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Pharmacological properties of cephalosporins.

The cephalosporins differ in the substituents attached at the 3 and/or 7 positions of the molecule. Very schematically, substitution at C3 mainly modifies the overall pharmacokinetic properties whereas substitution at position 7 influences the antibacterial characteristics. When using the more common "generation" system for classification, three generations can be distinguished on the basis of their antibacterial spectrum, potency, and their stability to beta-lactamases. The first generation cephalosporins have similar antibacterial and pharmacokinetic characteristics. C3-esterified cephalosporins (e.g. cephalothin and cephapirin) are significantly metabolized. The so-called second generation cephalosporins exhibit only minor differences with respect to the pharmacokinetic properties in contrast to the third generation cephalosporins. The apparent volumes of distribution of most cephalosporins range between seven and 20 1, indicating that they mainly stay in the extracellular space. Plasma protein binding is variable from compound to compound. Generally, the major route of elimination of most cephalosporins is via the kidney except for cefoperazone and ceftriaxone which are both excreted to a large extent by the biliary route. With the exception of cefonicid, cefotetan and cefriaxone, which have longer elimination half-lives (i.e. 4.5, 3.5 and around eight hours), all other cephalosporins have a half-life ranging from 0.5 to 2.5 hours. The pattern of adverse reactions is comparable for all the cephalosporins although there are slight differences in both the incidence and the type of reactions. The major categories of adverse reactions are gastrointestinal, dermatologic, hypersensitivity, haematologic, hepatic, renal as well as CNS effects. Alcohol intolerance (antabus-like effect) can occur when cephalosporins containing the NMTT moiety are administered concomitantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Identification and separation of five cephalosporins by micellar electrokinetic capillary chromatography.

The cephalosporins are a group of structurally related, broad spectrum beta-lactam antibiotics isolated from the mold Cephalosporium. Methods of analysis of cephalosporin antibiotics include microbiological, titrimetric and chromatographic assays. Chromatographic techniques, including high-performance liquid chromatography, have been extensively utilized for specific and sensitive assays of beta-lactam antibiotics in a variety of matrices, i.e. clinical and pharmaceutical. Several of the drawbacks of HPLC in the analysis of cephalosporins in food and biological samples include matrix interferences and low resolution due to column adsorption. Recently, the applicability of capillary electrophoresis to the resolution of beta-lactam antibiotics has been demonstrated in the literature. In this paper we employed sodium borate and an anionic surfactant, sodium dodecyl sulfate (SDS), in a separation technique called micellar electrokinetic capillary chromatography with UV detection, to resolve a mixture of five cephalosporins--cefuroxime, cephalexin, cephapirin, cefamandole nafate and cephalothin. The presence of SDS in the running buffer above the critical micelle concentration, creates a pseudostationary phase enabling high-efficiency chromatographic separations. The effect of the ion-pairing reagent, pentanesulfonic acid sodium salt, on the resolution of the cephalosporin mixture in conjunction with SDS was also examined.

Cephalosporins↗

In vitro susceptibility of Mycobacterium avium complex to antibacterial agents.

In vitro agar dilution susceptibility studies were performed utilizing 20 isolates (24 against rifamycin) of Mycobacterium avium complex against several antimicrobial agents not routinely tested in the mycobacteriology laboratory. Thirteen strains were susceptible to gentamicin at 4 micrograms/ml, 20 to amikacin at 8 micrograms/ml, 18 to streptomycin at 8 micrograms/ml, 20 to kanamycin at 8 micrograms/ml, 20 to trimethoprim/sulfamethoxazole at 2 micrograms/ml, 12 to sulfisoxazole at 10 micrograms/ml, 14 to rifabutin at 1 microgram/ml. No activity was found with penicillin G, cephapirin, moxalactam, vancomycin, clindamycin, erythromycin, trimethoprim, or minocycline. This data suggests a potential use of trimethoprim/sulfamethoxazole, sulfisoxazole, amikacin, gentamicin, and kanamycin in the treatment of infections caused by this group of organisms.

Anti-Bacterial Agents↗

Effects of surface-active agents on drug susceptibility levels and ultrastructure of Mycobacterium avium complex organisms isolated from AIDS patients.

