Does Surgical-site Multimodal Drug Injection After Palmar Plating of Distal Radius Fractures Improve Pain Scores?

BACKGROUND: Although palmar locked plating is a stable fixation method frequently used to treat unstable distal radius fractures (DRFs), surgical treatment may be painful, and so interventions to decrease that pain might improve our patients' experiences with surgery. Some surgeons use local multimodal drug injections to decrease postoperative pain after lower-extremity arthroplasty, but little is known about the effectiveness of a local multimodal drug injection in patients who undergo palmar plating for DRFs. QUESTIONS/PURPOSES: (1) Do patients who receive a local multimodal drug injection after palmar plating for unstable DRFs have better pain scores at 4, 8, 24, and 48 hours after surgery than patients who have not received such an injection? (2) Do patients who receive a local multimodal drug injection have lower fentanyl consumption and administration of anti-emetic drugs within the first 48 hours after surgery than patients who have not received such an injection? METHODS: A randomized controlled study was performed between August 2018 and August 2019 at a single tertiary care referral center. Patients who underwent palmar plating for DRFs under general anesthesia were eligible for inclusion. Patients were allocated into two groups: Those who received a local multimodal drug injection, and those who did not receive an injection. During the study period, 101 patients treated with palmar plating for DRFs met the inclusion criteria and were enrolled and randomized. Fifty-two patients were allocated to the multimodal injection group and 49 were allocated to the control group. Three patients (two in the multimodal injection group and one in the control group) were excluded after randomization because their pain level was not registered at any timepoint and so they could not be analyzed; our analysis was by intention to treat, and there was no crossover. After palmar plating, patients in the multimodal injection group received an injection of ropivacaine (10 mL), morphine (5 mL), ceftezole (5 mL) as well as normal saline (5 mL) to the periosteal area, pronator quadratus muscle, subcutaneous area, and skin. There were no differences between the groups in terms of age (62 years ± 13 years in the multimodal injection group versus 62 years ± 11 years in the control group; p = 0.93), gender (84% [42 of 50] women in the multimodal injection group versus 77% [37 of 48] women in the control group; p = 0.39), hand dominance (70% [35 of 50] dominant wrist in the multimodal injection group versus 60% [29 of 48] dominant wrist in the control group; p = 0.32) and AO/Orthopaedic Trauma Association (AO/OTA) classification (p = 0.57). All patients underwent treatment with the same perioperative protocol, and 25 µg of fentanyl was injected intravenously when a patient complained of pain and asked for additional pain control after surgery. In addition, when a patient complained of nausea or vomiting associated with fentanyl use, an anti-emetic drug was also injected. All nursing staff who administered the analgesics and anti-emetic drugs were blinded to treatment allocation. These two groups were compared regarding their pain level using a 100-mm VAS at 4, 8, 24, and 48 hours postoperatively. The minimum clinically important difference (MCID) for the VAS score was set to 20 mm. VAS scores were also collected by nursing staff who remained blinded to the treatment allocation. The total amount of fentanyl use and the number of patients who received anti-emetic drugs associated with administration of fentanyl within the first 48 hours were also recorded. RESULTS: With an MCID of 20 points, we found no clinically important reduction in VAS scores among patients who received a local multimodal injection compared with those who did not receive an injection at 4 hours (34 ± 15 versus 41 ± 20, mean difference -7.079 [95% CI -13.986 to -0.173]; p = 0.045), 8 hours (27 ± 16 versus 40 ± 19, mean difference -12.263 [95% CI -19.174 to -5.353]; p = 0.001), 24 hours (18 ± 12 versus 29 ± 20, mean difference -11.042 [95% CI -17.664 to -4.419]; p = 0.001), and 48 hours (9 ± 8 versus 10 ± 6, mean difference -1.318 [95% CI -4.000 to 1.365]; p = 0.33). Within the first 48 hours after surgery, fentanyl consumption was lower in patients receiving a local multimodal injection than in control patients (25 µg [range 0-100 µg] versus 37.5 µg [range 0-125 µg], difference of medians -12.5; p = 0.01). There was also a difference between the study groups in terms of the proportion of patients who received anti-emetic medications (16% [8 of 50] in the multimodal injection group versus 35% [17 of 48] in the control group, odds ratio = 2.879 [95% CI 1.102 to 7.519]; p = 0.03). CONCLUSIONS: Our data suggest that patients who received a surgical-site multimodal analgesic injection after palmar plating for a distal radius fracture had no clinically important reduction in pain scores, but they did consume lower doses of opioid analgesics and fewer of these patients received anti-emetic drugs within 2 days of surgery. The high-potency opioids or other analgesia usually used for postoperative pain management have many side effects. Thus, reducing additional analgesia is as important as postoperative pain management and a surgical-site multimodal analgesic injection is one of the methods to achieve this a goal. LEVEL OF EVIDENCE: Level I, therapeutic study.

