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[Comparison of two antimicrobial prophylaxis regimens in biliary tract surgery: a randomized controlled clinical trial].

OBJECTIVE: The aim of this study was to analyze the efficacy in prophylaxis during biliary tract and gallbladder surgery with amoxicillin/clavulanate and to compare it with the combination of cephalothin and clindamycin. DESIGN: A randomized nonblinded clinical trial with a blind independent observer. PLACE: Tertiary-care center. PATIENTS: Forty-two patients were included. All had undergone biliary tract and/or gallbladder surgery. They were divided in two groups: 22 in group A (cephalothin and clindamycin), and 20 in group B (amoxicillin/clavulanate). INTERVENTIONS: Patients from group A were intravenously treated with three doses of cephalothin (2 g at anesthetic induction and two additional doses of 1 g at six-hour intervals), and three of clindamycin (600 mg every six hours). Patients from group B received three doses of amoxicillin/clavulanate (1000/200 mg IV, one during the induction of the anesthesia followed by two more at six-hour intervals). RESULTS: In group A six wound infections were recorded, one of them with secondary bacteremia. In group B we did not record any infection (Fisher p < 0.01). One case of phlebitis was recorded in each group. CONCLUSIONS: Our results indicate that amoxicillin/clavulanate is useful in the prophylaxis of gallbladder and biliary tract surgery, and more effective than the combination of cephalothin and clindamycin.

Adult↗
PubMed2001

Postpneumonic empyema in childhood.

Fifty-six patients with postpneumonic empyema were treated by sulbactam/ampicillin or cephalothin and netilmicin. Dose of sulbactam/ampicillin was 200 mg/kg per day and of cephalothin was 200 mg/kg per day, and of netilmicin was 5 mg/kg per day. Sulbactam/ampicillin alone was used in 27 patients. Twenty-nine patients were treated with cephalothin plus netilmicin. Days on intravenous antibiotics, days with chest tube, decortication rate, and duration of hospitalization were significantly shorter in sulbactam/ampicillin treatment group compared to cephalothin plus netilmicin group. This study shows that sulbactam/ampicillin is a safe and effective agent in the treatment of postpneumonic empyema in childhood.

Anti-Bacterial Agents↗
PubMed1985

Investigation into the immunologic cross-reactivity of aztreonam with other beta-lactam antibiotics.

The cross-reactivity between the monobactam antibiotic aztreonam and the commonly used beta-lactam antibiotics, penicillins, and cephalosporins was investigated. Antibodies to aztreonam, penicillin, and cephalothin were raised in rabbits. The ability of the homologous or heterologous drug or drug conjugates to inhibit antibody binding was assessed in a solid-phase radioimmunoassay. Aztreonam demonstrated very little ability to interact with anti-penicillin or anti-cephalothin antibodies as it required 10,000-fold higher concentrations than other beta-lactams to achieve equivalent blocking. Similarly, penicillin and cephalothin conjugates did not cross-react, to any significant degree, with anti-aztreonam rabbit antiserums. Interestingly, free aztreonam was as effective as conjugated aztreonam in reacting with antibodies raised against conjugated aztreonam. This result suggested that, in contrast to the other beta-lactams, antibodies to aztreonam recognize the side chain rather than the nuclear structures. Studies with other beta-lactam analogs confirmed that the IgG rabbit anti-aztreonam binding was indeed side chain-specific. Thirty-six volunteers were given a seven-day course of therapeutic doses of aztreonam and in none did any detectable IgE anti-aztreonam antibodies develop. Four of these subjects had evidence of preexisting IgG antibodies cross-reactive with aztreonam, but the levels rose in only one patient following drug exposure. This human IgG anti-aztreonam was also directed to the side chain and did not cross-react with cephalothin or penicillin. The ability of aztreonam to cross-react with human IgE to various penicillin determinants was also investigated. Aztreonam determinants analogous to the penicillin determinants (penicillin, penicilloyl, and penicilloate) were constructed and the maximal concentration that did not evoke false-positive skin test results was determined to be 6 X 10(-3) mol/liter. None of 41 patients with documented IgE-reactive skin tests to various penicillin determinants concurrently demonstrated reproducible reactivity to any aztreonam reagents. IgE anti-penicilloyl antibodies from three persons were also tested in vitro for their ability to cross-react with conjugated or free aztreonam. Minimal, if any, reactivity was observed between the IgE anti-penicilloyl and any of the aztreonam materials. These results indicate that there is very little cross-reactivity between the monobactam aztreonam and other beta-lactam antibiotics.