The multiple-drug-resistance property of Mycobacterium avium complex (MAC) is mainly attributed to a cell envelope permeability barrier. MAC treated with subinhibitory levels of dimethyl sulfoxide (DMSO) and ethylenediaminetetraacetic acid (disodium salt) (EDTA) did not have altered minimum inhibitory concentration (MIC) levels or show ultrastructural changes; the effect of sodium dodecyl sulfate (SDS) was variable. With SDS, the visualization of the nucleoid and ribosomes decreased, and amorphous electron-dense material accumulated near the structurally altered cytoplasmic membrane and cell wall. Use of 0.005% Tween-80 resulted in a 2-4-fold reduction in MIC in the case of rifampicin, ansamycin (LM 427), cephapirin, and ciprofloxacin. Tween-80 treated cells were swollen, and deposits of low electron-density accumulated in the cytoplasm; distortions in the outer-cell integuments were observed. These findings are consistent with the idea that Tween-80 increases cell-envelope permeability, thereby enhancing drug penetrability and reducing MIC levels. Because of the action of Tween-80, its use in drug-susceptibility media or diluent fluids should be avoided.

Acquired Immunodeficiency Syndrome↗

Trace determination of beta-lactam antibiotics in surface water and urban wastewater using liquid chromatography combined with electrospray tandem mass spectrometry.

A sensitive and reliable method using liquid chromatography-electrospray tandem mass spectrometry has been developed and validated for the trace determination of beta-lactam antibiotics in natural and wastewater matrices. Water samples were enriched by solid-phase extraction. The analytes included amoxicillin (AMOX), ampicillin (AMP), oxacillin (OXA), cloxacillin (CLOX) and cephapirin (CEP). Average recoveries of beta-lactams (BLs) in fortified samples were generally above 75% (except amoxicillin) with the standard deviations lower than 10% in water matrices. Amoxicillin was not quantified due to poor recovery (less than 40%) in the investigated water matrices. Matrix effects were found to be minimal when measuring these compounds in water matrices. The accuracy, within- and between-run precision of the assay fell within acceptable ranges of 15% absolute. The method detection limit (MDL) was estimated to range between 8 and 10 ng/L in surface water, 13 and 18 ng/L in the influent and 8 and 15 ng/L in the effluent from a wastewater treatment plant. A large number of actual water samples were analyzed using this method in order to evaluate the occurrence of the beta-lactams in a river and a wastewater treatment plant in northern Colorado. Most of the samples were negative for all analytes. These compounds were found at 15-17 ng/L in the three influent samples and at 9-11 ng/L in three surface water samples out of a total of 200 samples. This indicates that contamination by beta-lactam antibiotics is of minor importance to the small mixed-watershed.

Anti-Bacterial Agents↗

Characterization of cephalosporin transfer between aqueous and colloidal phases by micellar electrokinetic chromatography.

A new electrokinetic chromatographic method was applied to the determination of the partition coefficient between water and micelle for a group of cephalosporins (cefmetazol, cephradin, cefaclor, ceftazidim, cefodizim, cephapirin, cephalothin and ceftriaxon) using sodium dodecyl sulphate as an anionic surfactant in microemulsion and in micellar systems. In the new method, the running buffer contains both the micelles and the drug, and the injected solution contains the same concentration of micelles as the running buffer but not the drug. The mobility of the drug can be measured from a negative peak recorded the chromatogram. The required parameters for the determination of the capacity factor (mu(aq) and /mu(me) are the electrophoretic mobilities of the solutes in the aqueous and the micelle phases, mu(eff) is the effective mobility in the micellar system or in the microemulsion) were measured by the new micellar and microemulsion electrokinetic chromatography technique. Linear log-log relationships were found between both the micelle-water partition coefficient and the capacity factor and the n-octanol-water partition coefficient.

Cephalosporins↗

Characterization of partition and thermodynamic properties of cephalosporins using micellar electrokinetic chromatography in glycodeoxycholic acid solution.

