Showing papers on "Penicillin published in 1978"

Emergence of multiply resistant pneumococci.

Abstract: Multiple antimicrobial resistance in pneumococci was detected in Johannesburg in July, 1977, and prompted an investigation of the prevalence of resistant strains in two hospitals. Carriers of Types 6A and 19A penicillin-resistant pneumococci, resistant to antibiotic concentrations ranging between 0.12 and 4 microgram per milliliter were found in 29 per cent of 543 pediatric patients and 2 per cent of 434 hospital staff members. Multiply resistant Type 19A strains, resistant to beta-lactam antibiotics, erythromycin, clindamycin, tetracycline and chloramphenicol, were isolated from 128 carriers, and were responsible for bacteremia in four patients. Isolates from 40 other carriers were resistant to penicillin alone or to penicillin and chloramphenicol or to penicillin, chloramphenicol and tetracycline. Pneumococci can be screened for penicillin resistance with a modified Kirby--Bauer technic; the strains with zones of less than 35 mm around 6-microgram penicillin disks or less than 25 mm around 5-microgram methicillin disks should be tested for sensitivity to penicillin by measurements of minimum inhibitory concentration.

Antimicrobial Susceptibility and Selection of Resistance Among Staphylococcus epidermidis Isolates Recovered from Patients with Infections of Indwelling Foreign Devices

Abstract: 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(-50 +/- 05) and 10(-64 +/- 09), respectively) which were not always detectable by susceptibility testing Resistance to >/=16 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

Piperacillin, a new penicillin active against many bacteria resistant to other penicillins.

Abstract: The in vitro activity of piperacillin, a new semisynthetic piperazine penicillin derivative, was evaluated against 626 clinical isolates and compared with the activity of other beta-lactam antibiotics. At a concentration of 0.1 microgram/ml, piperacillin inhibited all streptococci except enterococci. Non-beta-lactamase-producing staphylococci were inhibited by 1.6 microgram or less per ml. Both beta-lactamase- and non-beta-lactamase-producing Haemophilus were inhibited by 0.1 microgram/ml. Piperacillin inhibited non-beta-lactamase-producing Escherichia coli, Salmonella, and Shigella at a concentration of 6.3 micrograms/ml, but 20% of strains of these species containing type III beta-lactamase were not inhibited by 100 micrograms/ml. Piperacillin at 25 micrograms/ml, inhibited 83% of Citrobacter, 58% of Klebsiella, 88% of Enterobacter, and 50% of indole-positive Proteus, Acinetobacter, and Providencia. At 25 micrograms/ml, piperacillin inhibited 95% of Pseudomonas aeruginosa and 78% of Bacteroides fragilis. The minimal inhibitory concentration of piperacillin against Pseudomonas was affected by increasing the inoculum size and by pH. Minimum bactericidal concentrations against Pseudomonas and Serratia often were eightfold greater than the minimum inhibitory concentrations. Piperacillin was equal in activity to ampicillin against enterococci. It was more active than carbenicillin against E. coli, Klebsiella, Enterobacter, and Bacteroides. It was the most active penicillin against Pseudomonas and inhibited many strains of Pseudomonas for which the MICs of carbenicillin were above 200 micrograms/ml. Piperacillin was hydrolyzed by many different beta-lactamases. Synergistic activity of piperacillin was demonstrated when it was combined with amikacin, gentamicin, and cefazolin against P. aeruginosa and members of the Enterobacteriaceae. No antagonism was observed when piperacillin was combined with aminoglycosides; however, antagonism was observed rarely against E. coli when piperacillin was combined with cefazolin.

Immunologic Cross-Reactivity between Penicillins and Cephalosporins: A Review

Abstract: Several approaches have been undertaken in the study of possible immunologic cross-reactivity between cephalosporins and penicillins. Although the chemical structures of these compounds are similar in several respects, there are distinct differences in their degradation and transformation. Various degrees of cross-reactivity of antibodies produced in response to administration of these drugs have been demonstrated both with test systems that measure IgG and IgM antibodies and with those that measure IgE antibodies. The clinical significance of immune responses to cephalosporins is best understood in regard to immunohematologic abnormalities: positive direct antiglobulin (Coombs') tests occur in only approximately 3% of patients receiving cephalosporins; however, several cases of cephalosporin-induced immune hemolytic anemia have been reported. Clinical studies of the cephalosporins indicated that patients with a history of penicillin allergy have increased incidence of reactivity to cephalosporins, but it is impossible to determine to what extent this finding is due to immunologic cross-reactivity because penicillin-allergic patients have an increased incidence of hypersensitivity reactions to drugs immunologically unrelated to penicillins. In addition, there is evidence of specific immune response to cephalosporins that indicates independently acquired hypersensitivity rather than cross-reactivity in some patients.