Adult↗
PubMed1980

Antagonism of cefamandole by cefoxitin in routine disk susceptibility tests.

Cefoxitin was found to antagonize cefamandole in standardized disk diffusion susceptibility tests. This antagonism increased as the distance between the two disks decreased, and was most frequently observed in tests with cephalothin-resistant Enterobacteriaceae. It occurred in tests with 68 of 98 (69%) cephalothin-resistant isolates, one of six (17%) cephalothin-intermediate isolates, and one of 40 (3%) cephalothin-susceptible isolates. Clinical laboratories that use both disks in routine susceptibility tests should be aware of this anatagonism and should ensure that the disks are not placed in proximity to each other.

Cefamandole↗
PubMed1978

In vitro activity of cephalosporins against methicillin-resistant, coagulase-negative staphylococci.

The in vitro activity of five cephalosporins, gentamicin, and vancomycin was determined against 41 clinical isolates of methicillin-resistant, coagulase-negative staphylococci. Results obtained with disk diffusion and agar dilution methods failed to show complete cross-resistance between methicillin and four of the five cephalosporins despite the use of a high-salt medium and a large inoculum. Thirty-six (88%) of the 41 isolates were sensitive to cephalothin by a standardized disk diffusion method, whereas 23 isolates (56%) were sensitive to cephalothin with use of an agar dilution method and a large inoculum. Of these 23 isolates, only 11 (47%) were both inhibited and killed by less than or equal to 6.25 microgram of cephalothin/ml. The inhibitory and bactericidal activity of gentamicin was greater than that of vancomycin and cephalothin. These results suggest that the disk diffusion technique has limitations in determining the in vitro activity of cephalosporins against methicillin-resistant, coagulase-negative staphylococci and that cephalothin exhibits poor bactericidal activity against these same isolates.

Cephalosporins↗
PubMed1978

Comparative beta-lactamase resistance and antistaphylococcal activities of parenterally and orally administered cephalosporins.

Two parenterally administered cephalosporins (cephalothin and cephapirin) and four orally administered cephalosporins (cephalexin, cephradine, cefatrizine, and cefaclor) were investigated by use of 29 beta-lactamase-producing strains of Staphylococcus aureus for determination of their relative rates of hydrolysis (RH) by beta-lactamase (RH of penicillin G =100) and their antistaphylococcal activities. Cephalothin (RH less than 0.01) and cephapirin (RH = 0.1) were relatively stable in the presence of staphylococcal beta-lactamase. Cephalexin and cephradine (RH of each = 0.3) were less stable than cephalothin and cephapirin but more stable than cefatrizine (RH = 1.4) and cefaclor (RH = 3.4). Agents that were more resistant to hydrolysis were affected less by the size of the inoculum when tested against large ;(10(7)) and small (10(3)) inocula of beta-lactamase-producing staphylococci than those that were hydrolyzed rapidly. Cephalothin and cephapirin were four to eight times more active than the orally administered cephalosporins against 10(3) staphylococci. Cephalosporins that are relatively stable in the presence of staphylococcal bata-lactamase may be preferable to less stable ones for treatment of serious infections due to beta-lactamase-producing staphylococci.

Administration, Oral↗
PubMed1991

Potentiation of murine cytomegalovirus pneumonitis by antibiotics in clinical use.

Nineteen antibiotics were screened for their effects on the proliferation of murine spleen cells in vitro. Ketoconazole suppressed lymphoproliferation at clinically-attainable concentrations, whilst tetracycline, cephalothin, rifampicin and ciprofloxacin were also inhibitory at relatively low concentrations. These antibiotics were selected for further study. High concentrations of cephalothin inhibited macrophage uptake of colloidal gold, while spleen cells from mice treated with ketoconazole responded poorly to mitogenic stimulation in vitro. Humoral responses to ovalbumin, polyvinylpyrrolidone and murine cytomegalovirus (MCMV) were not suppressed by oral administration of ketoconazole, tetracycline, cephalothin, rifampicin or ciprofloxacin to mice. However, MCMV-infected mice receiving these antibiotics had increased virus loads and a greater persistence of virus and interstitial pneumonitis in their lungs. This was observed with clinically-attainable serum concentrations of cephalothin, tetracycline and ciprofloxacin. The findings warrant further investigation as the antibiotics are used to control secondary infections in immunosuppressed patients, many of whom experience cytomegalovirus disease.

