Pharmacokinetics and bioequivalence studies of cefteram pivoxil in healthy Chinese volunteers.

A simple, sensitive and specific method has been developed for the determination of cefteram in human plasma. Sample preparation was accomplished through protein precipitation with 20% trichloroacetic acid (v/v) and chromatographic separation was performed on a C18 column at 25 degrees C. The mobile phase consisted of methanol-aqueous 20 mM ammonium acetate (18:82, v/v) at flow rate of 1.0 mL/min. Wavelength was set at 235 nm. The lower limit of quantification was 0.04 microg/mL and the assay exhibited a linear range of 0.04-3.2 microg/mL (r=0.9996). The relative recoveries of cefteram from human plasma at three different concentrations were more than 90%. The method was successfully applied to investigate the bioequivalence between two kinds of cefteram pivoxil preparations (test vs reference) in 24 healthy Chinese volunteers. After a single 100 mg dose for the test and reference product, the resulting means of major pharmacokinetic parameters such as AUC(0-t), AUC(0-infinity), Cmax and Tmax of cefteram pivoxil were 4.75 +/- 1.35 vs 4.76 +/- 1.29 microg h/mL, 4.89 +/- 1.36 vs 4.91 +/- 1.29 microg h/mL, 1.65 +/- 0.45 vs 1.73 +/- 0.45 microg/mL and 1.48 +/- 0.59 vs 1.73 +/- 0.45 h, respectively, indicating that these two kinds of preparations were bioequivalent.

Pharmacokinetic and bioequivalence comparison of a single 100-mg dose of cefteram pivoxil powder suspension and tablet formulations: a randomized-sequence, open-label, two-period crossover study in healthy Chinese adult male volunteers.

BACKGROUND: Cefteram pivoxil (CFTM-PI) is an oral antibiotic available in powder suspension and tablet formulations indicated in China for the treatment of bacterial infections. Although these 2 formulations are marketed in China, published information regarding their pharmacokinetics and bioequivalence in the Chinese population is not available. OBJECTIVE: The aim of this study was to compare the pharmacokinetics and bioequivalence of the powder suspension (test) and tablet (reference) formulations of CFTM-PI 100 mg available in China. METHODS: This single-dose, randomized-sequence, open-label, 2-period crossover study was performed at the Nanjing First Hospital of Nanjing Medical University. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 100-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Plasma was assayed using a high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to 6 hours (AUC(0-6)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were obtained at intervals over the 6-hour period after study drug administration. The formulations were considered bioequivalent if the log-transformed ratios of C(max) and AUC were within the predetermined equivalence range (80%-125%) as established by the US Food and Drug Administration (FDA). Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events (AEs). RESULTS: Twenty-four Chinese male subjects (mean [range] age,24.2 [23-32] years;weight,64.3 [58-67] kg; height, 172 [167-185] cm) enrolled; all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-6;), and AUC(0-infinity) were 96.5 to 120.1, 95.7 to 110.2, and 96.2 to 110.4, respectively (all, P>0.05). Similar results were found for the data without log-transformation. No AEs occurred or were reported during the study. CONCLUSIONS: In this small study in healthy Chinese adult male volunteers, a single 100-mg dose of the powder-suspension formulation was bioequivalent to a single 100-mg dose of the tablet formulation based on the US FDA's regulatory definition (rate and extent of absorption). Both formulations were well tolerated.

[Antibiotic ophthalmic solutions evaluated by pharmacokinetic parameters of maximum concentration in the aqueous].

