In vitro interaction between clindamycin and trimethoprim in combination on staphylococci.

The in-vitro interaction between clindamycin and trimethoprim was tested on 10 staphylococcal clinical isolates by the checkerboard technique and by the time-kill curve. Indifference was demonstrated against seven of these strains and antagonism against three. The clindamycin/trimethoprim combination is of no value if the purpose of the combination is to obtain synergy against staphylococci. However, the combination is useful against mild polymicrobial infections due to Gram-positive aerobes, anaerobes and Enterobacteriaceae.

Pharmacokinetics of aztreonam in patients with liver cirrhosis and ascites.

The pharmacokinetics of aztreonam were studied in six healthy male subjects (group I) and 12 male patients with post-hepatitis liver cirrhosis and ascites. Patients were allocated into two groups according to serum creatinine; group II included nine patients with serum creatinine. < or = 15 mg/L while group III included three patients with serum creatinine > 15 mg/L. Aztreonam 1 g was given as iv bolus injection. Aztreonam reached a peak concentration in the ascitic fluid (AF) of 6.2 +/- 2.3 mg/L at 4 h, and of 8.7 +/- 4.4 mg/L at 6 h in groups II and III respectively. The level of the drug in AF 24 h post-dosing was still higher than MIC90 for Enterobacteriaceae in most patients. The half-life of elimination from serum increased significantly (P > 0.001) from 1.82 +/- 0.14 h in group I to 6.6 +/- 2.1 h and to 8.87 +/- 0.2 h in groups II and III, respectively. Both the central and the terminal volumes of distribution were higher in cirrhotic patients than in healthy volunteers. Liver cirrhosis and ascites resulted in a significant increase (P < 0.001) of the total body clearance (Cl) of aztreonam from 84 +/- 8 mL/h/kg in group I to 209 +/- 87 mL/h/kg in group II. However, the concomitant association of mild renal impairment in group III abolished this increase; Cl in group III was 122 +/- 50 mL/h/kg. The AUC0-infinity serum was 137.5 +/- 12.2, 78.5 +/- 24.9 and 151 +/- 42 mg.h/L in groups I, II and II, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of cefodizime in patients with liver cirrhosis and ascites.

The pharmacokinetics of cefodizime were studied in 6 healthy male volunteers (group A) and 6 patients with liver cirrhosis and ascites (group B) receiving 1 g of the drug as an i.v. bolus. Cefodizime was assayed in serum and ascitic fluid (AF) samples by a microbiological assay. The serum concentration-time curve fitted a two-compartment open model in group A and a three-compartment open model in group B. Initially, the serum level of cefodizime in group A exceeded that in group B for about 10 h; thereafter the reverse occurred until 24 h post-dosing. Cefodizime penetrated rapidly into the AF, reaching a peak at 6 h, and its AF level was still above the MIC90 for Enterobacteriaceae in most patients at 24 h post-dosing. The half-life of distribution did not differ significantly between the two groups, while the elimination half-life was prolonged significantly (p < 0.001) from 2.7 +/- 0.2 h in group A to 5.4 +/- 0.8 h in group B. The central volume of distribution (Vc) did not differ significantly in the two groups, while the terminal volume of distribution (Vp) was significantly smaller (p < 0.01) in group A (0.172 +/- 0.30 l/kg) than in group B (0.55 +/- 0.20 l/kg). The area under the serum concentration-time curve (AUC0-infinity serum) was significantly larger (p < 0.001) in group A [322 +/- 34 (micrograms/ml).h than in group B (180 +/- 34 (micrograms/ml).h]. The area under the AF concentration-time curve (AUC0-infinity ascites) in group B was 141 +/- 37 (micrograms/ml).h.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum lipoprotein profile under different antihypertensive therapy.

