Immunologic assessment during treatment of rheumatoid arthritis with anti-CD5 immunoconjugate.

OBJECTIVE: To determine if sustained immunologic effects occurred after treatment of patients with rheumatoid arthritis (RA) with an immunoconjugate of murine anti-CD5 monoclonal antibody with ricin A chain (anti-CD5). METHODS: We measured lymphocyte populations, mitogen induced peripheral blood mononuclear cell (PBMC) stimulation, cytokine levels, immunoglobulin levels, in vivo immune function, and clinical outcomes in 9 patients with RA treated with anti-CD5. RESULTS: The treatment of patients with RA with anti-CD5 was associated with marked acute depletion of peripheral blood lymphocytes (p < 0.01) during and immediately after treatment. A sustained decrease in the number of CD3, CD4, CD5, and CD8 bearing lymphocytes persisted for 2 months after treatment (p < 0.05). After 3 months a mild decrease in the number of these lymphocyte populations persisted, but when compared to baseline values, the differences were not found to be statistically significant. Phytohemagglutinin induced PBMC proliferation was decreased at the 3-month followup (p < 0.05). Evaluations of mitogen induced cytokine and immunoglobulin production, immunoglobulin level, autoantibody, and in vivo antibody response to tetanus toxoid did not show any consistent change from baseline. CONCLUSION: Anti-CD5 treatment of RA appears to be associated with a decrease in the population of cells bearing CD5, but does not appear to induce any persistent immunologic abnormalities.

Compatibility and stability of cefazolin sodium, clindamycin phosphate, and gentamicin sulfate in two intravenous solutions.

We studied the compatibility and stability of clindamycin phosphate admixed with gentamicin sulfate and cefazolin sodium in small-volume diluents under specific storage conditions. In two replicate 100 ml dilutions of NaCl 0.9% injection and dextrose 5% (D5W) injection, clindamycin phosphate 900 mg was admixed with gentamicin sulfate 80 mg and cefazolin sodium 1 g. Drug concentrations were determined at the time of preparation and at 1, 4, 8, 12, 24, and 48 hours. Clindamycin and cefazolin were assayed by high-performance liquid chromatography and gentamicin was assayed by fluorescence polarization immunoassay. Visual inspections and pH determinations of each solution were performed at each assay time. Test solutions were maintained at constant room temperature and fluorescent lighting. Concentrations of clindamycin and gentamicin remained greater than 90 percent of the original concentrations throughout the study. Cefazolin concentrations dropped below 90 percent in D5W injection at 4 hours after admixture and at 12 hours after admixture in NaCl 0.9% injection. Visual analyses and pH changes revealed no significant changes. The combination of clindamycin phosphate 900 mg, gentamicin sulfate 80 mg, and cefazolin sodium 1 g in D5W 100 ml was found to be compatible for up to 4 hours. The duration of compatibility for these three drugs in 100 ml of NaCl 0.9% was 12 hours.

In vitro inactivation of aminoglycosides by cephalosporin antibiotics.

The in vitro inactivation of aminoglycoside antibiotics by semisynthetic penicillins complicates antibiotic assays. Due to the increasing number of new cephalosporins and use of aminoglycoside-cephalosporin combinations, we determined the in vitro stability of 28 aminoglycoside-cephalosporin combinations (gentamicin sulfate, tobramycin sulfate, netilmicin sulfate [10 micrograms/mL], and amikacin [20 micrograms/mL] in combination with cefazolin sodium, cefoxitin sodium, cefoperazone sodium, cefotaxime sodium, ceftazidime acid pentahydrate, cefsulodin sodium, or cefpiramide sodium at 100, 200, and 300 micrograms/mL). These mixtures were incubated at 37 degrees C and sampled at 0, 8, and 24 hours. Amikacin and tobramycin were most stable and netilmicin was the least stable of the aminoglycosides. Cefoxitin, ceftazidime, and cefotaxime were the least inactivating of the cephalosporins. When combined with first- and second-generation cephalosporins, aminoglycosides are relatively stable, but some laboratory precautions may be necessary when determining aminoglycoside levels in the presence of third-generation cephalosporin compounds.

Pharmacokinetics of cefoperazone (2.0 g) and sulbactam (1.0 g) coadministered to subjects with normal renal function, patients with decreased renal function, and patients with end-stage renal disease on hemodialysis.