Micellar electrokinetic chromatography (MEKC) was introduced to evaluate the hydrophobicity of cephalosporins (cefpim, cefpirom, cefazolin, ceftazidim, cephradin, cefuroxim, cefotaxim, cephapirin and cephalothin). Partition coefficients of cephalosporins were calculated between a micelle and an aqueous phases from the measurement of the migration time, provided the critical micelle concentration and the phase ratio are known. Thermodynamic quantities such as enthalpy and entropy changes of micellar solubilization were calculated from the temperature dependence on the partition coefficients. Sodium glycodeoxycholate in low-salt aqueous solutions was employed to prepare a micellar solution. Substances for pharmaceutical purposes have to meet several requirements to be well-tolerated. Therefore, they are often derived from naturally occurring ones, e.g., from the bile salts in bile juice. The electrophoretic velocity of a micelle and the phase ratio between the micelle of the glycodeoxycholic acid and the aqueous phase were calculated. Partial specific volumes at different temperatures (from 20 to 45 degrees C) were measured using dynamic light scattering. The logarithm of the partition coefficients and the migration factor in the micellar system were correlated with the logarithm of the 1-octanol-water partition coefficients.

Cephalosporins↗

Acalculous cholecystitis and septicemia caused by non-O1 Vibrio cholerae: first reported case and review of biliary infections with Vibrio cholerae.

The first case of septicemic acute acalculous cholecystitis caused by non-O1 Vibrio cholerae is described in a healthy traveler, and biliary tract infections from V. cholerae are reviewed. Immediately after a vacation in Cancun, Mexico, a 55-year-old man developed acute cholecystitis. Blood and bile cultures grew non-O1 V. cholerae. At surgery, the gallbladder was acalculous, inflamed, distended, and nearly ruptured. Pathogenetic factors may have included diarrhea prophylaxis with bismuth subsalicylate, distension of the gallbladder from illness-induced fasting, and bacterial toxins in the gallbladder. The patient received i.v. cephapirin, followed by oral cephradine for a total of 10 days, and he made a quick and complete recovery. V. cholerae should be considered in the differential diagnosis of persons from endemic areas who present with cholecystitis or acute jaundice.

Bacteremia↗

Determination of beta-lactam residues in milk using perfusive-particle liquid chromatography combined with ultrasonic nebulization electrospray mass spectrometry.

The introduced electrospray (ESP) technique combined with quadrupole mass spectrometry (MS) was applied for the trace residue detection (10 ppb) of commonly administered beta-lactam antibiotics in bovine milk. Because of the widespread use of penicillin G, ampicillin, amoxicillin, cephapirin, cloxacillin, and ceftiofur in veterinary medicine, these six popular drugs were chosen to develop a fast and reliable microcolumn liquid chromatographic (micro-LC) separation method for residue-containing milk extracts. Furthermore, the analytes were selected to test the chromatographic behavior of a novel stationary phase, a perfusive-particle column packed with derivatized porous polystyrene divinylbenzene. The effects of mobile phase additives on separation and ESP ionization efficiency were investigated. The ionization of the eluted analytes took place either in a conventional ESP interface with a capillary shield allowing flow rates up to 40 microL/min or in the latest model of the ultrasonic nebulization ESP interface. The perfusive-particle column, although not optimized for the separation of small molecules, exhibited sufficient resolution of the antibiotics for its routine usage, especially when considering the remarkable time-saving advantage compared with ordinary reversed phase micro-LC columns. The application of the novel ultrasonic nebulization interface lowered detection limits and improved the stability of the signals over a much wider flow rate range than possible for ionization with the ESP system equipped with the conventional needle.

Animals↗

Confirmatory and quantitative analysis of beta-lactam antibiotics in bovine kidney tissue by dispersive solid-phase extraction and liquid chromatography-tandem mass spectrometry.