Staphylococcus aureus endocarditis. Combined therapy with vancomycin and rifampin.

Abstract: Two children with persistent bacteremia and endocarditis due to Staphylococcus aureus failed to respond to vancomycin therapy, even though serum levels greatly exceeded the inhibitory concentrations. The Staphylococcus from one patient was resistant to methicillin; the other patient had a penicillin hypersensitivity. There was a wide disparity between the minimum inhibitory and the minimum bactericidal concentrations of vancomycin. Striking clinical and laboratory evidence of improvement was demonstrated with the addition of rifampin therapy. ( JAMA 240:1963-1965, 1978)

Excretion of lipoteichoic acid by group A streptococci. Influence of penicillin on excretion and loss of ability to adhere to human oral mucosal cells.

Abstract: Group A streptococci were grown in the presence of [2-3H]glycerol. Concentrated suspensions of the labeled organisms were incubated with and without penicillin. [3H]Glycerol-labeled material accumulated in the supernates in increasing amounts with increasing concentrations of penicillin, ranging from 0 to 50 U/ml. The excretion of labeled material occurred in the absence of nucleic acid synthesis or bacteriolysis indicating that the phenomenon is independent of cell multiplication or decay. The accumulation of label was paralleled by an accumulation of erythrocyte-sensitizing material measured by passive hemagglutination tests for lipoteichoic acid antigen, indicating that a portion of the labeled material possessed the properties of lipoteichoic acid. Culture supernates were fractionated by column chromatography, and the materials obtained were analyzed by electrophoresis on sodium dodecyl sulfate polyacrylamide, thin-layer chromatography, and paper chromatography. The ability of the same materials to bind to human erythrocytes and epithelial cells was tested. The culture supernate contained lipoteichoic acid, deacylated lipoteichoic acid, glycerol phosphate, and free glycerol. Penicillin caused an increase in the amounts of each of the excreted materials. Streptococci that were stimulated with penicillin to lose their lipoteichoic acid (previously shown to mediate adherence of group A streptococci) lost their ability to adhere to buccal mucosal cells, suggesting that penicillin may influence bacterial ecology by mechanisms other than killing sensitive organisms.

In vitro study of clavulanic acid in combination with penicillin, amoxycillin, and carbenicillin.

Abstract: The activity of clavulanic acid alone and in combination with penicillin, amoxycillin, and carbenicillin was studied. Marked reductions in the minimum inhibitory concentrations (MICs) for a wide spectrum of beta-lactamase-producing clinical isolates were found. Of particular interest were the decreased MICs of penicillin for Bacteroides fragilis and beta-lactamase-producing strains of Neisseria gonorrhoea in the presence of the clavulanic acid. Beta-lactamase-producing strains of Escherichia coli, Klebsiella spp., and indole-negative Proteus also showed considerably increased susceptibility to amoxycillin in combination with clavulanic acid. Two beta-lactamase-producing strains of Pseudomonas aeruginosa remained resistant to carbenicillin in the presence of clavulanic acid.

Aminoglycoside-Inactivating Enzymes in Clinical Isolates of Streptococcus Faecalis: AN EXPLANATION FOR RESISTANCE TO ANTIBIOTIC SYNERGISM

Abstract: Clinical isolates of enterococci (Streptococcus faecalis) with high-level resistance to both streptomycin and kanamycin (minimal inhibitory concentration >2,000 mug/ml), and resistant to synergism with penicillin and streptomycin or kanamycin were examined for aminoglycoside-inactivating enzymes. All of the 10 strains studied had streptomycin adenylyltransferase and neomycin phosphotransferase activities; the latter enzyme phosphorylated amikacin as well as its normal substrates, such as kanamycin. Substrate profiles of the neomycin phosphotransferase activity suggested that phosphorylation occurred at the 3'-hydroxyl position, i.e., aminoglycoside 3'-phosphotransferase. A transconjugant strain, which acquired high-level aminoglycoside resistance and resistance to antibiotic synergism after mating with a resistant clinical isolate, also acquired both enzyme activities. Quantitative phosphorylation of amikacin in vitro by a sonicate of the transconjugant strain inactivated the antibiotic, as measured by bioassay, and the phosphorylated drug failed to produce synergism when combined with penicillin against a strain sensitive to penicillin-amikacin synergism.No differences were found in the sensitivity of ribosomes from a sensitive and resistant strain when examined in vitro using polyuridylic acid directed [(14)C]-phenylalanine incorporation in the presence of streptomycin, kanamycin, or amikacin. Therefore, we conclude that aminoglycoside-inactivating enzymes are responsible for the aminoglycoside resistance, and resistance to antibiotic synergism observed in these strains.