The single-dose pharmacokinetics of intravenously administered cefoperazone (2.0 g) and sulbactam (1.0 g) were studied in normal subjects and in patients with various degrees of renal failure. In an open, parallel experimental design, six normal subjects (creatinine clearance, greater than 90 ml/min), two patients with mild renal failure (creatinine clearance, 31 to 60 ml/min), eight patients with moderate renal failure (creatinine clearance, 7 to 30 ml/min), and four functionally anephric patients (creatinine clearance, less than 7 ml/min) were studied. The functionally anephric patients were given two test doses to allow study of drug disposition both on and off hemodialysis. Serial blood and urine samples were collected from time zero to 12 h after dosing in normal subjects and from 0 to 72 h in renal patients. Serum concentrations of both drugs declined biexponentially. For cefoperazone, the terminal elimination half-lives averaged from 1.6 to 3.0 h and were similar in subjects and patients. No cefoperazone pharmacokinetic parameters were appreciably altered by renal failure or hemodialysis, and there was no correlation between the total body clearance of cefoperazone and estimated creatinine clearance. In contrast, the sulbactam total body clearance was highly correlated with estimated creatinine clearance (r = 0.92, P less than 0.01) and was significantly higher in normal volunteers than in the renally impaired groups (P less than 0.01). The sulbactam terminal elimination half-life in functionally anephric patients (9.7 +/- 5.3 h) differed significantly from that of normal volunteers (1.0 +/- 0.2 h) and patients with mild renal failure (1.7 +/- 0.7 h, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Compatibility of clindamycin phosphate with aztreonam in polypropylene syringes and with cefoperazone sodium, cefonicid sodium, and cefuroxime sodium in partial-fill glass bottles.

The stability and compatibility of clindamycin phosphate admixed with four beta-lactams, an experimental monobactam (aztreonam), and three cephalosporins (cefoperazone sodium, cefonicid sodium, and cefuroxime sodium), were studied. Aztreonam alone and the combination of clindamycin phosphate-aztreonam were prepared in duplicate polypropylene syringes. Each cephalosporin antibiotic as well as the three clindamycin phosphate-cephalosporin combinations were admixed in duplicate 100 ml partial-fill glass bottles containing either dextrose 5% in water or NaCl 0.9%. All solutions were examined, antibiotic concentrations were determined, and pH was measured at the time of admixture and 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under fluorescent lighting for the length of the study. Antibiotic concentrations were determined by drug-specific high performance liquid chromatographic assays. Significant instability or incompatibility was defined as a decrease in concentration of greater than ten percent relative to the initial concentration measured at the time of admixture. All antibiotics were stable for 48 hours. In the combination studies, clindamycin was stable for 48 hours, both in partial-fill glass bottles and syringes. Aztreonam, cefoperazone, cefonicid, and cefuroxime were also stable for 48 hours.

Compatibility and stability of clindamycin phosphate-aminoglycoside combinations within polypropylene syringes.

The stability and compatibility of clindamycin phosphate admixed separately with gentamicin sulfate, tobramycin sulfate, and amikacin sulfate in polypropylene syringes under specific storage conditions were studied. In duplicate syringes, clindamycin phosphate 900 mg was admixed with sterile NaCl 0.9% l ml and with either gentamicin sulfate 120 mg, tobramycin sulfate 120 mg, or amikacin sulfate 750 mg. In duplicate polypropylene syringes, control solutions of clindamycin phosphate and each aminoglycoside were prepared separately and stored under the same conditions. The clindamycin control consisted of clindamycin phosphate 900 mg in 6 ml. The gentamicin and tobramycin controls consisted of gentamicin sulfate and tobramycin sulfate 120 mg in 3 ml plus 1 ml of sterile NaCl 0.9%. The amikacin control consisted of amikacin sulfate 750 mg in 3 ml plus 1 ml of sterile NaCl 0.9%. Drug concentrations were determined at the time of preparation and 1, 4, 8, 12, 24, and 48 hours thereafter. Aminoglycosides were assayed by fluorescence polarization immunoassay and clindamycin was assayed by high performance liquid chromatography. Visual inspections and pH determinations of each combination and control solution were performed at each assay time. For the clindamycin, gentamicin, tobramycin, and amikacin control solutions, changes in concentration were within ten percent of the original concentration. Concentrations of clindamycin and gentamicin when admixed together also remained within ten percent of the original concentration. Similar results were found with concentrations of clindamycin and amikacin when admixed together. Tobramycin and clindamycin formed a lasting precipitate upon initial contact when admixed under the study conditions.

Compatibility of clindamycin phosphate with amikacin sulfate at room temperature and with gentamicin sulfate and tobramycin sulfate under frozen conditions.