Amoxicillin and clavulanate potassium in treating children with suppurative tonsillitis.

To evaluate clinical effects of amoxicillin and clavulanate potassium in the treatment of children with suppurative tonsillitis, 146 children with suppurative tonsillitis were randomly divided into a ceftezole sodium group and an amoxicillin and clavulanate potassium group. The two groups were given anti-infection treatment using different drugs. Symptomatic treatment was carried out once symptoms such as fever appeared. Five to seven days were taken as one treatment course. Blood routine examination and the detection of C-reactive protein (CRP) were performed three days after treatment. Indexes such as the time to the relief of symptoms, the count of white blood cells, the proportion of neutrophil and CRP levels and the incidence of adverse reactions were compared between groups to evaluate the curative effect. The overall response rate of the amoxicillin and clavulanate potassium group was 94.52%, while that of the ceftezole sodium group was 78.08%; the difference was statistically significant (P<0.05). The improvement of white blood cells and CRP levels of the amoxicillin and clavulanate potassium group was more obvious than that of the ceftezole sodium group (P<0.05). The difference of the time to the improvement of symptoms between the two groups had statistical significance; the amoxicillin and clavulanate potassium group was superior to the ceftezole sodium group (P<0.05). No severe drug-related adverse reactions were observed. Amoxicillin and clavulanate potassium dispersible tablet is effective in treating children with suppurative tonsillitis as it can rapidly relieve the clinical symptoms without increasing incidence of adverse reactions.

A Pharmacokinetic and Pharmacodynamic Study on Intravenous Cefazedone Sodium in Patients with Community-acquired Pneumonia.

BACKGROUND: As a time-dependent antibiotic, the time of cefazedone concentration exceeds the minimum inhibitory concentration (MIC) is the key pharmacokinetic-pharmacodynamic (PK-PD) variable associated with the killing of pathogens. The purpose of the study was to evaluate the clinical regimen rationality of intravenous cefazedone sodium in the treatment of community-acquired pneumonia (CAP) by PK/PD study. METHODS: Ten patients with mild to moderate CAP were enrolled to receive intravenous cefazedone sodium (2 g q12 h) for 7-14 days. Blood samples were collected in any day during day 5-7. Sputum specimens were collected before treatment for bacteria isolated, and susceptibility to cefazedone determined. PK-PD analysis was performed using the noncompartmental analysis of Phoenix WinNolin software (version 6.1, Pharsight Corporation, CA, USA). The maximal time above MIC (ƒT > MIC) was calculated, and its correlation with clinical efficacy was analyzed. RESULTS: All 10 patients completed the study and 8 of them were cured. Six strains were isolated from patients before treatment (one for each patient) and all susceptible to cefazedone. Five patients of six in culture positive group were cured. All pathogens were cleared at the end of therapy. The MICs were between 0.25 and 1 mg/L. The main PK parameters were C max 175.22 ± 36.28 mg/L; T½ 1.52 ± 0.23 h; AUC (0-∞) 280.51 ± 68.17 mg·L -1·h -1 ; CL 7.37 ± 1.84 L/h; Vd 16.06 ± 4.42 L. The average ƒT > MIC was 55.45 ± 8.12%. CONCLUSIONS: Intravenous injection of cefazodone sodium with 2 g q12 h dosage regimen is used in the treatment of CAP caused by sensitive bacteria, either ƒT > MIC or clinical efficacy shows that such dosing regimen is reasonable.

Comparative evaluation of the tolerability of cefazolin and nafcillin for treatment of methicillin-susceptible Staphylococcus aureus infections in the outpatient setting.