Diagnosis of penicillin allergy by skin testing: the Manitoba experience

Abstract: The reliability of skin testing in the diagnosis of penicillin allergy was studied in 86 adults and 167 children with a history of possible hypersensitivity reactions to penicillin. Skin testing was done with the major antigenic determinant of benzylpenicillin and minor determinants of benzylpenicillin, ampicillin, cloxacillin, methicillin and cephalothin. The overall frequency of positive skin reactions was 11.5%. Among the patients with positive skin reactions about half had a history of immediate or accelerated reactions to penicillins, but 2 of 11 adults and 50% of the children in this group had a history of maculopapular rash of delayed onset. There was a low frequency of positive skin reactions when there was a long interval between the times of clinical reaction and skin testing. Of 169 patients reacting negatively to skin testing who received a specific drug challenge only 2 manifested mild urticaria; this indicates the reliability of the skin tests in predicting penicillin allergy. The major and minor determinants of benzylpenicillin were the most useful reagents. One fifth of the patients with penicillin hypersensitivity would have been missed if the major determinant of benzylpenicillin alone had been used for skin testing. The additional use of the minor determinants of other penicillin derivatives, however, did not increase substantially the clinical reliability of the skin testing procedure.

In vitro activity of antimicrobial agents on Legionnaires disease bacterium.

Abstract: Six isolates of Legionnaires disease bacteria were tested for their susceptibility to 22 antimicrobial agents. The most active agent was rifampin (minimal inhibitory concentration,

HR 756, a highly active cephalosporin: comparison with cefazolin and carbenicillin.

Abstract: HR 756, a new parenteral cephalosporin, was compared with cefazolin and carbenicillin for activity against a total of 264 strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus spp. (indole positive), Enterobacter spp., Salmonella typhi, Serratia marcescens, Providencia stuartii, and Staphylococcus aureus. In every comparison, except that with the last organism, HR 756 was clearly more active than cefazolin and carbenicillin. All three compounds had similar activity against penicillin-susceptible staphylococci; against penicillin-resistant strains, HR 756 and cefazolin were equally active and superior to carbenicillin. HR 756 was compared with penicillin for activity against strains of Streptococcus pyogenes, Lancefield group D streptococci, and Neisseria gonorrhoeae; with ampicillin against Haemophilus influenzae; and with cefoxitin against Bacteriodes fragilis. HR 756 was clearly more active than the respective reference compounds in all of these comparisons, except those involving the streptococci. HR 756 and penicillin were essentially equally active against S. pyogenes; against Lancefield group D, penicillin was 32 times as active as HR 756. HR 756 not only compared favorably with the reference compounds with respect to relative activity, but also effected growth inhibition of essentially all test organisms (P. aeruginosa and group D streptococci excepted) at remarkably low concentrations ranging from 0.015 to 2.0 μg/ml. A series of seven transfers of selected strains of E. coli, Klebsiella spp., S. aureus, and P. aeruginosa through medium containing HR 756 led to emergence of strains with significant levels of resistance to the agent. Resistance to HR 756 was retained for at least seven transfers through plain medium.

Pharmacologic evaluation of orally administered antibiotics in infants and children: Effect of feeding on bioavailability

Abstract: The clinical pharmacology of orally administered antibiotics was investigated in 106 infants and children. The antibiotic suspensions studied were ampicillin, cephalexin, erythromycin estolate, erythromycin ethylsuccinate, penicillin G, and penicillin V. The feeding status of the patients was evaluated in relation to the concentrations of drugs in serum, saliva, and tears. Peak concentrations and area-under-the-curve values of cephalexin, penicillin V, and penicillin G were reduced 40% to 60% in patients given milk and drug concurrently. Absorption was enhanced when erythromycin ethylsuccinate was given milk. After administration of both erythromycin formulations, penicillin V and ampicillin, salivary concentrations exceeded the minimal inhibitory concentrations for most pneumococci and group A streptococci and for many meningococci. The clinical implications of these pharmacokinetic data are discussed.

