Magid A. Halim

Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients

The efficacy and safety of oral fluconazole versus a polyene regimen in preventing mycoses in neutropenic patients was compared. Patients with haematological malignancy or bone marrow transplantation received as antifungal prophylaxis either fluconazole 200 mg daily or a regimen consisting of clotrimazole trouches 10 mg twice daily with mycostatin, 500,000 i.u. four times daily, benadryl and cepacol mouthwash. Ninety patients at risk for fungus infection were evaluable. Four of 42 patients (9.5 %; confidence interval 2 %–23 %) on fluconazole and 17 of 48 patients (35.4 %; confidence interval 22 %–52 %) (p<0.01) on the clotrimazole regimen developed a clinically significant fungal infection, including 3 (7.1 %) and 11 (22.9 %) patients respectively who had severe fungal infection, mainly pulmonary aspergillosis. Death directly due to a fungal infection within 100 days of the start of prophylaxis occurred in 2 of 42 patients (4.8 %) and 9 of 48 patients (18.8 %) respectively (p<0.06). Kaplan-Meier analysis showed that the chance of survival on fluconazole was statistically greater than for the clotrimazole regimen (p<0.04). A decrease of candidal colonisation of the gastrointestinal and genitourinary tracts occurred only in patients receiving fluconazole. No significant toxicity occurred. A 200 mg daily dose of fluconazole given to these patients thus appears to be well tolerated and to provide a protective effect against the development of fungal infection and death from severe fungal disease.

Chronic non-A, non-B hepatitis complicated by end-stage renal failure treated with recombinant interferon alpha

Chronic non-A, non-B hepatitis occurs in 50% of Saudi patients with end-stage renal failure and requires long-term hemodialysis since it is a contraindication to renal transplantation. Thirteen patients with biochemical and histological documented chronic non-A, non-B hepatitis (11 with HCV antibodies) entered a double-blind placebo controlled cross-over study, in which Roferon A 3 MU or placebo were administered subcutaneously 3 times weekly after hemodialysis for 6 months. The mean ALT fell significantly from pretreatment levels of 74.7 (95% confidence interval (CI) 54.7, 92.5) (13 patients in the 6-month run-in period) and 66.8 (CI 47.7, 85.8) (7 patients in the run-in period + 6 patients in the placebo period) (difference NS) to 37.6 (CI 21.0, 54.2) during interferon treatment (P < 0.005). In 10/13 patients (77%) ALT levels became normal. In the 6-month follow-up period immediately after therapy, the mean ALT was 45.2 (CI 28.0, 62.0). Although this change was not significant (P = 0.49), only 7 of these 10 patients sustained biochemical remission in the 6-month follow-up period. The corresponding total Histological Activity Index improved from 8.9 (CI 7.5, 10.3), 8.9 (CI 7.2, 10.7) (difference NS) to 6.2 (CI 3.9, 8.5) (P < 0.05; P = 0.052, respectively). Intralobular inflammation and periportal inflammation showed the most significant changes. Five of 13 (39%) and 2/13 patients (15%) had complete resolution of piecemeal necrosis and intralobular inflammation, respectively. Toxic effects of interferon were mild, early and self-limiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic amphotericin B versus fluconazole in the management of antibiotic resistant neutropenic fever — preliminary observations from a pilot, exploratory study

A pilot exploratory study was undertaken to collect preliminary information relating to safety and overall outcome in using intravenous fluconazole (FLUC) for managing antibiotic resistant neutropenic fever (ARNF), with the objective of assessing feasibility of performing a larger prospective controlled study. Patients who were neutropenic from treatment for leukaemia or bone marrow transplantation, received either fluconazole (FLUC) or amphotericin B (AB). Eight of 16 patients (50%) on FLUC and 21 of 25 patients (84%) on AB defervesced; the mean time to defervescence was 11.0 +/- 10.0 days for FLUC compared to 7.7 +/- 6.3 days for AB, and a similar proportion in each treatment group defervesced within 5 days (50% vs. 52%), respectively. Six of 16 patients (37.5%) on FLUC and three of 25 patients (12%) on AB developed overt invasive fungal disease, including pulmonary aspergillosis (FLUC 4 cases, AB 2 cases) and invasive candidiasis (FLUC 2 cases, AB 0 cases). The mean time to these events was 19.5 +/- 13.4 (FLUC) and 9.0 +/- 3.6 (AB) days. The fungal related mortality rates were higher in the FLUC group: five of 16 patients (31%) vs. two of 25 patients (18%) died respectively; the time to fungal death was 43.2 +/- 18.2 (FLUC) and 25.0 +/- 18.4 (AB) days. This tendency towards a more favourable outcome in patients on AB may have been due to absence of prior fluconazole prophylaxis in patients subsequently receiving IV FLUC. Analysis of a small subgroup of patients who had all received prior prophylaxis with clotrimazole only, indicated that a greater number of patients subsequently receiving IV FLUC died from fungal disease (5/16 vs.0/6, P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Histologically advanced chronic hepatitis C treated with recombinant alpha-interferon: a randomized placebo-controlled double-blind cross-over study

Chronic hepatitis C is common in Saudi Arabia and most often presents in an advanced stage. To assess the response of patients to interferon, a randomized placebo-controlled double-blind study was undertaken. All but 1 patient had cirrhosis or fibrosis before interferon. After a 24-week observation period patients received alpha 2a interferon, 3 mega units sc tiw or placebo for 24 weeks, then the opposite treatment for another 24 weeks followed by 24 weeks of observation. Liver biopsies were performed before and after each of the treatment phases. Twenty-two out of 24 patients completed the study. The mean alanine aminotransferase (ALT) levels fell from 150.7 +/- 118.7 units/l to 91.0 +/- 42.6 units/l after 6 months interferon treatment (P = 0.03) but only 3 patients (14%) had complete normalization of mean ALT levels and 4 (18%) had > 50% reduction. The mean hepatitis activity index fell from 12.2 +/- 2.6 immediately before to 11.6 +/- 2.5 just after interferon (P = 0.4). After interferon there was an insignificant raise in 6-month mean ALT. Hepatitis C virus-RNA was positive in all 17 patients tested and remained so after treatment. Side-effects were mild and well tolerated. Alpha interferon 3 mega units tiw for 24 weeks is not an effective treatment of histologically advanced chronic hepatitis C.