BACKGROUND: Nafcillin and cefazolin are considered first-line therapy for most infections with methicillin-susceptible Staphylococcus aureus (MSSA), and recent studies have suggested similar clinical efficacy. Limited data are available on the comparative tolerability of these agents. METHODS: In this retrospective cohort analysis of patients treated with either nafcillin or cefazolin for MSSA infection in the outpatient parenteral antimicrobial therapy clinic at Massachusetts General Hospital from 2007 to 2011, the frequency of premature antimicrobial discontinuation (PAD) and drug-emergent events (DEEs) was calculated. RESULTS: Three hundred sixty-six and 119 patients were treated with nafcillin or cefazolin, respectively. The median anticipated duration of therapy was comparable at 28 (interquartile range [IQR], 16-37) and 29 (IQR, 24-39) days, respectively, for those treated with nafcillin and cefazolin. Fewer patients completed the prespecified treatment course with nafcillin than with cefazolin (PAD rate, 33.8% vs 6.7%; P < .0001). The hazard ratio for PAD in the nafcillin vs cefazolin groups was 2.81 (95% confidence interval [CI], 1.26-3.68). More patients in the nafcillin group developed rash (13.9% vs 4.2%; P = .002), renal dysfunction (11.4% vs 3.3%; P = .006), and liver function abnormalities (8.1% vs 1.6%; P = .01). Overall rates of DEEs per 1000 patient-days were 16.9 (95% CI, 10.4-27.3) and 4.8 (95% CI, 1.1-10.2), respectively. In 9 cases of nafcillin discontinuation, treatment was changed to cefazolin; all 9 completed treatment with no further observed DEEs. CONCLUSIONS: Nafcillin treatment was associated with higher rates of both PAD as well as DEEs compared with cefazolin treatment. This difference in tolerability, in addition to efficacy and cost, should be considered when decisions for outpatient parenteral MSSA treatment are made.

Investigation of the toxic functional group of cephalosporins by zebrafish embryo toxicity test.

2-mercapto-5-methyl-1,3,4-thiadiazole (MMTD) is the 3'-side chain of cephalosporin including cefazolin sodium (CFZL) and cefazedone (CFZD). It is not only present in finished products as the residual precursor, but also produced through drug degradation. Performing the zebrafish embryo toxicity test, we evaluated the toxicity effects of cefazolin sodium, cefazedone, their synthetic precursors and intermediates. Our results suggest that the teratogenic effect of cefazedone and cefazolin sodium on zebrafish embryonic development is associated with the structure of MMTD. They mainly interfere with the development of tissues and organs derived from embryonic ectoderm and mesoderm. We further consider the rationality of the quality control limit of MMTD (1.0%) in the specification. As the acceptable daily intakes (ADIs) of cefazolin is 10 µg/kg per day 16 and the minimum teratogenic concentration of MMTD is tenfold lower than that of cefazolin sodium, we recommend that the acceptable daily intakes of MMTD should be 1 µg/(kg day). In general, the therapeutic dose of cefazolin sodium is 2-4 g/day. Based upon the calculation of MMTD quality control limits (1.0%), MMTD intake can be 20-40 mg/day, which will be much more than the acceptable daily intake value of 1 µg/(kg day). Thus, MMTD should be recommended as a specified impurity and qualified as serious again.

Determination of cefazedone in human plasma by high performance liquid chromatography-tandem mass spectrometry: Application to a pharmacokinetic study on Chinese volunteers.

A rapid, sensitive and simple high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for determination of cefazedone in human plasma using metronidazole as internal standard (IS). The chromatographic separation was achieved on an Ultimate XB-CN column (2.1mm×150mm, 5µm) with an isocratic mobile phase of acetonitrile and 20mM ammonium acetate in 0.1% formic acid in water (15:85, v/v). Detection was performed using electrospray ionization in positive ion multiple reaction-monitoring mode (SRM), monitoring the transitions m/z 548.2→344.1 for cefazedone and m/z 172.2→128.1 for IS. Calibration curves were linear over a wide range of 0.20-401.12µg/mL for cefazedone in plasma. The lower limit of quantification (LLOQ) was 0.20µg/mL. The intra- and inter-day precisions were less than 7.2%. The average recovery of cefazedone was 90.8-91.0%. The validated method was successfully applied to the pharmacokinetic study of cefazedone in Chinese healthy volunteers following intravenous (IV) administration of 500, 1000 and 2000mg cefazedone injection.

[Approach to the crystalline characteristics of ceftezole sodium].

