu 2+3-; Leu 4+Dr-; Becton Dickinson, Franklin, New Jersey) on whole blood samples. Serum p24 core antigen was determined by enzyme immune assay (New England Nuclear, du Pont, Rockville, Maryland); the least detectable amount with this assay is 4.4 pg/mL of serum. Serum 2-microglobulin was assayed by enzyme immune assay (Behring, Scoppito, Italy). Serum platelet antibodies were detected with the indirect platelet suspension immunofluorescence test [35]. Determinations of hemoglobin, complete blood counts, serum glucose, blood urea nitrogen, creatinine, liver function tests (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, -glutamyltranspeptidase, and total bilirubin), prothrombin time, and activated partial thromboplastin times were carried out according to standard procedures. Data Collection and Statistical Analysis All investigators, nurses, and laboratory personnel involved in patient and sample management were blinded to treatment groups until all end points were determined at the end of the study. First-order carryover identifies the residual effect of a given treatment at the time of the second baseline (before the beginning of the second treatment), whereas second-order carry-over indicates any residual effect of the first treatment at the time of the second treatment. Data required by the study protocol were collected and recorded in case report forms by the investigators at each of the participating centers. The case report forms were then submitted to clinical research personnel at the

Detrimental Effects of High-Dose Dexamethasone in Severe, Refractory, HIV-Related Thrombocytopenia

Hospital acquired blood stream infection by Ralstonia pickettii in 9 cancer patients related to the heparin solution contamination used to flush the central venous catheter.

Liposomal amphotericin B for visceral leishmaniasis in a kidney allograft patient

An 80-year-old man with a large (6 cm) aneurysm of the descending thoracic aorta was treated with a stent-graft endovascular implant in December 2002. A few days later, he presented with fever of unknown origin that continued for 12 months despite extensive diagnostic investigation and several cycles of empiric antibiotic therapy. In July 2003 he was admitted to the hospital because of fever and worsening of his general condition. Examination showed the man was febrile (38°C) and dyspnoeic, with a left scrotal mass. Laboratory investigations showed a white blood cell count of 6·0 10/L with a normal differential, an ESR of 45 mm/h, and mild renal and liver impairment. Blood culture was negative, as were other extensive laboratory tests. The left testis was removed and histological examination revealed the presence of chronic granulomas. A chest computerised tomography (CT) scan confirmed a perigraft endoleak as the cause of the increase in size of the aneurysmal sac (10·5 cm), and the patient was scheduled for a proximal stent-graft extension placement in September 2003. A multislice CT done 7 days after intervention showed total exclusion of the perigraft endoleak but the large aneurysmal sac imprinted and dislocated the oesophagus (figure, A, arrow). After further investigation, Mycobacterium tuberculosis was isolated from blood, urine, and stool specimens. The testis was examined for M tuberculosis and tested positive with the Gen-Probe Amplified M tuberculosis direct test and the BDProbetecET system for M tuberculosis complex. Scanning with Tc-labelled autologous leucocytes showed substantial perigraft accumulation. 2 months later, a CT scan showed an air bubble inside the aneurysmal sac, partly emptied into an aortooesophageal fistula (figure, B, arrow). The patient died at home in December 2003. Although tuberculosis infection of vascular implants is supposed to be very uncommon, it should be considered in elderly patients with fever of unknown origin. Lancet Infect Dis 2005; 5: 251

Bartonella henselae lymphadenitis progressing to hepatosplenic disease with slow clinical response despite early diagnosis and treatment

Unlike the case of staphylococcal toxic shock syndrome, it is not routine practice to obtain cervical or vaginal cultures in the evaluation of presumed invasive GABHS disease. It is possible that asymptomatic vaginal carriage of GABHS is more common than previously appreciated. The question of whether patients who present with invasive GABHS should undergo vaginal culture is raised by this case and warrants further investigation. In addition, the clinical outcome and appropriate management strategy for asymptomatic vaginal GABHS carriage in nonpregnant women is unknown and warrants further study.

High-Dose Fluconazole Therapy for Cryptococcal Meningitis in Patients with AIDS

OBJECTIVE: To report a case of HIV-related thrombocytopenia in which high-dose dexamethasone was ineffective and immunologically detrimental. CASE SUMMARY: A 39-year-old white man with persistent, severe, HIV-1—related thrombocytopenia was admitted for epistaxis, bleeding gums, petechiae, and bruising. Previous unsuccessful attempts to reverse the thrombocytopenia included zidovudine, prednisone, vincristine, interferon alfa, and intravenous immune globulins. Based on previous anecdotal reports of the effectiveness of high-dose dexamethasone in refractory, HIV-related thrombocytopenia, we instituted treatment with intravenous dexamethasone 40 mg/d for four sequential days every 28 days. After three cycles of therapy, the platelet count remained <15 × 109/L; however, the CD4+ lymphocyte count decreased progressively from 1447 × 106/L at baseline to 560 × 106/L three months after the third cycle. Due to persistent, severe thrombocytopenia and bleeding, the patient underwent splenectomy, resulting in normalization of the platelet count. DISCUSSION: High-dose dexamethasone has been proposed as treatment for patients with immune thrombocytopenia as an alternative to chronic oral corticosteroids and claimed to be associated with better effectiveness and fewer adverse effects. The results of this treatment in our patient show that this regimen may not only be ineffective, but may also be immunologically detrimental in HIV-infected patients. Although the deterioration of the immunologic status of our patient cannot be fully attributed to high-dose dexamethasone based on the Naranjo scale, the previous long-lasting stability of CD4+ cells and the temporal relationship of a decrease in the CD4+ cell count coinciding with administration of high-dose dexamethasone suggest a causative role of the treatment. CONCLUSIONS: A possible cause—effect relationship between the treatment and the decrease in the CD4+ cell count suggests that the use of high-dose dexamethasone may not be justified in patients with severe, HIV-related thrombocytopenia.