Animals↗
PubMed1993

The accumulation of five antibacterial agents in porin-deficient mutants of Escherichia coli.

A library of isogenic mutants containing Mud9-induced deletions of the structural and regulatory genes for the porin proteins OmpF and OmpC of Escherichia coli was constructed. The accumulation of norfloxacin, tetracycline, chloramphenicol, cephalothin and cefoxitin was measured with each strain, and shown to be reproducible with low experimental standard deviations, such that the roles of OmpF, OmpC and PhoE in the accumulation of these agents were determined. All data were statistically analysed to determine whether the differences observed between the data for each mutant compared with those for the other mutants and for the wild-type strain were significant. The loss of OmpF reduced accumulation of norfloxacin, tetracycline, cephalothin and cefoxitin by 16-60% compared to the wild-type parent strain, but reduced accumulation of chloramphenicol by < 10%. The loss of OmpC reduced accumulation of cephalothin and cefoxitin by 13 and 34%, respectively, compared to the wild-type parent strain, but had little effect on the accumulation of norfloxacin, chloramphenicol and tetracycline (< 3%). The loss of both OmpF and OmpC (ompR) reduced accumulation of norfloxacin, chloramphenicol, tetracycline, cephalothin and cefoxitin by 36-68%. However, the presence of PhoE in the absence of both OmpF and OmpC, enhanced accumulation to 52-119% of the concentrations of these five agents accumulated by the wild-type strain. These data suggest that OmpF is the preferred route of entry for three of the antibiotics studied, but not for chloramphenicol and tetracycline which utilize both porins equally well. The high levels of accumulation (30-64%) of all five antibiotics in the absence of all major porins suggest that an alternative mechanism(s) of accumulation is available.

Anti-Infective Agents↗
PubMed1998

Emergence of penicillin-resistant Streptococcus pneumoniae ocular infections.

BACKGROUND: Approximately 15-20% of Streptococcus pneumoniae clinical isolates in the United States are not susceptible to penicillin. Isolates with a minimum inhibitory concentration (MIC) of 0.12-1.0 mg/ml are intermediately resistant, and those with an MIC > 2.0 microg/ml are classified as having high-level penicillin resistance. PURPOSE: We determined the proportion of penicillin-resistant S. pneumoniae recovered from ocular and periocular infections from 1976 through 1995, compared these cases with penicillin-susceptible controls, and evaluated the susceptibility of penicillin-resistant isolates to selected cephalosporins and fluoroquinolones. METHODS: MICs for cephalothin, ceftazidime, ciprofloxacin, and ofloxacin were determined for available isolates by the E test. We performed a case-comparison study to evaluate differences between patients with penicillin-susceptible and -nonsusceptible ocular pneumococcal infections. RESULTS: Of 173 ocular isolates of S. pneumoniae isolated in the 20-year period, 12 (7%) were not susceptible to penicillin, including eight (5%) intermediate isolates and four (2%) highly resistant isolates. Penicillin-intermediate and -resistant pneumococci were recovered at a rate of none of 46 isolates from 1976 through 1980, one (4%) of 25 from 1981 through 1985, one (2%) of 51 from 1986 through 1990, and 10 (20%) of 51 from 1991 through 1995 (p < 0.0004). We found no significant differences in presenting characteristics between patients with ocular infections due to penicillin-susceptible pneumococci and those caused by nonsusceptible strains. All retested isolates with intermediate susceptibility to penicillin had a cephalothin MIC < or = 1.5 microg/ml, and all retested isolates with high-level penicillin resistance had a cephalothin MIC > or = 4 microg/ml. The ceftazidime MIC for all penicillin-resistant isolates was > or = 24 microg/ml. All penicillin-nonsusceptible isolates had MICs < or = 1.5 microg/ml for ciprofloxacin and < or = 3 microg/ml for ofloxacin. CONCLUSION: Penicillin resistance has recently emerged among ocular S. pneumoniae. Cephalothin, ciprofloxacin, and ofloxacin have good activity against some ocular isolates with intermediate penicillin susceptibility, although another agent such as vancomycin may be needed for pneumococci with high-level penicillin-resistance.

Adolescent↗
PubMed1983

Population analysis of susceptibility to methicillin, vancomycin, and three cephalosporines in two methicillin-resistant strains of Staphylococcus epidermidis.