AIM: To study the crystalline characteristics of ceftezole sodium. METHODS: Ceftezole sodium crystals were obtained from different solvents. X-ray diffraction, DSC, TGA, etc were used to analyze the crytals. RESULTS: Ceftezole sodium crystal was easily obtained in isopropanol-water mixture. It consists of ceftizole sodium monohydrate, which consists of type I and type II two different crystal forms. Powder X-ray diffraction patterns showed differences between type I and the type II crystal forms. Peaks at 8 degrees and 18 degrees in diffractograms of the type I, but at 9 degrees and 18.6 degrees in the type II could be observed. Water molecules in different crystal forms had different combining condition. They lost during 35-117 degrees C in the type I form, but lost during 110-160 degrees C in the type II form. CONCLUSION: Structure of ceftizole sodium monohydrate crystal obtained in different circumstance could be some vary, which influence upon the thermal stability of the compound. The type I crystal form is more stable than the type II.

Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis.

BACKGROUND: Infection remains a serious complication after permanent pacemaker implantation. Antibiotic prophylaxis is frequently prescribed at the time of insertion to reduce its incidence, although results of well-designed, controlled studies are lacking. METHODS AND RESULTS: We performed a meta-analysis of all available randomized trials to evaluate the effectiveness of antibiotic prophylaxis to reduce infection rates after permanent pacemaker implantation. Reports of trials were identified through a Medline, Embase, Current Contents, and an extensive bibliography search. Trials that met the following criteria were included: (1) prospective, randomized, controlled, open or blind trials; (2) patients assigned to a systemic antibiotic group or a control group; (3) end point events related to any infection after pacemaker implantation: wound infection, septicemia, pocket abscess, purulent secretion, right infective endocarditis, inflammatory signs, a positive culture, septic pulmonary embolism, or repeat operation for an infective complication. Seven trials met the inclusion criteria. They included 2023 patients with established permanent pacemaker implantation (new implants or replacements). The incidence of end point events in control groups ranged from 0% to 12%. The meta-analysis suggested a consistent protective effect of antibiotic pretreatment (P=.0046; common odds ratio: 0.256, 95% confidence interval: 0.10 to 0.656). CONCLUSIONS: Results of the present meta-analysis suggest that systemic antibiotic prophylaxis significantly reduces the incidence of potentially serious infective complications after permanent pacemaker implantation. They support the use of prophylactic antibiotics at the time of pacemaker insertion to prevent short-term pocket infection, skin erosion or septicemia.

[Stability of various cephalosporins in solutions. Cefazolin, cefazedone, cefaclor]. / Ob ustoichivosti nekotorykh tsefalosporinov v rastvorakh. Tsefazolin, tsefazedon, tsefaklor.

The kinetics of splitting out the substitute at C3 in the molecule of beta-lactam antibiotics such as cefazolin, cefaclor, cefazedone and others as well as that of splitting out the chlorine atom in the side radical of the cefazedone molecule was studied within wide ranges of pH and temperature. The destruction processes for all the investigated compounds were shown to be described by the 1st order equations. The values of the activation energy, pre-exponential factors and reaction order by the hydrogen ions were measured. This provided the mathematical description of the destruction processes within wide ranges of pH and temperature. An unusual mechanism of synchronous splitting out the substitute at C3 and one of the chlorine atoms in the side radical of the cefazedone molecule was observed.

[Sequestered bone infection after Kirschner wire osteosynthesis of humeral head fracture]. / Sequestrierender Knocheninfekt nach Kirschnerdraht-Osteosynthese einer Oberarmkopffraktur.

Percutaneous stabilization of fractures of the humeral head by K-wires is a proved therapy. This proceeding provides enough stability for early moving of the joint and has a low incidence for complications. In the case described here the special is the cause for local infection: local osteonecrosis induced by drilling-holes too close together.

Immunotoxicity of cephalosporins in mice.

This study was performed in female B6C3F1 mice to confirm previously observed effects of selected cephalosporin antibiotics on nonspecific immunity, and to determine possible effects on specific acquired immunity and host resistance. Mice were treated intravenously with DQ-2556, ceftizoxime or ceftezole at 800 mg/kg/day for 3, 5, or 7 consecutive days. All three compounds increased total serum IgM levels from day 3, but had no effects on total serum IgG levels and the thymus weight. All three cephalosporin antibiotics caused a slight increase in spleen weight and splenic germinal centers were enlarged after 5- or 7-day treatments. Antibody responses to type III pneumococcal polysaccharide (S3), a T-cell-independent immunogen, and sheep red blood cells (SRBC), a T-cell-dependent immunogen, were slightly decreased after 5-day dosings with each compound, and reached significance in DQ-2556 (response to S3) and ceftizoxime (response to S3 and SRBC). None of the tested cephalosporin antibiotics altered delayed-type hypersensitivity to oxazolone or host resistance to Plasmodium yoelii, indicating that the antibiotic-treated mice retained the capacity to mount a multicomponent and sustained protective immune response. These data suggest that although cephalosporins may cause polyclonal expansion of B cells with associated increases in total serum IgM, they do not affect the tested measures of cell-mediated immunity or host resistance. The decreased IgM antibody responses to S3 and SRBC are associated with but not known to be causally related to the concurrent IgM hypergammaglobulinemia.