Susceptibility of Anaerobic Bacteria to Ten Antimicrobial Agents

Abstract: The susceptibility pattern of 265 anaerobic bacteria from clinical isolates to 10 antimicrobial agents was investigated by the agar dilution technique. Penicillin G, in a concentration of 16 μg/ml, was active against most organisms, important exceptions being 12% of Bacteroides melaninogenicus and 24% of B. fragilis strains. The susceptibility of strains to ampicillin was similar to their susceptibility to penicillin G. Carbenicillin, at ≤128 μg/ml, inhibited all but a few strains. Cefamandole was less active than the penicillins; 82% of B. melaninogenicus , 32% of B. fragilis , and 75% of Fusobacterium strains were inhibited by ≤16 μg/ml. A trend towards tetracycline resistance was seen in many bacterial groups, especially Bacteroides, Fusobacterium , and Clostridium . All organisms were susceptible to chloramphenicol and clindamycin in concentrations of ≤16 μg/ml and ≤4 μg/ml, respectively. Erythromycin was less active than clindamycin against all strains tested. Metronidazole and tinidazole were active against most anaerobes, but resistance of a few strains in each group was encountered. The increased resistance of B. melaninogenicus strains to penicillin, and emergence of anaerobes resistant to >16 μg of imidazole per ml may have therapeutic implications.

Species identification of coagulase-negative staphylococci from urinary tract isolates.

Abstract: 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.

Antibiotic susceptibility of clinical isolates of Listeria monocytogenes.

Abstract: A broth microdilution method was used to measure the minimal inhibitory concentrations (MICs) of the antibiotics most often recommended for treatment of listeriosis. The MICs of ampicillin, penicillin, erythromycin, and tetracycline for 175 strains of Listeria monocytogenes were below the approximate MIC breakpoint for susceptible strains as recommended by the National Committee on Clinical Laboratory Standards. Inhibition diameters for 125 strains were measured by the standardized disk method (National Committee on Clinical Laboratory Standards) and compared with the appropriate MIC values. By both methods, strains were susceptible to the above four antibiotics, except for three strains, which were intermediate in susceptibility to penicillin by the disk method. Since the minimal bactericidal concentrations for ampicillin and penicillin significantly exceeded the MICs for these antibiotics, 45 strains were evaluated with ampicillin (5 μg/ml) and gentamicin (1 μg/ml) to compare the synergistic bactericidal effect of the two used in combination and singly. An increased kill of 100-fold was observed with the antibiotics combined in 19 strains after 4 to 6 h and in 40 strains after 24 h. A comparison of results with microdilution in Trypticase soy broth and agar dilution in Mueller-Hinton agar revealed that MICs for gentamicin, kanamycin, and streptomycin were strongly influenced by the media used. The MICs were consistently lower in Mueller-Hinton agar.

Antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae. Report of a study group on bacterial resistance.

Abstract: Twenty laboratories in England and Scotland took part in 1977 in a survey of antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae. In Str pneumoniae 59 (6.8%) of the 866 strains studied were resistant to tetracycline and three to chloramphenicol, and one strain showed a decreased susceptibility to penicillin. The prevalence of resistance to tetracycline was lower than that found in a similar study performed in 1975. Nine hundred and fifty-two strains of H influenzae were examined: 15 (1.6%) were resistant to ampicillin (all were beta-lactamase producers) and 26 (2.7%) to tetracycline. Only two strains were resistant to chloramphenicol and two to trimethoprim. Sixty-three H influenzae strains were capsulated. Thirty-four of these were of Pittman type b, and antibiotic resistance, particularly to ampicillin, was more common in these than in other serotypes or non-typable strains. Some variation was seen in the resistance rate of both H influenzae and Str pneumoniae to tetracycline in strains from different centres, but too few were isolated to assess whether this represented a true geographical difference.

Penetration of antimicrobials into tissue culture cells and leucocytes.

Abstract: When exposed to HeLa cells in tissue culture for 72 hr., antimicrobials could be categorised into three groups characterised by cell associated concentrations much lower (ampicillin, cephalexin, cloxacillin, flucloxacillin, streptomycin and trimethoprim, all 14% or less), much higher (tetracycline and polymyxins) or approximating to those extracellularly (erythromycin, lincomycin, fusidic acid and gentamicin). For kanamycin, neomycin and sulphonamides, cell associated levels were between 24 and 47% and for penicillin G and cephaloridine were 66% of those extracellularly. With mouse peritoneal macrophages and human peripheral blood leucocytes cell associated levels for representative antibiotics were all lower after 3 hr. exposure than in the tissue culture cells. However, studies on the rate of release of cell associated antibiotic and of the effects of surface active agents indicated that the differences between cell types were due to loss of cell association during washing procedures to remove extracellular antibiotic. The effects of bactericidal antibiotics on survival of bacteria phagocytosed by mouse macrophages suggested that the cell association observed in tissue culture cells represented true intracellular penetration rather than mere binding to the cell surface. Within families of antibiotics, alterations to the molecule change cell penetration and the variations observed can not be explained merely in terms of simple diffusion, molecular size, dissociation constants, lipid solubility or protein binding.

