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The specific activity, substrate profile, response to inhibitors, inducibility, and cellular localization of the beta-lactamase produced by an ampicillin-resistant strain of Haemophilus influenzae type B were investigated. In these properties the enzyme resembles beta-lactamases produced by other gram-negative bacilli more closely than those produced by gram-positive organisms. It is quite similar to an enzyme found in strains of Klebsiella pneumoniae, and differs significantly from those described in other gram-negative bacilli. Comparison of the substrate profile with the minimal inhibitory concentrations of various beta-lactamase antibiotics suggests that the beta-lactamase plays an important role in the antibiotic resistance of this organism.

A strain of Chromobacterium violaceum isolated from a fatally infected patient was found to produce a beta-lactamase. When the organism was grown in drug-free medium, beta-lactamase activity was barely detectable, but when it was grown in the presence of penicillin G, a much larger amount of activity was produced. The beta lactamase was active primarily against cephalosporins; it was sensitive to inhibition by cloxacillin but resistant to p-chloromercuribenzoate. Thus this enzyme closely resembled the common type of beta-lactamase found in Pseudomonas aeruginosa. The organism was relatively susceptible to ticarcillin, carbenicillin, and cefoxitin, which resected hydrolysis by its beta-lactamase, but was quite resistant to 11 other beta-lactam antibiotics. Production of the beta-lactamase appeared to be mediated by chromosomal genes.

Strains of Serratia marcescens fall into one of two groups with respect to their resistance to to beta-lactum antibiotics. Most strains are highly resistant to cephalosporins but are significantly more susceptible to ampicillin and carbenicillin, whereas other strains are highly resistant to both penicillins and cephalosporins. Strains in the former category produce small amounts of an inducible cephalosporinase, which appears to be chromosomally mediated. Strains in the latter class also elaborate large amounts of a noninducible penicillinase-cephalosporinase, which is plasmidmediated. Ability to produce this type of enzyme can be transferred to Klebsiella pneumoniae or Escherichia coli and may be lost spontaneously or after exposure of S. marcescens to "curing" agents.

Three newer cephalosporins (cefamandole, cefoxitin and cefazaflur) were investigated, in comparison with three older agents (cephalothin, cephaloridine and cefazolin) to determine their stability to beta-lactamases of gram-negative bacilli, and to correlate this with their antibacterial activity. Nine of the 17 bacterial strains employed produced broadspectrum beta-lactamases; the remaining eight produced cephalosporinases. The cephalosporins were highly active against bacteria producing broad-spectrum beta-lactamases; they were less active against organisms producing cephalosporinases. All of the cephalosporinase-producing strains were resistant to cephalothin anc cephaloridine. With the other cephalosporins the correlation between hydrolysis by cephalosporinases and resistance of the organisms was poor. Four to eight cephalosporinase-producing strains were resistant to cefoxitin, which was completely resistant to hydrolysis by the beta-lactamases. Cefozolin, cefamandole and cefazaflur inhibited several of these strains in spite of destruction by the beta-lactamase. Several cephalosporins need to be used in antimicrobial susceptibility testing of gram-negative bacilli.

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.

A new scheme for identification of coagulase-negative staphylococci was applied to 138 consecutive urinary isolates of coagulase-negative staphylococci. The most common species were Staphylococcus epidermidis (53%), S. hominis (12%), and S. haemolyticus (10%). S. saprophyticus comprised only 5%. The disk method for antibiotic susceptibility for all species grouped together disclosed resistance most commonly to penicillin (35%), tetracycline (33%), methicillin (27%), and sulfonamide (24%). This pattern was also seen specifically with S. epidermidis. Further studies are needed to determine the incidence of species-specific antibiotic resistance and species-specific infection by site. This may be of particular interest in those patients with nosocomial infections due to coagulase-negative staphylococci.