A simple, rapid, rugged, sensitive, and specific method for the confirmation and quantitation of 10 beta-lactam antibiotics in fortified and incurred bovine kidney tissue has been developed. The method uses a simple solvent extraction, dispersive solid-phase extraction (dispersive-SPE) cleanup, and liquid chromatography-tandem mass spectrometry (LC/MS/MS) for confirmation and quantitation. Dispersive-SPE greatly simplifies and accelerates sample cleanup and improves overall recoveries compared with conventional SPE cleanup. The beta-lactam antibiotics tested were as follows: deacetylcephapirin (an antimicrobial metabolite of cephapirin), amoxicillin, desfuroylceftiofur cysteine disulfide (DCCD, an antimicrobial metabolite of ceftiofur), ampicillin, cefazolin, penicillin G, oxacillin, cloxacillin, naficillin, and dicloxacillin. Average recoveries of fortified samples were 70% or better for all beta-lactams except DCCD, which had an average recovery of 58%. The LC/MS/MS method was able to demonstrate quantitative recoveries at established tolerance levels and provide confirmatory data for unambiguous analyte identification. The method was also tested on 30 incurred bovine kidney samples obtained from the USDA Food Safety and Inspection Service, which had previously tested the samples using the approved semiquantitative microbial assay. The results from the quantitative LC/MS/MS analysis were in general agreement with the microbial assay for 23 samples although the LC/MS/MS method was superior in that it could specifically identify which beta-lactam was present and quantitate its concentration, whereas the microbial assay could only identify the type of beta-lactam present and report a concentration with respect to the microbial inhibition of a penicillin G standard. In addition, for 6 of the 23 samples, LC/MS/MS analysis detected a penicillin and a cephalosporin beta-lactam, whereas the microbial assay detected only a penicillin beta-lactam. For samples that do not fall into the "general agreement" category, the most serious discrepancy involves two samples where the LC/MS/MS method detected a violative level of a cephalosporin beta-lactam (deacetylcephapirin) in the first sample and a possibly violative level of desfuroylceftiofur in the second, whereas the microbial assay identified the two samples as having only violative levels of a penicillin beta-lactam.

Animals↗

Molecular engineering of fluorescent penicillins for molecularly imprinted polymer assays.

The interaction of seven novel fluorescent labeled beta-lactams with a library of six polymer materials molecularly imprinted (MI) with penicillin G (PenG) has been evaluated using both radioactive and fluorescence competitive assays. The highly fluorescent competitors (emission quantum yields of 0.4-0.95) have been molecularly engineered to contain pyrene or dansyl labels while keeping intact the 6-aminopenicillanic acid moiety for efficient recognition by the cross-linked polymers. Pyrenemethylacetamidopenicillanic acid (PAAP) is the tagged antibiotic that provides the highest selectivity when competing with PenG for the specific binding sites in a MI polymer prepared with methacrylic acid and trimethylolpropane trimethacrylate (10:15 molar ratio) in acetonitrile in the presence of PenG. Molecular modeling shows that recognition of the fluorescent analogues of PenG by the MI material is due to a combination of size and shape selectivity and demonstrates how critical the choice of label and tether chain is. PAAP has been applied to the development of a fluorescence competitive assay for PenG analysis with a dynamic range of 3-890 muM in 99:1 acetonitrile-water solution. Competitive binding studies demonstrate various degrees of cross-reactivity for some antibiotics derived from 6-aminopenicillanic acid, particularly amoxicillin, ampicillin, and penicillin V (but not oxacillin, cloxacillin, dicloxacillin, or nafcillin). Other antibiotics, such as chloramphenicol, tetracycline, or cephapirin, do not compete with PAAP for binding to the imprinted polymer. The MI assay has successfully been tested for PenG analysis in a pharmaceutical formulation.

Binding, Competitive↗

Synthesis and screening of a molecularly imprinted polymer library targeted for penicillin G.

A library of molecularly imprinted polymers (MIPs) was synthesized by radical bulk polymerization using the beta-lactam antibiotic penicillin G as the template. Diversity of the library was obtained by combining various functionalized monomers and cross-linkers and by varying the stoichiometry and the concentration of the components in the prepolymerization mixtures. The library was screened for selectivity to penicillin G by a radioligand binding assay and was compared to a corresponding control library. The best MIP candidate, showing the highest selectivity for penicillin G, was prepared from methacrylic acid and trimethylolpropane trimethacrylate as the functionalized monomer and cross-linker, respectively. Cross-reactivity studies with other beta-lactam antibiotics showed a low cross-reactivity of penicillin V (15%), ampicillin (16%), and amoxicillin (19%). Nafcillin and oxacillin showed less cross-reactivity (<1%). Cross-reaction with a cephalosporin antibiotic (cephapirin) and structurally nonrelated antibiotics (chloramphenicol, tetracycline, dapsone, and erythromycin) was less than 0.01%.

Anti-Bacterial Agents↗

Development of a novel and automated fluorescent immunoassay for the analysis of beta-lactam antibiotics.