Population analyses of susceptibility to methicillin, vancomycin, cephalothin, cefamandole, and cefoxitin were carried out with two strains of Staphylococcus epidermidis (S. epidermidis) resistant to penicillin, streptomycin, and methicillin. Two strains of Staphylococcus aureus (S. aureus), one sensitive to penicillin the other resistant, were used as controls. All strains were clinical isolates. From the strains of S. epidermidis it was possible to select sub-populations highly resistant to methicillin, cephalothin, cefamandole, and cefoxitin. The mutation-rate varied between c. 10(-3) and 10(-7). The two strains were homogeneous as regards vancomycin susceptibility. Methicillin was shown to be more penicillinase-stable than the cephalosporines. Treatment in vivo, with cephalothin and vancomycin did not increase the frequency of highly resistant bacteria against any of the antibiotics, but during treatment with cephalothin the majority-population became eight times more resistant to vancomycin and may explain why the treatment in vivo was not successful.

Cephalosporins↗
PubMed1977

In vitro studies with cefaclor, a new oral cephalosporin.

In vitro studies were performed to evaluate the activity of cefaclor in comparison with cephalexin against 180 clinical isolates. Broth dilution susceptibility tests showed cefaclor to be 4- to 16-fold more active than cephalexin against Streptococcus pneumoniae, Haemophilus influenzae, and cephalothin-susceptible Enterobacteriaceae. Neither drug was highly active against cephalothin-resistant Enterobacteriaceae or methicillin-resistant Staphylococcus aureus. Cefaclor zones with 30-mug disks were generally larger than cephalexin zones, 4 mm larger than cephalothin zones against Enterobacteriaceae, and 6 mm smaller than cephalothin zones against S. aureus. Quantitative kill curves indicated that killing by both cefaclor and cephalexin was slow and often incomplete over a 24-h period. Cefaclor-induced filamentation of gram-negative bacilli was not as extensive as that produced by cephalexin, and some spherule formation did occur. However, cefaclor was significantly more unstable in solution than cephalexin, with a half-life of less than 6 h at 37 degrees C. Thus, results obtained in tests after prolonged incubation may not provide an accurate measure of cefaclor's activity.

Bacteria↗
PubMed1978

Ascitic fluid cephalosporin concentrations: influence of protein binding and serum pharmacokinetics.

Mongrel dogs with ascites created by inferior vena cava ligation were given cephalothin, cephaloridine, cefazolin, and cefamandole to evaluate the effect of protein binding and serum pharmacokinetics on the distribution of cephalosporins into ascitic fluid. Antibiotics were given intramuscularly (15 mg/kg) every 4 h for a total of eight doses. Antibiotic binding to dog serum and ascitic fluid was measured by ultracentrifugation. Binding of the cephalosporins to dog serum ranged from 31% for cephaloridine to 46% for cephalothin, considerably lower than human serum binding for cefazolin, cephalothin, and cefamandole. Antibiotic binding to ascitic fluid was only slightly lower than that to serum. Ascitic fluid antibiotic concentrations, which approached equilibrium at 16 to 28 h, were significantly higher for cefazolin and cephaloridine than for cephalothin and cefamandole. However, serum concentrations were also higher for cefazolin and cephaloridine, and percent penetration (ratio of serum peak to ascites peak x 100) was not statistically different among the four drugs. Binding of these cephalosporins to extravascular fluid protein was an important factor that determined the total ascitic fluid antibiotic level achieved. A formula utilizing the log mean serum level and binding to serum and extravascular fluid protein was used to accurately predict ascitic fluid drug levels at equilibrium.

Animals↗
PubMed1978

Antimicrobial susceptibility and selection of resistance among Staphylococcus epidermidis isolates recovered from patients with infections of indwelling foreign devices.

Twenty-seven isolates of Staphylococcus epidermidis from patients with prosthetic valve endocarditis or infected cerebrospinal fluid shunts were examined for susceptibility to antimicrobial agents. Subpopulations resistant to 20 and 100 mug of methicillin per ml were present in 63% of the isolates (methicillin-resistant isolates). Subpopulations resistant to 20 mug of nafcillin and cephalothin per ml were found in every methicillin-resistant isolate but with frequencies (10(-5.0 +/- 0.5) and 10(-6.4 +/- 0.9), respectively) which were not always detectable by susceptibility testing. Resistance to >/=1.6 mug of penicillin per ml was found in 80% of isolates. Cephalothin, cefazolin, and cefamandole were more active than cefoxitin or cephradine, and gentamicin was more active than tobramycin or amikacin; rifampin was the single most active agent against all isolates. There was no difference in susceptibility between prosthetic valve endocarditis and cerebrospinal fluid shunt infection isolates. Among methicillin-resistant isolates, the phenotypic expression of resistance to methicillin or nafcillin but not to cephalothin could be enhanced by 48 h of incubation with each drug. Isolates containing no methicillin-resistant subpopulations were killed by incubation with methicillin, nafcillin, or cephalothin. High-level resistance to rifampin emerged in both methicillin-resistant and methicillin-sensitive isolates after 8 to 24 h of incubation with this drug. The presence or absence of antibiotic-resistant subpopulations among S. epidermidis isolates and their selection during treatment should be considered when therapy is devised.