PURPOSE: In order to determine whether the one-component method for calculating drug concentration in the aqueous(AQCmax) is useful for selecting an appropriate ophthalmic solution, 6 general purpose antimicrobial ophthalmic solutions already on the market were investigated. METHODS: The drugs examined were levofloxacin (LVFX), chloramphenicol(CP), erythromycin lactobionate(EM), micronomicin sulfate(MCR), cefmenoxime hydrochloride(CMX) and disodium sufobenzyl penicillin(SBPC). Fifty microliters of each solutions was instilled into the cul-de-sac of New Zealand White rabbit eyes 3 times at 15-minute intervals. The drug concentrations in(the anterior sac aqueous,: this is wrong) the aqueous humor 10, 30, 60, 120 and 240 minutes after the final instillation were examined by high performance liquid chromatography(HPLC) and/or bioassay. The AQCmax was calculated using the one-compartment method. RESULTS: The calculated AQCmax was 2.5 micrograms/ml (HPLC method) and 2.28 micrograms/ml (Bioassay Method) for LVFX, 2.17 micrograms/ml for CP, and 0.45 microgram/ml for EM. The AQCmax for CMX, MCR and SBPC could not be calculated by the one-compartment method. CONCLUSION: The AQCmax of LVFX was higher than that of the 2 other general purpose antimicrobial ophthalmic solutions. The AQCmax of these drugs might be a useful parameter for selecting an appropriate ophthalmic solution for the treatment of infected eyes.

Effects of the quantity of water and milk ingested concomitantly with AS-924, a novel ester-type cephem antibiotic, on its pharmacokinetics.

The effect of the quantity of water ingested concomitantly with drugs, on the absorption of AS-924, a novel prodrug-type cephem antibiotic, was studied in five healthy adult volunteers by a cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. In addition, the effect of milk on the absorption of AS-924 was also investigated. The absorption of CTER-PI was significantly reduced when administered together with 30 ml of water compared with its absorption when administered together with 150 ml of water, whereas no such reduction was found in the case of AS-924. Ingestion of milk did not significantly affect the absorption of AS-924. These results confirm that absorption of AS-924 after oral administration is not likely to be affected by the quantity of water taken concomitantly with the drug, nor by milk.

Effect of antacid pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic--comparison with cefteram-pivoxil.

The effect of pretreatment with ranitidine, an antacid, on the absorption of AS-924, a novel prodrug-type cephem antibiotic derived from ceftizoxime (CTIZ), was examined in eight healthy adult male volunteers by the cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. The C(max) and area under the concentration (AUC) values and cumulative urinary excretion rate (0-24 h) of cefteram (CTER) after administration of CTER-PI decreased by 32, 38 and 37%, respectively, in the ranitidine pretreatment group whereas those of AS-924 were not affected by the antacid. The urinary levels of pivaloyl-carnitine determined to evaluate the solubility of these antibiotics in the gastrointestinal tract suggested that this was not affected by ranitidine. These results indicate that the absorption of CTER-PI was affected by pretreatment with ranitidine largely due to inactivation of this antibiotic in the gastrointestinal tract at high pH rather than to a decrease in solubility. In contrast, isomerization of AS-924 was hardly induced by the elevation of pH, thus demonstrating that AS-924 was less likely to be affected by pretreatment with antacids.

Effect of side chains including the N-methyl-tetrazole-thiol group of beta-lactam antibiotics on transport in cultured kidney epithelial cells LLC-PK1.

In this study, the transcellular transport characteristics of four beta-lactam antibiotics (cefotaxime, cefmenoxime, cefmetazole, and cefotiam) were investigated in a kidney epithelial cell line LLC-PK1, especially focusing on the effect of the N-methyl-tetrazole-thiol (NMTT) group attached to 7-amino-cephalosporanic acid. There were no directional differences between the apical-to-basolateral and basolateral-to-apical transport of cefotaxime, cefmenoxime, and cefmetazole, suggesting that the NMTT group does not influence the transcellular transport behaviors of beta-lactam antibiotics. In contrast, cefotiam transport across LLC-PK1 cell monolayers was 1.3-fold greater in the basolateral-to-apical direction than in the apical-to-basolateral direction. It is considered that the ionization of nitrogen in the N-dimethylaminoethyl group attached to NMTT is a factor in the secretory-oriented movement of cefotiam. The transcellular transport of cefotiam in both directions was significantly depressed at a low temperature (4 degrees C) and by 2,4-dinitrophenol. The basolateral-to-apical transport of cefotiam was also shown to be concentration-dependent. These results suggest that a specialized transport process might participate in the transcellular transport of cefotiam. The lipophilicities of these beta-lactam antibiotics were not correlated to the degree of transcellular transport, directly.

Intracameral levels of intravenously injected fluorescein, cefmenoxime, and chloramphenicol in the prostaglandin E2-administered eyes of albino rabbits.