Antibacterial activity of cefcanel.

The minimum inhibitory concentration of cefcanel, a new oral cephalosporin, has been determined for 182 clinical isolates, of which 84 were from the family Enterobacteriaceae, 45 were from the genus Streptococcus, 18 were nonfermentative rods, 25 were Haemophilus influenzae and 10 were Branhamella catarrhalis. In general, cefcanel was more active than the other cephalosporins against the species Escherichia coli, Klebsiella aerogenes and Proteus mirabilis. Among the genus Streptococcus only the enterococci were resistant to cefcanel. H. influenzae and B. catarrhalis showed also a reasonable susceptibility towards cefcanel. Oxidative rods were highly resistant to cefcanel.

Determination of cefcanel in plasma and urine by high-performance liquid chromatography using coupled columns, after administration of the new cephalosporin prodrug cefcanel daloxate hydrochloride.

A rapid and sensitive high-performance liquid chromatographic method has been developed for the determination in plasma and urine of the new cephalosporin cefcanel. The method involves a simple deproteinizing step followed by separation on a coupled-column chromatographic system with ultraviolet detection. Limits of quantification were 0.2 microM for plasma samples and 2 microM for urine samples. The method has been used for the determination of cefcanel in various clinical studies.

In vitro activity of cefcanel versus other oral cephalosporins.

Cefcanel is a new orally absorbed cephalosporin. Its activity was compared with that of cefuroxime, cefaclor, cephalexin, and cefixime against gram-positive and negative aerobic and anaerobic bacteria. Cefcanel had excellent activity against methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis, MIC90 1 micrograms/ml, superior to the other oral cephalosporins. However, methicillin-resistant staphylococci were resistant, MIC greater than or equal to 16 micrograms/ml. Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.015-1 micrograms/ml, concentrations comparable to other cephalosporins. Clostridium spp. were inhibited by 0.25 micrograms/ml, 8- to 128-fold lower concentrations than were found for other agents, but the MICs were greater than 64 micrograms/ml for Bacteroides spp. The MIC90 for Moraxella catarrhalis was 1 micrograms/ml, similar to cefuroxime but 16-fold greater than the MICs of cefixime. Escherichia coli and Klebsiella pneumonia which were high beta-lactamase producers were resistant, MICs greater than 64 micrograms/ml, and 50% of Enterobacter cloacae and Citrobacter freundii were resistant. Cefcanel was hydrolyzed by TEM-1, TEM-3 and Moraxella Bro-1 beta-lactamases. Escherichia coli containing TEM-1, 2, 3, 5, 7, and 9 had cefcanel MICs of greater than or equal to 16 micrograms/ml. Although cefcanel inhibited gram-positive species as well as or at lower concentrations than other cephalosporins, it lacked activity against gram-negative species that produced common plasmid beta-lactamase although it inhibited Haemophilus influenzae carrying TEM-1.

[Use of preventive intra-operative antibiotic administration in appendectomy. A pharmacokinetic study]. / Nutzen der intraoperativen Antibiotikaprophylaxe bei Appendektomie. Eine pharmakokinetische Studie.

Studies on Cefazedone-kinetics in serum and subcutaneous fat tissue showed an early and lasting tissue concentration high above minimal inhibitation concentrations so that intraoperative single-shot administration of antibiotics are proven to be effective. Due to these pharmacokinetic patterns the results of an earlier prospective trial is confirmed that single-shot antibiotics during surgery are useful to reduce postoperative wound sepsis rate after appendectomy.

Efficacy of cefcanel on staphylocci.