Serum lipids of 80 patients with moderately severe essential hypertension under four different antihypertensive therapies were compared to ten matched hypertensives on a placebo, after eight weeks of therapy. The results in the serum lipid parameters measured after therapy showed with enalapril a significant increase in high-density lipoprotein cholesterol (HDL-C) and a decrease in the total cholesterol/HDL-C ratio. With benazepril a significant decrease in the total cholesterol/HDL-C ratio was obtained. With the diuretic combination Epitens the effect on serum sodium and potassium was minimal. No significant changes were found in the lipoprotein profile following the administration of the placebo. Both angiotensin converting enzyme inhibitors (enalapril and benazapril) induced a significant improvement in the atherogenic ratio; as well as the calcium antagonist (isradipine), though to a less extent. The diuretic Epitens induced an insignificant deterioration of the atherogenic ratio.

Pharmacokinetics of ceftazidime in patients with liver cirrhosis and ascites.

The pharmacokinetics of ceftazidime were studied in 18 male individuals, including six healthy volunteers and 12 patients with liver cirrhosis and ascites. Each participant received 1 g of ceftazidime as a single intravenous bolus injection. The elimination half-life was longer in cirrhotic than in control patients (5.40 +/- 1.02 h) vs. (1.98 +/- 0.24 h), P less than 0.01; probably due to slow return from the ascitic compartment. Nevertheless, total body clearance did not differ significantly between the two groups (81.4 +/- 30.3 ml/h/kg vs. 83.6 +/- 24.9 ml/h/kg). Dose reduction is not necessary when treating systemic infection in cirrhotics. Ceftazidime attained a concentration of 1 microgram/ml in the ascitic fluid in most patients 15 to 30 min after the injection, and maintained this level, which is higher than the MIC90 of Enterobacteriaceae, for 24 h. An intravenous bolus injection of 1 g ceftazidime every 24 h is sufficient to treat patients with spontaneous bacterial peritonitis caused by a susceptible organism other than Pseudomonas aeruginosa.

Otitis externa malignum.

Twelve elderly diabetic patients with Pseudomonas otitis externa malignum were successfully treated with norfloxacin as monotherapy for 2-5 weeks, using 400 mg b.i.d. Patients tolerated the courses with no side effects, except some drowsiness in two patients, and all completed the course. The bacteriological and clinical cure rate was 100%, without resorting to surgery.

Pharmacokinetics of cefodizime in normal individuals and in patients with renal failure.

The pharmacokinetics of cefodizime (HR 221) were studied in 6 healthy male individuals and 12 male patients with various degrees of chronic renal failure following intravenous bolus injection of 1 g of the drug. Serum pharmacokinetics were described by an open two-compartment kinetic model. The serum levels of cefodizime exceeded the MIC90 for Enterobacteriaceae, Haemophilus influenzae and Neisseria gonorrhoeae for more than 12 h in healthy individuals and 24 h in renal failure patients. The half-life of elimination was significantly prolonged (p less than 0.001) from 2.7 +/- 0.2 h in healthy volunteers to 7.7 +/- 1.5 h in renal failure patients. The total systemic clearance decreased significantly (p less than 0.001) from 43.3 +/- 5.8 ml/h/kg in healthy volunteers to 23.2 +/- 5.6 ml/h/kg in renal failure patients. A linear correlation (r = 0.9; p less than 0.001) was found between creatinine clearance and the total systemic clearance of cefodizime. The AUC0-infinity in patients with renal failure was more than double the value in healthy volunteers. An equation to calculate the 1-gram dose interval of cefodizime in patients with compromised renal function is provided.

Experience with interferon in chronic hepatitis B in Egypt.

Forty patients with compensated chronic active hepatitis B and elevated aminotransferases who were HBsAg and HBeAg positive were randomised to a treatment group receiving recombinant interferon alpha-2b (rIFN alpha-2b) or no treatment as a control group. The treated patients were divided into 2 groups, group I (n = 12) received IFN in a dose of 5 MU/m2 thrice weekly by subcutaneous injection for 16 weeks, and group II (n = 8) received the same dose daily for the same duration. Patients were followed up for 12 months after therapy ended. Initiation of IFN therapy was associated with an increase in aminotransferases, reaching a peak at 4-6 weeks in most patients, associated with clearance of HBeAg. At end of follow-up, 81% of the treated patients had cleared HBeAg vs 33% of the control group (p less than 0.01). Changes in other HBV markers were more frequent in the treated patients, though insignificantly. The type of response to therapy was significantly related to the duration of illness, being shortest in those who cleared HBsAg. A complete response to therapy with loss of HBsAg was associated with marked reduction in biochemical and histological activity. A partial response with clearance of HBeAg was associated with moderate improvement in biochemical parameters and ongoing activity in liver histology; whereas persistence of HBeAg was associated with elevated aminotransferases and histological deterioration in most cases. The rise in aminotransferases during seroconversion was associated with hepatic decompensation and death on 3 occasions: one during spontaneous seroconversion, and the other 2 during IFN therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunologic and morphologic typing as prognostic factor in M1 acute myeloblastic leukemia.