The stability and compatibility of clindamycin phosphate with three aminoglycosides, amikacin sulfate, tobramycin sulfate, and gentamicin sulfate, admixed in either glass bottles or plastic bags, were studied under various storage conditions. In addition to the various two-drug combinations, each antibiotic was studied alone in the same solutions under the same storage conditions investigated for the various combinations. Clindamycin phosphate was admixed with amikacin sulfate in 100 ml glass bottles of both dextrose 5% in water (D5W) and NaCl 0.9%. The resultant solutions were examined for visual clarity; both pH and antibiotic concentrations were measured at the time of mixing and at 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under ambient lighting conditions throughout the observation period. Clindamycin phosphate was also admixed with tobramycin sulfate and gentamicin sulfate, in separate experiments, in 50 ml plastic bags of D5W and NaCl 0.9%. These solutions were examined, at the time of mixing, for visual clarity, pH, and antibiotic concentration and then frozen at -20 degrees C. They were thawed 14 and 28 days later and reexamined. Clindamycin phosphate concentrations were measured by high performance liquid chromatography; those of the aminoglycosides were determined by a fluorescence polarization immunoassay. A working definition of significant instability or incompatibility was defined as a greater than 10 percent loss of original antibiotic concentration. All single antibiotic solutions were stable throughout the observation periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability of clindamycin phosphate with aztreonam, ceftazidime sodium, ceftriaxone sodium, or piperacillin sodium in two intravenous solutions.

In admixtures containing clindamycin and either aztreonam, ceftazidime, ceftriaxone, or piperacillin in either 5% dextrose injection (D5W) or 0.9% sodium chloride injection (NS), the stability of each drug was studied. Each of the following combinations of drugs was added to 100-mL glass bottles of base solution: clindamycin phosphate 0.9 g and aztreonam 2.0 g, clindamycin phosphate 0.9 g and ceftazidime sodium 2.0 g, clindamycin phosphate 1.2 g and ceftriaxone sodium 2.0 g, and clindamycin phosphate 0.9 g and piperacillin sodium 4.0 g. Duplicate samples were prepared. Admixtures containing each single drug were also tested. Samples were visually inspected and tested for pH and drug concentration immediately after mixing and at 1, 4, 8, 12, 24, and 48 hours of storage in room temperature and light. Drug concentrations were determined by high-performance liquid chromatographic assay methods. Ceftriaxone retained greater than 90% of its original concentration for 24 hours in single-drug admixtures in NS, for eight hours with clindamycin in NS, and for one hour with clindamycin in D5W. Ceftazidime retained greater than 90% potency for 24 hours with clindamycin in D5W. In all other test admixtures, all drugs were stable for 48 hours. Under the conditions studied, clindamycin is compatible in the admixtures tested with aztreonam and piperacillin. Admixtures of clindamycin and ceftazidime in D5W should be used within 24 hours at room temperature. Clindamycin and ceftriaxone can be mixed in NS if administered within eight hours, but ceftriaxone is stable for only one hour in combination with clindamycin in D5W.

Norfloxacin: a quinoline antibiotic.

Norfloxacin is a quinoline (quinolinecarboxylic acid) that should prove successful in treating infections that currently require hospitalization and intravenous antibiotics. Although a nalidixic acid derivative, it possesses greater antibacterial activity against gram-positive and gram-negative bacteria. Compared with other antimicrobial agents, norfloxacin is more potent than the aminoglycosides, first-, second-, and third-generation cephalosporins, tetracycline, trimethoprim-sulfamethoxazole, carbenicillin, piperacillin, nalidixic acid, oxolinic acid, cinoxacin, and enoxacin. In the clinical studies to date, the side effects of norfloxacin have been minimal, but include nausea, vomiting, anorexia, dizziness, headache, drowsiness, depression, and a bitter taste in the mouth. In studies with more than 4000 patients, the incidence of side effects ranged from 3.9 to 4.7 percent, with most appearing by the second day of therapy.

Clinical risk factors for prolonged PT/PTT in abdominal sepsis patients treated with moxalactam or tobramycin plus clindamycin.

Factors associated with prolongation of the prothrombin time were analyzed in 94 patients with intra-abdominal sepsis. Patients were randomized prospectively to receive either the combination of tobramycin and clindamycin (TM/C) or moxalactam (MOX). This paper presents a retrospective review designed to compare the frequency of prolonged clotting times and to analyze predisposing factors. Prothrombin time (PT) prolongation occurred more frequently in patients given moxalactam (19 of 47 patients) than in patients given the combination of tobramycin and clindamycin (9 of 47 patients) (p less than 0.05). Prolongation of the partial thromboplastin time (PTT) occurred in all patients with a prolonged PT. Liver disease, upper gastrointestinal surgery, and use of cimetidine were more frequent in those patients with abnormal PT/PTT values (p less than 0.05). Two moxalactam-treated patients with subsequent PT/PTT prolongation had individual clotting factors assayed before moxalactam treatment and at the time of detection of the abnormal PT. The activity of clotting factors II, VII, VIII, IX, X, and XII was reduced during MOX therapy. Treatment with vitamin K reversed the abnormality. In view of underlying abnormalities and rapid response to parenteral vitamin K, the mechanism is probably an acute vitamin K deficiency superimposed upon chronic vitamin K deficiency. In patients with intra-abdominal infection, those treated with MOX are more likely to develop abnormal PT than those treated with TM/C. Since abnormal PT/PTT was common even in TM/C patients, supplemental vitamin K should be considered for all seriously ill, older patients with abdominal infections.