We evaluated the effects of inflammation and physicochemical nature of selected agents on the intracameral levels of intravenously injected drugs in albino rabbits. Transcorneal diffusion of prostaglandin E2 (10, 50 or 250 micrograms/ml) using a glass cylinder was used to produce inflammation of the anterior segment in the right eyes. As a control, a vehicle was applied to the left cornea. Immediately, 2, 5, or 11 h after prostaglandin E2 administration, a mixed solution of fluorescein, cefmenoxime, and chloramphenicol (50 mg each/kg body weight) was injected intravenously. One hour after injection of the drugs, the primary aqueous humor was withdrawn. The intracameral levels of protein and these drugs after prostaglandin E2 administration increased at 1 h in a dose-dependent manner. These levels then gradually decreased. One hour after prostaglandin E2 administration, the intracameral levels of protein and these drugs in the prostaglandin E2-administered eyes were significantly higher than those in the vehicle-administered eyes, except chloramphenicol after administration of 10 micrograms/ml prostaglandin E2. Our findings indicate that the intracameral levels of intravenously administered drugs are altered not only by the severity of inflammation but also by the properties of drugs.

Modeling the response of pneumonia to antimicrobial therapy.

The response to antimicrobial therapy in patients with pneumonia was assessed by using a previously developed pneumonia scoring system. Patients from two different clinical trials were evaluated. The first group (n = 22) was treated with cefmenoxime. For these patients, doses were adjusted to achieve an area under the plasma concentration-versus-time curve (AUC) above the MIC of 140 microg x h/ml and pneumonia response scores were evaluated retrospectively. The second group (n = 21) were treated with either ciprofloxacin (CIP) or ceftazidime (TAZ) in a randomized clinical trial. Here, doses were adjusted to achieve AUC from 0 to 24 h/MIC values that were > 250 SIT(-1) x h (estimate of the area under the curve of inverse serum inhibitory titer versus time) and pneumonia response scoring was concurrent. In both studies eradication of the pathogen was determined by serial endotracheal cultures and clinical parameters were scored daily. A decrease in total score was indicative of an improving clinical condition. The percent change in clinical daily score was determined for each day of treatment. The rate of clinical response was determined by linear regression of the percent change in daily clinical score versus time during the course of antimicrobial therapy. Factors predictive of time to eradication were explored by interval analysis. Logistic regression was used to determine the earliest time point in therapy at which treatment scores predicted outcome. Kruskal-Wallis analysis of variance was used for statistical analysis, and significance was accepted at P < 0.05. There were no differences in baseline scores at day one for the patients treated with different antibiotics (P = 0.58). For patients with pathogen eradication, a significant difference between the two studies in time to eradication was found: 4.8 days for cefmenoxime-treated patients and 1.4 days for CIP- or TAZ-treated patients (P < 0.001). For patients experiencing bacterial eradication, the rates of clinical change for cefmenoxime and CIP or TAZ treatment were similar (P = 0.77). For patients with organisms that were not eradicated, the rates of change were similar (P = 0.14). There was a significant difference in the rate of change for patients experiencing eradication compared with that for patients in which the organism persisted (P << 0.01). Both treatment group and rate were found to be predictive of days to eradication. There was a significant difference in the percent change in clinical score on day 3 of therapy for patients with bacteria that were eradicated versus those with persistent organisms (P < 0.01). The percent change was more predictive of outcome with each subsequent day. Patients who demonstrated a > or = 10% reduction in clinical score after 72 h of treatment had an 88% probability of bacterial eradication. The clinical scoring system is a useful tool for modeling the response of pneumonia to antimicrobial therapy. The ability to predict outcome relatively early in therapy, by using a scoring system of clinical parameters which can be routinely monitored, will aid in assessing the response to antimicrobial therapy in clinical as well as in research settings.

AUIC--a general target for the optimization of dosing regimens of antibiotics?