Inactivation of Penicillin G during Experimental Infection with Bacteroides fragilis

Abstract: An animal model implanted with intraperitoneal plastic reservoirs was used for study of the penetration of penicillin G into sites infected with Bacteroides fragilis. Penicillin G was given to rabbits, and its concentration in uninfected reservoirs and in those infected with B. fragilis was determined. The mean percentage penetration ([concentration in capsule divided by peak concentration in serum] X 100) of penicillin into uninfected capsules was 19.9%, whereas that into heavily infected capsules was 1.5%. The percentage penetration of radiolabeled penicillin into infected capsules was 12.5%, whereas the proportion of bioactive drug in the same capsules was again very low (1%). These results show that there is a modest reduction in penetration of penicillin into infected sites and a striking inactivation of the drug by B. fragilis in this experimental model.

Listeria cerebritis. Relapse of infection in renal transplant patients.

Abstract: In 3 cases ofListeriacerebritis, two of the patients had relapse with cerebritis after antimicrobial therapy for acuteListeriasepticemia or meningitis. Each had received ten to 14 days of intravenous penicillin. Relapse occurred with fever and sudden focal cerebral dysfunction. Brain scans showed focal uptake; arteriograms and computerized tomography were normal. Cerebrospinal fluids were nondiagnostic; blood cultures yieldedListeriain two patients. Penicillin treatment for six weeks produced rapid clinical responses that were complete in one and minimal residual in two. Progress brain scans were normal. A relapse rate of 35% is reported in transplant patients withListeriameningitis and/or bacteremia who are treated for less than three weeks; to our knowledge, cerebritis in such patients has not been reported previously. High-dose penicillin or ampicillin therapy for four to six weeks is recommended forListeriainfections in this select group. (Arch Intern Med138:83-87, 1978)

Antimicrobial susceptibility patterns of Streptococcus pneumoniae.

Abstract: Fifty clinical isolates of Streptococcus pneumoniae received by the Streptococcus Laboratory of the Center for Disease Control from August 1976 through March 1977 and 50 pneumococcal strains retrieved from 13- to 16-year storage (originally isolated October 1961 through December 1964) were tested for susceptibility to 10 antimicrobial agents by disk-agar diffusion and agar dilution tests No appreciable differences in susceptibility patterns were apparent between the two groups, and, except for one isolate, all were highly susceptible to every drug tested except gentamicin This single isolate required higher drug concentrations to inhibit macroscopic growth and had corresponding decrements in zones of disk inhibition with penicillin, ampicillin, and cephalothin An additional 43 pneumococci recently received from various areas of the United States and Canada were screened by a disk agar diffusion method for penicillin resistance Four of these isolates had penicillin zone diameters <30 mm, and subsequent agar dilution test results showed that the penicillin minimum inhibitory concentrations were elevated with these organisms Antimicrobial susceptibility patterns of pneumococci to antimicrobials other than penicillin and its analogs have not changed substantially in over a decade However, due to the emergence of strains with decreased susceptibility to penicillin, the screening test for penicillin resistance in pneumococci, especially in isolates from spinal fluid and blood, could be clinically useful as an aid in selecting optimal therapy

Susceptibility of Campylobacter fetus to twenty-two antimicrobial agents.

Abstract: In vitro susceptibility of 11 recent clinical isolates of Campylobacter fetus to 22 antimicrobial agents was determined by an agar dilution technique. Unlike most obligate anaerobic gram-negative bacilli, C. fetus isolates tested were relatively resistant to penicillin and cephalosporins, but exquisitely susceptible to tetracyclines and aminoglycosides. All strains were also inhibited at concentrations achievable in serum by clindamycin, chloramphenicol, metronidazole, carbenicillin, ticarcillin, and with rare exceptions, ampicillin. They were variably susceptible to lincomycin and erythromycin and highly resistant to vancomycin.