Thirty-two patients diagnosed in the Gustave Roussy Hospital between 1981 and 1988 were divided into three groups according to the morphology of the predominant blast cells in the bone marrow. Cytochemical reaction in the form of Sudan Black, myeloperoxidase reaction and immunological typing were performed for 13 patients. Twelve patients were treated with protocol AML6, eight with protocol AML8, one with protocol LAL16, and the rest with other types of protocols. To a certain extent morphological maturation was correlated with antigenic differentiation. The lack of expression of Ia antigen (HLA-DR) identified patients with a low rate of relapse during the first year of remission, and patients with My7 positive leukemia had a worse prognosis than did patients with My7 negative leukemia. The 2 patients positive for MO1 antigen did not achieve remission, and out of 9 patients who were negative for MO1 antigen only 2 achieved remission for approximately 1 year. Only 1 of 3 patients with biphenotypic leukemia achieved remission for more than 1 year.

Experience with ofloxacin in enteric fever.

Ofloxacin 200 mg b.i.d. for 8 days was employed in 28 patients with enteric fever with a positive blood culture. All patients were cured clinically and bacteriologically. The fever subsided within a mean of 3.1 days (range 1.6.5.3). No relapse, clinical or bacteriological, was observed when patients were followed up for 12 weeks.

Single-dose pharmacokinetics of aztreonam in healthy volunteers and renal failure patients.

The pharmacokinetics of aztreonam were studied in 6 healthy male volunteers and 12 male patients with various degrees of chronic renal failure after intravenous bolus injection of 1g of the drug. Serum pharmacokinetics of aztreonam were described by an open, two-compartment kinetic model. The serum levels of aztreonam exceeded the reported minimum inhibitory concentration (MIC)90 for Enterobacteriaceae for 8 hours and up to 24 hours, in healthy volunteers and renal failure patients, respectively. However, the serum levels of the drug exceeded the MIC50 for Pseudomonas aeruginosa for only 4 hours and 12 hours in healthy volunteers and patients, respectively. The half-life of elimination (t 1/2/beta) increased significantly (P less than 0.001) from 1.8 +/- 0.14 h in healthy volunteers and to 4.9 +/- 1.1 h in patients with renal failure. The total serum clearance of aztreonam decreased significantly (P less than 0.001) from 84.2 +/- 7.8 ml/h/kg in healthy volunteers to 30.2 + 9.2 ml/h/kg in patients with renal failure. A linear correlation (r = 0.971, P less than 0.001) was found between creatinine clearance and the total serum clearance of aztreonam. The AUC0-infinity increased significantly (P less than 0.001) from 137.5 +/- 12.2 micrograms/h/ml in healthy volunteers to 464 +/- 114.5 micrograms/h/ml in patients with renal failure.

The prognostic implications of an immunological classification of acute lymphoblastic leukemia.

Thirty-one patients with newly diagnosed acute lymphoblastic leukemia were examined before receiving any treatment and their clinical and laboratory data were analyzed in order to determine the possible correlation between clinical presentation, morphologic sub-classes, cytochemical reactions, immunological phenotypes and cytogenetic findings. Each of the previous parameters and response to therapy were also examined for correlation. The analysis of clinical and laboratory characteristics of patients according to their immunological phenotype did not show any significant male sex bias, age distribution, hepatomegaly or splenomegaly at diagnosis. The analysis of clinical response of patients did not demonstrate any significant influence of sex, age, initial WBC count or the presence of a big tumor mass at diagnosis. There were no significant differences between our two major immunological subclasses Non-T CALLA+ ALL, and Pre-T ALL regarding proportions of patients in continuous remission, and relapse-free survival durations. The analysis of clinical and laboratory characteristics of patients on the basis of their chromosome categories did not show any significant sex bias, age distribution, initial WBC count, tumoral presentation or morphological subtypes at diagnosis, although there was an apparent male predominance in the pseudodiploid category and female predominance in the hyperdiploid category. Our results concerning the prognostic implication of CALLA were contradictory to those of several other investigators.