OBJECTIVE: To present a systematic evaluation of the are under the inhibitory curve (AUIC) approach for the optimization of antibiotic dosing schedules for three major antibiotic classes (beta-lactams, quinolones, aminoglycosides). It has been proposed that an AUIC over 24 hours of at least 125 may be an applicable target parameter for the optimization of antibiotic dosing schedules across these antibiotic classes. Some limitations of this approach are presented and discussed. METHODS: A precise equation for the calculation of AUIC is derived. Moreover, a specific equation is derived for the situation that results in a trough concentration at the end of the dosing interval equal to the minimum inhibitory concentration (MIC). With the same three drugs used for deriving the target AUIC value (tobramycin, cefmenoxime, ciprofloxacin), different dosing regimens are simulated to obtain the target AUIC of 125. RESULTS: Very different serum concentration profiles can result in the same AUIC. In an example for cefmenoxime, dosing regimens of 1 g q6h and 4.2 g q24h resulted in equal AUIC values of 125, whereas the respective time above MIC differed dramatically (99% of the dosing interval for q6h vs. 36% for q24h). CONCLUSIONS: It does not seem valid to accept the proposed breakpoint AUIC target of at least 125 as an applicable value for determining the appropriate dosing schedule of these classes of antibiotics. Based on the limitations discussed about the AUIC approach, the same conclusion also holds for any other fixed AUIC breakpoint target value.

[Pharmacokinetics of subconjunctivally injected drugs in the anterior segment of rabbit eyes].

We injected 12.5, 25, 50 and 100 microliters portions of a combined solution of 2.5% sodium fluorescein (FL), 2.5% cefmenoxim hemihydrochloride (CMX), and 0. 25% chloramphenicol (CP) subconjunctivally into rabbit eyes by various methods. Drug levels were monitored in the tears and aqueous humor and measured via high performance liquid chromatography. In the tear fluid, the concentrations of CP decreased more rapidly with time than FL and CMX. The drugs penetrated the rabbit's eyes better when injected subconjunctivally than when administered by sub-Tenon's injection. After subconjunctival injection through the eyelid, the drug concentration in the tears decreased with time in almost the same way as for injection through the conjunctival membrane. There was little difference between the presence and absence of a puncture hole in the conjunctiva. When the whole cornea was sealed with cyanoacrylate glue to block transcorneal absorption, the FL concentration in the aqueous humor was 30% of that in the control and the CP concentration was less than 10% of that in the control. About 70% of FL penetrating the eyes was derived from the transcorneal route but most of the CP was derived from the transcorneal route. FL in 1% or 0. 25% sodium hyarulonate (HA) and saline was injected subconjunctivally, and the concentrations of FL in the cornea and vitreous humor were measured. FL in 0.25% HA penetrated rabbit eyes better than that in 1% HA. These findings suggest that by dissolving the drug in an adequate concentration of HA solution, better penetration of drugs into the eye can be obtained.

Elimination of cefmenoxime during continuous haemofiltration.

The elimination of cefmenoxime after single and repeated i.v. dosing was studied in 12 patients with severe renal failure and sepsis during continuous haemofiltration. More than 30% of the drug was found in the filtrate. The sieving coefficient (S) was 0.54. Vss% was unchanged 0.31 l.kg-1 in comparison with patients with normal renal function, whereas the mean t1/2ss was prolonged to about 16 h, and total clearance was reduced 20.8 ml.min-1.1.73 m-2. Once daily administration of 1 g cefmenoxime is suggested as the appropriate dose under such circumstances.

[The dynamics of melanin-affinitive and non-affinitive antibacterial agents in the iris-ciliary body of rabbit eyes--comparative studies in pigmented and albino rabbits].

The differences between the drug penetration levels in the iris-ciliary bodies of sparfloxacin (SPFX) and cefmenoxime (CMX), which respectively have high and low affinity to melanin, were examined using pigmented and albino rabbit eyes. Each drug was mixed with a homogenate of the iris-ciliary bodies of pigmented and albino rabbit eye, respectively. All CMX was distributed in a water soluble protein of the above homogenate of both pigmented and albino eyes, while all SPFX was detected from the water soluble protein of the tissue homogenate of the albino eye. However, in homogenate of the pigmented eyes, 60% of the drug was detected from water soluble protein and 20% of that was detected from water non-soluble protein. In the in vivo study, each drug was topically administered to pigmented and albino rabbit eyes. The SPFX concentration in the iris-ciliary body was significantly higher in the pigmented than in the albino eyes. The results indicated that the intraocular dynamics of the drug which has a high affinity to melanin showed significant differences between pigmented and albino rabbit eyes. This should be considered in studies of ocular pharmacology as an important factor which influences intraocular drug dynamics.