Phenotypic and Epidemiologic Correlates of Auxotype in Neisseria gonorrhoeae

Abstract: Previous studies from Seattle, Wash., suggested that strains of Neisseria gonorrhoeae which require arginine, hypoxanthine, and uracil (Arg-Hyx-Ura- auxotype) are uniformly highly susceptible to penicillin G, are relatively resistant to complementdependent killing by heated, pooled human serum, and are associated with disseminated gonococcal infection. For further study of the epidemiology of these strains and for analysis of the susceptibility to penicillin, serum sensitivity, and the nutritional requirements of gonococcal isolates from other cities, a survey was made of urethral and cervical strains isolated in 1972-1974 from 50 randomly selected patients with uncomplicated gonorrhea from each of nine cities. Arg-Hyx-Ura- strains represented >50% of isolates from Seattle and Des Moines, Iowa, 22% of isolates from Denver, Colo., and Dayton, Ohio, and '12% of the isolates from Boston, Mass., Newark, N.J., Norfolk, Va., Miami, Fla., and Oakland, Calif. Arg-Hyx-Ura- strains were recovered from 42% of white and 9% of black patients (P < 0.001), and clinics with the highest incidences of these strains had the highest proportion of white patients among those with gonorrhea. Arg-Hyx-Ura- strains were all susceptible to '0.125 ,tg of penicillin G/ml and were more resistant than strains with other auxotypes to killing by heat-inactivated human serum plus complement (P < 0.01). Strains of Neisseria gonorrhoeae that require arginine, hypoxanthine, and uracil (Arg-Hyx-Uraauxotype) were associated with 89% of cases of

Susceptibility of 40 Lactobacilli to Six Antimicrobial Agents with Broad Gram-Positive Anaerobic Spectra

Abstract: The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of 40 lactobacillus strains were determined against six antibiotics with broad anaerobic spectra. Penicillin, ampicillin, clindamycin, and cephalothin were the most active inhibitory agents, with 95 to 100% of the strains inhibited at clinically achievable serum levels. However, despite the inhibitory efficacy of these four agents, only 5 to 22% of the isolates were killed at achievable concentrations. MBC:MIC ratios were high, ranging from 30:1 for cephalothin to 266:1 for ampicillin. Cefoxitin and metronidazole were generally ineffective against lactobacilli, with 87.5 to 100% of strains having unachievable MICs and/or MBCs. These findings may partially explain the clinical observations noting the inability to eradicate endocarditic lactobacillemias despite readily achievable MICs.

Short-term intramuscular therapy with procaine penicillin plus streptomycin for infective endocarditis due to viridans streptococci.

Abstract: Thirty-three patients with viridans streptococcal infective endocarditis were treated for two weeks with intramuscular procaine pencillin, 1.2 million units every 6 hours, plus streptomycin, 500 mg intramuscularly every 12 hours. Nine patients (27%) had infections with relatively penicillin-resistant microorganisms (MIC greater than 0.1 microgram/ml or MBC greater than or equal 3.12 microgram/ml). Follow-up ranged from 2 months to 3.5 years. There were no relapses; Mild vestibular toxicity developed in one patient. One patient died two months after completion of antimicrobial therapy from sudden onset of severe congestive heart failure; Seven patients required cardiac valve replacement after completion of antimicrobial therapy. None died. We believe that this therapeutic regimen is effective antimicrobial therapy for infective endocarditis caused by viridans streptococci, irrespective of in vitro microbiologic data.

Cephalosporin Antibiotics in Therapy of Experimental Streptococcus pneumoniae and Haemophilus influenzae Meningitis in Rabbits

Abstract: Six cephalosporin antibiotics (cefamandole, cefazolin, cephacetrile, cephalothin, cephaloridine, and cephradine) and two penicillins (ampicillin and penicillin G) were evaluated in vitro and in a rabbit model of experimental meningitis due to Haemophilus influenzae or Streptococcus pneumoniae. The percentage penetration ([concentration in cerebrospinal fluid/concentration in serum] X 100%) of these antibiotics varied from 0.7% for cephalothin to 17% for cephaloridine. The penetration varied inversely with binding to serum proteins. The bactericidal rate of all of the cephalosporin antibiotics was similar in vitro and in vivo to that of penicillin G. However, as demonstrated with cephalothin, concentrations considerably above the minimal bactericidal concentration (as determined in broth) were necessary to initiate the bactericidal effect. Cefamandole was found to be as effective as ampicillin in the therapy of H. influenzae meningitis in rabbits. Cephalosporin antibiotics are widely used as alter