The minimum inhibitory concentration (MIC) of cefcanel, a new oral cephalosporin, has been tested against 153 staphylococci subdivided into the species Staphylococcus aureus. S. epidermidis sensu lato and S. saprophyticus, with and without beta-lactamase production. The concentration inhibiting 50% of the strains was 0.5 mg/l for all three species while the corresponding values for 90% of the strains were 1, 2 and 1 mg/l, respectively. These values apply to all the strains. The MICs of the non-beta-lactamase-producing strains were identical to the MICs of the beta-lactamase-producing strains for S. aureus, three twofold steps lower for S. epidermidis and one step higher for S. saprophyticus. Consequently, beta-lactamase production had no consistent consequences for the activity of cefcanel against S. aureus and S. saprophyticus. In contrast, the beta-lactamase production of S. epidermidis did influence the activity of cefcanel. Among the tested cephalosporins, cefcanel had the highest antistaphylococcal activity, and no strain was resistant to this new cephalosporin.

Synthesis and mechanisms of decomposition of some cephalosporin prodrugs.

The delta-3 and delta-2 methyl esters of cefazolin were synthesized. The kinetics and mechanisms of degradation of the methyl esters and the delta-3 and delta-2 isomers of pivaloyloxymethyl prodrug esters of the new cephalosporin ceftetrame (Ro 19-5247) were investigated in buffer systems and in human plasma in vitro. The major hydrolytic products of all the delta-3 and delta-2 esters were the inactive delta-2 cephalosporin free acids. The following reaction scheme describes the in vitro hydrolysis of these compounds: [formula: see text]. In addition, there was evidence of opening of the beta-lactam ring to form cephalosporoic acid when the methyl ester of cefazolin was studied in human plasma and in the presence of penicillinase. For the methyl esters, the processes represented by k12, k21, and k20 were operative in buffers; in human plasma, the processes represented by k12, k21, and k20 were operative in addition to cephalosporoic acid formation. For the isomers of the cephalosporin prodrug ester Ro 19-5248 only k12 and k20 were operative in buffers; in human plasma all pathways were operative and there was no evidence of cephalosporoic acid formation. In all cases, the processes represented by k12, k21, and k20 were subject to general and/or specific base catalysis.

The postantibiotic effect of cefcanel on beta-hemolytic streptococci group A in vitro and in vivo.

The postantibiotic effect (PAE) of cefcanel, a new oral cephalosporin with high in vitro activity against Gram-positive bacteria, was investigated. Ten clinical isolates of Streptococcus pyogenes group A and one reference strain (M12, P1800) were exposed to 5 X MIC of cefcanel for 2 h in vitro. The PAE was found to be 2.3 (range 1.7-3.2) h. To investigate the PAE in vivo, a newly developed animal model with implanted tissue cages in rabbits was used. The rabbits received different doses of cefcanel i.v. and unbound concentrations in the tissue cage fluid (TCF) were measured. The protein binding of cefcanel in TCF was approximately 98%. Above a certain dose level, unexpectedly high TCF concentrations were found, indicating that the albumin binding capacity for the drug was surpassed. A PAE in vivo of 0.9-2.6 h was confirmed for cefcanel when the free drug concentration in TCF exceeded 3 X MIC.

Influences of cephem antibiotics on the immune response in mice.

The effects of six cephem antibiotics, including ceftezole, cefmetazole, cefoxitin, cefotiam, cefoperazone, and cefotaxime, on murine humoral immunity were examined. In female BDF1 mice each cephem antibiotic was administered at a dose of 800 mg/kg/day i.v. for 7 consecutive days. Among the antibiotics tested, only ceftezole and cefoperazone induced a significant increase in serum total IgM, but not in serum total IgG. Especially in case of ceftezole, the mice developed splenomegaly due to the proliferation of IgM-producing cells in the germinal centers. The proliferation of splenic IgM-producing cells was also observed in female thymus-deficient Balb/c-nu/nu mice receiving intravenous ceftezole. Thus, the drug was indicated to enhance the polyclonal IgM production in mice by acting as a B cell mitogen. This is consistent with the in vitro finding that ceftezole exhibited a mitogenic effect on whole spleen cells from BDF1 mice, but not on B cell depleted spleen cells.

In vitro activities of cefcanel and some other cephalosporins against Pasteurella multocida.

Thirty-five strains of Pasteurella multocida from humans and animals were tested for susceptibility to five cephalosporins by a broth dilution method. Cefcanel showed high activity against all isolates (MIC and MBC, less than or equal to 0.64 micrograms/ml). The corresponding figure for cefaclor and cefuroxime was 2.56 micrograms/ml. Cefadroxil and cephalexin were the least active compounds tested.