Diffusion of cefmenoxime and latamoxef into prostatic fluid in the patients with acute bacterial prostatitis.

Twenty-two patients with acute bacterial prostatitis were treated with cefmenoxime (CMX) or latamoxef (LMOX), which have susceptibilities against various gram-negative bacteria. First 11 patients received a 5- to 12-day course of cefmenoxime and the next 11 received a 6- to 13-day course of latamoxef. All patients were treated successfully except 1 patient with a drug allergy. Diffusion of CMX or LMOX into prostatic fluid in these patients and healthy controls were evaluated. The mean value of CMX in the expressed prostatic fluid was 12.8 micrograms/ml in the patients receiving 2 g of CMX intravenously and 0.7 micrograms/ml in the controls. The mean value of LMOX was 14.0 micrograms/ml in the patients receiving 2 g of LMOX intravenously and 1.2 micrograms/ml in the controls. The diffusion of CMX and LMOX into prostatic fluid in the patients with acute bacterial prostatitis was strikingly higher than that of controls.

Cerebrospinal fluid penetration of cefmenoxime in children with bacterial meningitis.

Blood and cerebrospinal fluid (CSF) concentrations of cefmenoxime were determined either microbiologically or by means of HPLC in 20 children with proven or suspected bacterial meningitis. Sixteen children suffered from bacterial meningitis: causative organisms were Haemophilus influenzae type b (n = 10), Streptococcus pneumoniae (n = 4) and Neisseria meningitidis (n = 2). In these patients the cefmenoxime concentration in the CSF ranged from 0.9 to 12.2 mg/l, with a mean concentration of 4.63 mg/l 1.5-3 h after the last intravenous cefmenoxime application and 24-48 h after initiating therapy with 200 mg cefmenoxime/kg/d in four doses. In eight cases the bactericidal titers of the CSF were examined during therapy. Titers between 1:64 and 1:2,048, exceeding the minimal bactericidal concentration, were found. After five doses of cefmenoxime 50 mg/kg, two CSF cultures showed bacterial growth: one H. influenzae (bactericidal titer in CSF 1:256) and one S. pneumoniae.

[Cefmenoxime penetration in human lacrimal sac mucosa after systemic administration]. / Cefmenoxim-Penetration in die menschliche Tränensackschleimhaut nach systemischer Applikation.

Access to microbiological, pharmacokinetic and toxicological information is necessary for useful, controlled application of antibiotics in intraocular and periocular infections. It is important to know whether the antibiotic is effective against ophthalmologically relevant bacteria and if suprathreshold concentrations of the antibiotic can be achieved in the contaminated tissue. In the study presented we investigated the usefulness of cefmenoxime in cases of dacryocystitis. Lacrimal sac tissue--and serum specimens were obtained from 15 patients who underwent dacryocystorhinostomy 0.5 to 13 h after intravenous injection of 25 mg cefmenoxime kg. The usual Toti procedure was performed in 7 patients, whereas the other 8 underwent endonasal surgery. Out of the 15 patients 12 suffered from recurrent dacryocystitis. Before application of the antibiotic a serum control sample was obtained in all patients. The highest cefmenoxime levels in the lacrimal sac (72 mg/kg) were measured 30 min after injection. Thirteen hours after the injection, the cefmenoxime levels were too low to be measured. The levels of cefmenoxime in the lacrimal sac tissue were compared with the minimal inhibitory concentrations for the frequent occurrence of bacteria in lacrimal sac infections.

[Diffusion of cefmenoxime into prostatic fluid in the patients with acute bacterial prostatitis].