In vitro Activity of Quinupristin/ Dalfopristin, RP59500, against Gram-Positive Clinical Isolates

Synercid (quinupristin/dalfopristin, RP59500) is a new water-soluble streptogramin which offers some advantages over the commercially available antimicrobials against drug-resistant gram-positive bacteria. Its in vitro activity was compared with ampicillin, augmentin, penicillin, erythromycin, oxacillin and vancomycin against gram-positive bacteria isolated from clinical specimens. Of the 837 gram-positive bacteria tested 834 (99.6%) were inhibited by < 0.6-4.0 mg/l of Synercid. It had excellent activity against both staphylococci and streptococci, including methicillin-resistant staphylococci and vancomycin-resistant enterococci.

Middle Eastern Respiratory Syndrome Corona Virus (MERS CoV): case reports from a tertiary care hospital in Saudi Arabia.

BACKGROUND AND OBJECTIVES Middle Eastern respiratory syndrome caused by novel coronavirus (MERS CoV) has been a major public health challenge since it was first described in 2012 in Saudi Arabia. So far, there is no effective treatment for this serious illness, which features a high mortality rate. We report an initial experience of the use of ribavirin and interferon (IFN)-α2b in the management of MERS CoV at a tertiary care hospital. DESIGN AND SETTINGS A case series of 6 patients admitted with a confirmed diagnosis of MERS CoV were treated with ribavirin and IFN-α2b in addition to supportive management. The patients’ demographics, clinical parameters, and outcomes were recorded. Fifty-four close contacts of these patients were screened for MERS CoV. METHODS Six patients with MERS CoV infection were included in this study. Four cases featured symptomatic disease, including pneumonia and respiratory failure, while 2 were asymptomatic close contacts of the MERS CoV patients. The MERS CoV infection was confirmed by reverse transcription–polymerase chain reaction detection of the consensus viral RNA targets upstream of the E gene (UPE) and open reading frame (ORF1b) on a sputum sample. The patients’ demographics, comorbid conditions, time to diagnosis and initiation of treatment, and clinical outcomes were recorded. RESULTS Three out of 6 patients who had comorbid conditions died during the study period, while 3 had successful outcomes. The diagnosis and treatment was delayed by an average of 15 days in those patients who died. Only 2 close contacts out of the 54 screened (3.7%) were positive for MERS CoV. CONCLUSION Treatment with ribavirin and IFN-α2b may be effective in patients infected with MERS CoV. There appears to be a low infectivity rate among close contacts of MERS CoV patients.

Breast abscess caused by Brucella melitensis

Cutaneous and soft tissue lesions are uncommon manifestations of brucellosis. Though breast involvement in animal brucellosis is not uncommon, involvement of the breast in human brucellosis is extremely rare. We report a case of breast abscess in a 39-year-old female caused by Brucella melitensis. Treatment with combination of trimethoprim/sulphamethoxazole (TMP/ SMX; cotrimoxazole) and doxycycline for 3 months resulted in clinical cure.

Diagnostic dilemma and therapeutic non-compliance in a case of intracranial tuberculoma

A case of extensive intracranial tuberculoma is presented. The patient had been treated for 5 years with a standard antituberculosis regimen but she had been grossly non-compliant. This had led to emergence of multi-resistant Mycobacterium tuberculosis producing progressive disease and extensive cranial nerve damage and proptosis. The unusual CT and angiographic appearances cast doubt on the original diagnosis and a brain biopsy was necessary. Mycobacterium tuberculosis resistant to isoniazid, rifampicin, ethambutol, ethionamide, pyrazinamide, clofazimine and PAS was cultured from the brain biopsy specimen and from an associated groin abscess. A novel regimen of isoniazid, cycloserine, amikacin and ciprofloxacin produced clinical improvement of symptoms and radiological resolution.

Bone marrow morphologic findings in patients with human immunodeficiency virus (HIV) infection.

The hematologic, histologic and morphologic bone marrow findings of 18 patients with human immunodeficiency virus (HIV) infection were reviewed. The mean age of the patients studied was 27 years; age range was six to 63 years. The main bone marrow morphologic finding was hypercellularity (72%), which was mainly due to megakaryocytic hyperplasia with or without granulocytic or erythrocytic hyperplasia. Naked (denuded) megakaryocytic nuclei, which are considered an indicator of HIV infection, were present in 72% of the bone marrows examined. Reticuloendothelial iron blockade was identified in 78% of cases. Other less frequent findings included erythrocytic dysplasia (44%), plasmacytosis (28%), nonspecific granulomas (17%), Hodgkins and non-Hodgkins lymphoma (17%), lymphocytic aggregates (11%) and histiocytosis (6%) . The bone marrow findings in this series of HIV patients appear to be similar to what has been previously reported from other countries.