Re-evaluation of the value of ascitic fluid pH lactate dehydrogenase and total proteins in the diagnosis of spontaneous bacterial peritonitis (SBP).

In view of high mortality, variable clinical presentation, and late results of bacterial culture, early diagnosis of SBP and treatment are based on indirect parameters of infection. Forty-two patients with ascites and liver cirrhosis were studied. Ascitic fluid (AF) was examined for total protein content, pH, lactate dehydrogenase, amylase, absolute polymorphonuclear cell count (PMN) and for presence of bacteria by examining a fresh smear of the deposit and culture of the fluid under aerobic and anaerobic conditions. AF/serum gradient of total proteins and LDH was calculated. One patient proved to have a malignant ascites and was excluded. The remaining 41 patients fell into two groups: Group I PMN less than 250 cell mm-3, culture negative, sterile ascites, 36 patients. Group II PMN greater than 250 cell mm-3. (a) Culture positive neutrophilic ascites (SBP), three patients. (b) Culture negative neutrophilic ascites (CNNA), two patients. In both CNNA and SBP:AF/serum total LDH gradient greater than 0.75 In the sterile group: AF/serum total LDH gradient less than 0.58 There was no correlation between presence of infection and ascitic fluid pH, protein content and AF/serum total protein gradient. Therefore AF PMN greater than 250 mm and AF/serum total LDH gradient greater than 0.6 should be considered reliable, indirect parameters of infection, and CNNA a variant of SBP with a small bacterial inoculum size.

The pattern of antimicrobial use in general hospitals in Egypt.

This work was carried out to study the pattern of use of antimicrobial agents in Egypt. 2034 files were selected from two general hospitals by a systematic random sampling method, and the data concerning the antimicrobials were collected from each file. The results of this study showed that there was misuse of these agents both in therapy and prophylaxis. Antibiotics were prescribed to 80.17% of admitted patients. In most of the cases they were prescribed without documented proof of infection and were prescribed for conditions in which antimicrobial use is not justified for either therapy or prophylaxis. Among patients who received antibiotics, 30.8% received repeated courses, in most of whom there was no reasonable indication.

Experience with antimicrobial combinations in urinary tract infections.

Four antimicrobial combinations were tried in the management of recurrent upper urinary tract infections: (i) rifampicin + trimethoprim (50 patients); (ii) amoxycillin + clavulanic acid (50 patients); (iii) ampicillin + sulbactam (10 patients); and (iv) pivampicillin + pivmecillinam (50 patients). The initial and final microbiological success rate was excellent with all four drug combinations; all were well tolerated. Although monotherapy should be the rule in antimicrobial chemotherapy, there are certain indications that may necessitate combination therapy; for example, to cover a wider spectrum of activity with mixed infections or before the causative pathogen is isolated and its antimicrobial sensitivity defined, to delay the emergence and to avoid selection of resistant strains, to convert a bacteriostatic into a bactericidal effect and to obtain a synergistic (or at least an additive) antimicrobial effect by the combination.

CNS prophylaxis using a triple intrathecal drug therapy without cranial irradiation in acute lymphoblastic leukaemia.

After remission-induction chemotherapy in 31 patients with acute lymphoblastic leukaemia, patients immediately received CNS prophylaxis. Thirteen patients received triple intrathecal drug therapy, while 18 patients received intrathecal methotrexate and cranial irradiation; systematic chemotherapy was administered as well to both groups. Six patients developed CNS leukaemia during complete remission, 2 in the non-radiated patients and 4 in patients who had received cranial irradiation. Drug chemoprophylaxis may therefore substitute cranial radiotherapy when effective systemic regimens are used. Such CNS chemoprophylaxis will result in fewer, long-term CNS side-effects.