Anti-Bacterial Agents↗
PubMed1980

Antibiotic therapy of experimental Staphylococcus epidermidis endocarditis.

Endocarditis was produced in rabbits with a methicillin-resistant Staphylococcus epidermidis isolate. Subpopulations resistant to other semisynthetic penicillins and cephalosporins were detected in the isolate. Their presence was probably responsible for the increase in minimum bactericidal concentrations and minimum inhibitory concentrations when tests with high inocula, rather than low inocula were pursued. Rabbits were treated for either 2 or 7 days with nafcillin, cephalothin, cefamandole, vancomycin, rifampin, or gentamicin. Spontaneous death was uncommon in either controls (84% survival) or treated animals (80 to 94% survival). There was no significant difference in the number of bacteria in vegetations of rabbits treated for 7 days with cephalothin, cefamandole, nafcillin, or no antibiotic (control). There was a significant reduction in total bacteria in vegetations of rabbits given vancomycin, gentamicin, or rifampin for 7 days as compared with cephalothin, cefamandole, nafcillin or control. Gentamicin or rifampin sterilized significantly more vegetations after 7 days than cephalothin, cefamandole, nafcillin, or control; rifampin was more effective in sterilizing vegetations than either gentamycin or vancomycin after 2 days. Mutants resistant to 10 mug of rifampin per ml comprised the total bacterial population cultured from vegetations of 2 of 17 rabbits treated with this antibiotic for 7 days; there was no change in the susceptibility of vegetation isolates to other antibiotics. Rifampin, vancomycin, or gentamicin may prove to be more effective in humans than cephalosporins or semisynthetic penicillins in the treatment of methicillin-resistant S. epidermidis endocarditis.

Animals↗
PubMed1980

Activity of ten cephalosporins on biomass of methicillin-susceptible and -resistant Staphylococcus aureus.

The growth curves automatically recorded and printed during the action of 10 cephalosporins on methicillin-susceptible and methicillin-resistant Staphylococcus aureus showed the following. (i) The biomass of methicillin-susceptible S. aureus exposed to the cephalosporins increased before lysis occurred (inoculum, 10(6) colony-forming units per ml). Lysis was more rapid with cephalothin and cephaloridine, whose minimal inhibitory concentrations were lowest. (ii) The same biomass increase followed by lysis occurred with methicillin-resistant S. aureus, and the speed of lysis was not different from those of cephalothin (without any regrowth), cefoxitin (with regrowth of a few strains), and cephaloridine (regrowth of all strains), with methicillin-susceptible strains. A 2-log increase of inoculum (10(8) colony-forming units per ml) did not modify significantly the speed of lysis with cephalothin, cephaloridine, and cefoxitin, but regrowth sometimes occurred. The early transitory lysis caused by cephaloridine, cephalothin, cefamandole, and cefoxitin was not suppressed by preincubation with 32 mug of methicillin per ml, but regrowth occurred more frequently. No lysis could be observed with cefazolin, cefotaxime, cephalexin, cephradine, cefuroxime, and cefaclor unless high concentrations were achieved. (iii) From a practical point of view, the early response of the growth curve (4 h) could not determine in every case whether a strain of S. aureus was resistant or susceptible to cephalosporin. A further study of the growth curve (18 of 24 h) was necessary for this purpose. Results obtained after a few hours with automated systems should be interpreted with great caution.

Cephalosporins↗
PubMed1980

Effect of storage and changes in bacterial growth phase and antibiotic concentrations on antimicrobial tolerance in Staphylococcus aureus.