An automated immunosensor for the rapid and sensitive analysis of penicillin type beta-lactam antibiotics has been developed and optimized. An immunogen was prepared by coupling the common structure of the penicillanic beta-lactam antibiotics, i.e., 6-aminopenicillanic acid to keyhole limpet hemocyanin. Polyclonal antibodies raised in rabbits after immunization with this conjugate have been applied for the development of a competitive fluoroimmunoassay (FIA), using a novel fluorescent penicillin {[2S,5R,6R]-3,3-dimethyl-7-oxo-6-[(pyren-1ylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxilic acid, PAAP} as the tracer and penicillin G as the reference antibiotic. Protein A/G covalently bound to an azlactone-activated polymeric support was used for the orientated capture of the antibody-antigen immunocomplexes. Upon desorption from the immunosupport, the emission signal generated by the PAAP-Ab complexes is related to the antibiotic concentration in the sample. The 50% binding inhibition concentration of penicillin G standard curves was at 30 ng mL(-)(1) with a detection limit (10% binding inhibition) of 2.4 ng mL(-)(1) and a dynamic range from 6.0 to 191 ng mL(-)(1) (20-80% binding inhibition) penicillin G. The generic nature of the antiserum was shown by good relative cross-reactivities with penicillin type beta-lactam antibiotics such as amoxicillin (50%), ampicillin (47%), and penicillin V (145%) and a lower response to the isoxazolyl penicillins such as oxacillin, cloxacillin, and dicloxacillin. No cross-reactivity was obtained for cephalosporin type beta-lactam antibiotics (cephapirin), cloramphenicol, or fluoroquinolones (enrofloxacin and ciprofloxacin). The total analysis time was 23 min per determination, and the immunoreactor could be reused for more than 200 cycles without significant loss of activity. The immunosensor has been successfully applied to the direct analysis of penicillin G and amoxicillin in spiked influent and effluent sewage treatment plant water samples with excellent recoveries (mean values for penicillin G and amoxicillin, 99 and 105%, respectively). Results displayed by comparative analysis of the immunosensor with a chromatographic procedure for penicillins showed excellent agreement between both methods.

Anti-Bacterial Agents↗

Evaluation of liquid chromatographic behavior of cephalosporin antibiotics using restricted access medium columns for on-line sample cleanup of bovine milk.

Microsample deproteinization of bovine milk was carried out on-line using a series of restricted access medium (RAM) bovine serum albumin (BSA) columns: C8, C18, phenyl, and cyano. The four different columns prepared showed a high percentage of protein exclusion using water as the mobile phase and provided an appropriate retention profile for a series of five cephalosporin antibiotics (cefoperazone, cephacetril, cephalexin, cephapirin, and ceftiofur). Chromatographic conditions such as washing time, buffer pH, and type and percentage of organic modifier were fully evaluated with respect to the protein elution profile and retention of the antibiotic by RAM column. One of these columns was chosen to develop and validate a method for the determination of cefoperazone in bovine milk. The system used in this work was composed of a RAM-BSA phenyl column coupled to a C18 analytical column. The standard curve was linear over the range 0.100-2.50 microg/mL. The limits of quantification and detection were 0.100 and 0.050 microg/mL, respectively. The developed method showed high intermediate precision (CV of 2.37-2.63%) and accuracy (90.7-94.3%) with adequate sensitivity for drug monitoring in bovine milk samples.

Animals↗

Continuous flow molecular emission cavity analysis of cephalosporins by alkaline degradation to sulphide.

A continuous flow method for the determination of some cephalosporins (cephradine, cephalexin, cephalosporin C, cefadroxil, cephapirin and cephalothin) in the general range 10.0-250.0 micrograms ml-1 is described. The sample is mixed with sodium hydroxide and remains for 20 min at 90 degrees C in the delay coil of an air-segmented system. The solution is then mixed with an excess of orthophosphoric acid, and the hydrogen sulphide evolved is continuously transferred into the cavity for generation of the S2 molecular emission. The analysis is automated, requires no sample pre-treatment and samples can be analysed at a rate of 30 per hour with a relative error of 1-2%. The method was evaluated by carrying out recovery experiments and by the analysis of commercial formulations. Results agreed well with those obtained by the standard methods.

Alkalies↗

Interspecies allometric analysis of the comparative pharmacokinetics of 44 drugs across veterinary and laboratory animal species.