Expressed prostatic fluid (EPS) levels and serum levels of cefmenoxime (CMX) after intravenous administration were examined in 16 patients with acute bacterial prostatitis and 23 patients without prostatic diseases. Blood was drawn at 30, 60, 120 minutes and EPS was taken by prostatic massage at 60 minutes after the intravenous administration of 2 g CMX to evaluate the concentration of CMX. The concentration of CMX was determined by the bioassay using the E. coli NIHJ JC strain. The relationships between the EPS/serum ratio and peripheral WBC counts, CRP value and ESR 1h value were also analyzed. The serum levels of CMX at 60 minutes ranged between 20.3 micrograms/ml and 73.5 micrograms/ml (mean +/- S.D.: 41.8 +/- 14.2 micrograms/ml) in 16 patients with acute prostatitis, and between 21.5 micrograms/ml and 89.5 micrograms/ml (mean +/- S.D.: 49.5 +/- 18.7 micrograms/ml) in 23 patients without prostatic diseases. The EPS levels ranged between 0.4 micrograms/ml and 30.8 micrograms/ml (mean +/- S.D.: 12.6 +/- 9.6 micrograms/ml) in 16 patients with acute prostatitis, and between 0 and 2.3 micrograms/ml (mean +/- S.D.: 0.7 +/- 0.8 microgram/ml) in 19 patients without prostatic diseases. In 4 patients without prostatic diseases, the EPS amount was not large enough to evaluate the concentration of CMX. The EPS/serum ratio ranged between 0.006 and 0.697 (mean +/- S.D.: 0.31 +/- 0.21) in patients with acute prostatitis and between 0 and 0.058 (mean +/- S.D.: 0.015 +/- 0.018) in patients without prostatic diseases. The diffusion of CMX into the prostatic fluid in patients with acute prostatitis was strikingly higher than that in patients without prostatic diseases (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of antacids on absorption, excretion and metabolism of cefteram pivoxil].

Effects of various antacids (sodium bicarbonate, aluminium hydroxide gel) and an H2-blocker (cimetidine) on the absorption and excretion of a new cephem drug for oral use, cefteram pivoxil (CFTM-PI), were studied in healthy adult volunteers. 1. No significant differences were found in serum levels of CFTM and CFTM-A (an inactive isomer of cefteram (CFTM)) or their urinary excretion levels (concentration, recovery rate) between the group given CFTM-PI in combination with sodium bicarbonate and that given CFTM-PI alone. 2. There were no significant differences in serum levels of CFTM and CFTM-A or their urinary excretion levels (concentration, recovery rate) between the group given CFTM-PI in combination with aluminium hydroxide gel and that given CFTM-PI alone. 3. In contrast, serum levels of CFTM and its urinary recovery rate were significantly less in the group given the drug in combination with cimetidine than in that given a single administration 2-3.5 hours and 2-4 hours after administration, respectively. Clinical considerations remain.

Paradoxical activity of beta-lactam antibiotics against Proteus vulgaris in experimental infection in mice.

In previous papers (Y. Ikeda and T. Nishino, Antimicrob. Agents Chemother. 32:1073-1077, 1988; Y. Ikeda, T. Nishino, and T. Tanino, Antimicrob. Agents Chemother. 31:865-869, 1987), we reported that many of the 7-aminothiazolyl cephalosporins, such as cefmenoxime, showed paradoxically reduced activity against Proteus vulgaris at higher concentrations, whereas these paradoxical effects were not observed for other types of cephalosporins, such as cefbuperazone and cefoperazone. In this study, we compare the therapeutic effect of cefmenoxime with that of cefbuperazone and explore the in vivo paradoxical effect of cefmenoxime by using an experimental infection model in mice. In an intraperitoneal infection with P. vulgaris 11, the survival rate with cefmenoxime was increased to 43% at 3.13 mg/kg but was lower at higher doses. On the other hand, cefbuperazone did not show such a paradoxical therapeutic effect. In mice infected with P. vulgaris 11, cefmenoxime levels in both serum and peritoneal washings were rapidly reduced and beta-lactamase activities in the peritoneal cavity were increased at higher cefmenoxime doses. These findings suggested that high levels of cefmenoxime at the infection site induced increased production of beta-lactamase, which then rapidly inactivated the antibiotic. We conclude that the paradoxical therapeutic effect of cefmenoxime against P. vulgaris occurs by the same mechanisms as the in vitro effect and that the high beta-lactamase inducibility and low beta-lactamase stability may account for the paradoxical therapeutic effect of cefmenoxime against P. vulgaris.