Forty clinical isolates of Staphylococcus aureus were tested for tolerance to oxacillin and cephalothin by broth dilution susceptibility tests and killing curves. Most experiments were carried out with stationary-phase inocula, but nine tolerant isolates were retested with log-phase inocula. All 40 isolates were retested in killing curves at double the antibiotic concentrations used in initial tests. Isolates were retested for tolerance to oxacillin after storage at --70 degrees C for 1 year. In broth dilution tests, 23 of 40 (57.5%) and 20 of 40 (50%) isolates were tolerant to oxacillin and cephalothin, respectively. By killing curves, 25 of 40 (62.5%) and 22 of 40 (55%) isolates were tolerant to oxacillin and cephalothin, respectively. When nine tolerant isolates were retested with log-phase inocula, none manifested tolerance. Only 25 to 30% of the isolates were tolerant in killing curves performed with oxacillin and cephalothin at concentrations double those used in initial tests. After storage at --70 degrees C for 1 year, only two-thirds of the isolates remained tolerant. In isolates that remained tolerant, the degree of tolerance diminished to about 25% of that observed in initial tests.

Anti-Bacterial Agents↗
PubMed1972

Cephamycins, a new family of beta-lactam antibiotics. 3. In vitro studies.

Cephamycins A, B, and C are naturally produced cephalosporin-type antibiotics. Although A and B were found to be more active than C against gram-positive organisms, they were not so active against such strains as are cephalosporin C or the semisynthetic antibiotics cephaloridine and cephalothin. Against gram-negative organisms, cephamycin C was more active than A or B and, in general, was as active as the cephalosporins. In addition, cephamycin C was active in vitro against clinically isolated strains resistant to the cephalosporins, such as Proteus, Providencia, and Escherichia coli. The in vitro antibacterial activity of cephamycin C, cephalothin, and cephaloridine is primarily bactericidal. A 10,000-fold increase in inoculum of a strain of Proteus mirabilis resulted in 200-fold or greater increases in minimal inhibitory and minimal bactericidal end points of cephalothin and cephaloridine, but only 10- and 16-fold increases, respectively, for cephamycin C. After 15 passages through antibiotic-containing broths, during which time a culture of E. coli showed an increase in minimal inhibitory concentrations of streptomycin of >1,000-fold, end points for cephamycin C increased 4-fold, for cephalothin, 1.5-to 6-fold, and for cephaloridine, 128-fold.

Bacteria↗
PubMed1986

In vivo target of benzylpenicillin in Gaffkya homari.

It has been established that the DD-carboxypeptidase is the primary in vitro target of benzylpenicillin in Gaffkya homari (W. P. Hammes, Eur. J. Biochem. 70:107-113, 1976). To determine whether this enzyme is also the primary target of benzylpenicillin in vivo, we compared the effects of this beta-lactam, cefmenoxime, cephalothin, and cefoxitin on growth with their acylation of penicillin-binding protein (PBP) 9, the DD-carboxypeptidase. Results of three types of experiments with membrane-walls indicated that PBP 9 is this enzyme and that it is the primary in vitro target of these beta-lactams in the synthesis of sodium dodecyl sulfate (SDS)-insoluble peptidoglycan. First, the acylation of PBP 9 by these beta-lactams paralleled the inhibition of DD-carboxypeptidase and the inhibition of SDS-insoluble peptidoglycan synthesis. Second, the rate of benzylpenicillin release from PBP 9 correlated with the recovery of DD-carboxypeptidase. Third, DD-carboxypeptidase activity was detected in a protein with the same apparent molecular weight as PBP 9 after elution from an SDS-polyacrylamide gel. When intact cells were treated with benzylpenicillin, the minimum growth inhibitory concentration (MGIC) correlated with the concentration of [35S]benzylpenicillin required to acylate PBPs 6 and 9 by 50%. When intact cells were treated with cefmenoxime, cephalothin, or cefoxitin, the MGICs correlated with the concentration of unlabeled beta-lactam required to reduce the subsequent binding of [35S]benzylpenicillin by 50% (ED50) for PBP 6. In contrast, the MGICs of these beta-lactams did not correlate with the ED50s for PBP 9. PBP 9 was not acylated by cefmenoxime or cephalothin at their MGICs, whereas this PBP was fully acylated by cefoxitin at one-tenth of its MGIC. It is suggested that PBP 6 may be a primary target of growth inhibition by benzylpenicillin, cefmenoxime, cephalothin, and cefoxitin; PBP 9, the DD-carboxypeptidase, is dispensable for growth under laboratory conditions; and PBP 9 does not appear to be a primary in vivo target of these beta-lactams, even though this PBP is their primary target in vitro.

Bacterial Proteins↗