The purpose of this study was to apply the method of allometric analysis to a study of the comparative disposition of veterinary drugs using the Food Animal Residue Avoidance Databank (FARAD) as a source of the comparative pharmacokinetic data. An initial filtration of the FARAD data was performed in order to exclude drugs for which no pharmacokinetic data were available, in at least four species the route of administration was other than intravenous, and the matrix was different from blood, plasma or serum. This process restricted the study to a total of 44 candidate drugs. The primary pharmacokinetic parameter selected for study was half-life (t1/2). As this parameter is a composite of clearance (Cl) and volume of distribution (Vd), it was considered to be the most robust for interspecies scaling. Volume of distribution at steady state (Vdss) and clearance showed weak allometric correlations with weight across species. The relationships between body weight and elimination half-life (51/2 beta) were determined for this selected group of drugs by using the empirically determined function Y = a Wb. The function Y represents the parameter of concern (half-life), a is a coefficient typical of every drug (intercept), W is the species average body weight, and b is the scaling exponent. A total of 11 drugs (tetracycline, oxytetracycline, chlortetracycline, erythromycin, diazepam, prednisolone, cephapirin, ampicillin, gentamicin, apramycin and carbenicillin) showed statistically significant correlations and consequently are excellent candidates for interspecies extrapolation of pharmacokinetic parameters (half-life) in species of relevance to veterinary medicine. The remaining 33 drugs were divided into two groups which showed various degrees of lack of correlation. Many of the drugs that showed no allometric correlation were low hepatic extraction drugs. However, some other drugs demonstrated equivocal results which could either be due to a true lack of allometric correlation, or be inconclusive due to the lack of quality data or excessive variability due to the multi-laboratory origin of the FARAD data. The results of this study show that interspecies scaling is applicable to certain veterinary drugs. The experimental determination of the coefficients of the allometric equation for relevant pharmacokinetic parameters (clearance and volume of distribution) could be an important tool in estimating dose in species where the drug has never been studied. This could have important consequences in terms of avoiding the use of dose-titration studies in Phase I of drug development, for drugs that are experimentally 'well behaved.'

Animals↗

Disulphide bonds are a requirement for adsorption of cephalosporins on the red cell membrane.

The authors studied the behavior of red cells (RBCs), treated with 2-aminoethylisothiouronium bromide (AET), against 100 serums containing cephalothin antibodies and 27 serums with cephapirin antibodies. None of the serums reacted with cephalosporin-coated RBCs that had been exposed previously to AET. The possibility of the Kell system acting as a receptor for cephalosporins was excluded. The authors discuss the significance of cysteine disulphide bonds and the tertiary or quaternary structure of red cell membrane proteins in the binding of cephalosporins to RBCs.

Adsorption↗

Susceptibility of "enterobacteria" to penicillins, cephalosporins, lincomycins, erythromycin, and rifampin.

Agar dilution tests for susceptibility of gram-negative rods and enterococci were done with a number of penicillins, cephalosporins, lincomycin analogues, erythromycin, and rifampin. Many in the first three categories were investigational drugs. All were generally less active than aminoglycoside and tetracycline antibiotics against gram-negative rods and more active against enterococci. Cephalosporins as a group were more active than penicillins against Klebsiella pneumoniae and Escherichia coli and less active enterococci. Both groups were equally active against Enterobacter, Proteus, and Providencia but inactive against most strains of Serratia and all strains of Pseudomonas; however, ticarcillin, carbenicillin, and BL-1654 were active against most strains of Pseudomonas. Penicillins and cephalosporins were more active against Proteus mirabilis than against indole-positive Proteus. Lincomycins had little or no activity against gram-negative rods but were moderately active against enterococci. Erythromycin was more active than the lincomycins, but rifampin was much more active than either of these types of drug. Of the penicillins, ticarcillin, carbenicillin, and BL-P1654 were the most active against gram-negative rods, whereas BL-P1654, amoxicillin, and ampicillin were the most active against enterococci. The penicillinase-resistant penicillins, cyclacillin, and penicillin V were essentially inactive against gram-negative rods. Of the cephalosporins tested, cephanone and cefamandole were the most active against most gram-negative rods, whereas cephaloridine and cephacetrile were the most active against enterococci. The least active of the cephalosporins against most species were cephradine, cephalexin, and cephapirin, but cefoxitin was the least active against enterococci.

Acinetobacter↗