Greater Bactericidal Activity Research Articles

Dexamethasone for children with bacterial meningitis. Should it be routine therapy?

Although most older infants and children develop normally after an episode of bacterial meningitis, some have subtle to moderate neurologic sequelae such as learning problems and speech delay, or suffer devastating neurologic injury. Although prevention of the disease is the optimal way to prevent neurologic damage due to bacterial meningitis, prompt and appropriate antimicrobial therapy and supportive care are the currently available means to limit or minimize neurologic sequelae. Newer antibiotics such as the third-generation cephalosporins have much greater in vitro activity againstHaemophilus influenzaetype b and are associated with greater bactericidal activity in cerebrospinal fluid than are ampicillin sodium or chloramphenicol sodium succinate. Therefore, it was hoped that the outcome of treatment with the newer agents would be superior to that following therapy with ampicillin or chloramphenicol. However, in all comparative trials to date, the outcome of children treated with the

Microbiological Evaluation of Copper : Silver Disinfection Units for Use in Swimming Pools

The bactericidal effects of electrolytically generated copper:silver ions on pathogenic bacteria of concern in swimming pools, hot tubs and cooling towers were evaluated in disinfection experiments. Copper:silver ion concentrations generated in well water were 400:40 µg/L, respectively. Pure cultures of Legionellapneumophila, Staphylococcusaureus, Pseudomonasaeruginosa, Escherichiacoli, and Streptococcusfaecalis, were individually tested in water containing copper:silver ions alone, copper:silver ions with free chlorine, and free chlorine alone. Greater numbers of organisms were killed after exposure to copper: silver ions with 0.2 mg/L free chlorine than in either the copper:silver ions or free chlorine alone. L. pneumophlla showed greater than a 5 log10 reduction in numbers after 7 minutes exposure to copper:silver ions with 0.2 mg/L free chlorine. In comparison, less than a 2 log10 decrease was obtained after exposure to free chlorine alone. E.coli numbers decreased over 4 log10 after 1 minute exposure to copper:silver ions with 0.2 mg/L free chlorine and less than a 3 log10 decrease after exposure to free chlorine alone. The majority of the other organisms tested showed the same effect. Electrolytically generated copper:silver ions with low levels of free chlorine appear to have greater bactericidal activities than either disinfectant alone.

Activity of teicoplanin compared with vancomycin alone, and combined with gentamicin, against penicillin tolerant viridans streptococci and enterococci causing endocarditis

Teicoplanin had greater inhibitory activity than vancomycin against most of 22 penicillin tolerant strains of streptococci, but both drugs failed to kill 99·9% of the inoculum when tested alone at concentrations less than 16mg1 −1. Bactericidal synergy between teicoplanin combined with gentamicin and vancomycin combined with gentamicin was always demonstrated in further tests with 16 penicillin tolerant strains. Teicoplanin had greater bactericidal activity than vancomycin against five of seven strains of viridans streptococci and five of nine strains of enterococci in MBC experiments, where each drug was combined with gentamicin. Killing curve experiments with five penicillin tolerant streptococci showed teicoplanin and vancomycin to have similar bactericidal activity within 24 h when tested at 5 mg1 −1 with 2 mg1 −1 gentamicin. However, at 0·5mg1 −1 only teicoplanin had a bactericidal synergic effect with gentamicin.

Human pharmacokinetics and antimicrobial activities of the temocillin epimers.

The pharmacokinetics of the epimers of temocillin were investigated in 4 healthy male subjects following intravenous administration of 1g of temocillin disodium (free acid) which contains a R : S epimer ratio of approximately 65 : 35. The R epimer had a 2-fold greater total plasma clearance, a 23% larger volume of distribution and a shorter beta half-life than the S epimer. Intermediate values were obtained for total temocillin (R + S) from high pressure liquid chromatography (HPLC) data. In each plasma sample, the unbound fraction of the R epimer was generally 2-fold higher than that of the S epimer, which is suggested as the reason for the differences in the pharmacokinetic properties of the epimers. The temocillin pharmacokinetic parameters obtained from the microbiological assay data reflect most closely those for the R epimer derived from HPLC data. The resolved R epimer exhibited twice the potency of the S epimer against the microbiological assay organism Pseudomonas aeruginosa NCTC 10701. However, in tests for antibacterial susceptibility, for instance minimum inhibitory concentration (MIC) determinations involving prolonged incubation, there was little difference in the inhibitory activities of the resolved R and S epimers compared with temocillin (R + S), presumably as a consequence of the epimerization of the individual epimers. In contrast, in rapid tests for bactericidal activity, which minimise the effect of epimerization, the R epimer exhibited greater bactericidal activity than the S epimer.

Age-dependent effects of aminobutyryl muramyl dipeptide on alveolar macrophage function in infant and adult Macaca monkeys.

We compared the antimicrobial function of alveolar macrophages (AM) from adult and 3- to 5-wk-old infant primates (Macaca nemestrina) and the effects of the immunomodulator, aminobutyryl muramyl dipeptide (abu-MDP) on this function. Phagocytosis of Staphylococcus aureus (SA) and group B streptococcus (GBS) by adult and infant AM was comparable. Adult and infant AM killed SA equally within 15 min of incubation; however, after 45 min, with phagocytosis of additional bacteria, adult AM had greater bactericidal activity (p less than 0.01). The bactericidal activity of infant and adult AM against GBS was comparable after 45 min of incubation; infant AM had slightly but significantly greater bactericidal activity with short incubation (15 min; p less than 0.025). The bactericidal activity of abu-MDP-treated infant AM against SA (p less than 0.01) and GBS (p less than 0.05) was greater than that of untreated infant AM and untreated or abu-MDP-treated adult AM. The abu-MDP did not significantly (p greater than 0.2) enhance the antimicrobial activity of adult AM. Catalase, but not superoxide dismutase or mannitol, significantly (p less than 0.005) increased survival of GBS in infant AM; this effect was comparable in abu-MDP-treated and in untreated AM. The abu-MDP-treated infant, but not the adult AM, released more acid phosphatase when triggered by opsonized zymosan than did untreated AM, but superoxide anion release by infant or adult AM was not affected by incubation with abu-MDP.(ABSTRACT TRUNCATED AT 250 WORDS)

Response to therapy in an experimental rabbit model of meningitis due to Listeria monocytogenes.

A uniformly fatal, reproducible model of experimental meningitis due to Listeria monocytogenes was developed in rabbits for study of the natural progression of the disease and was used to evaluate treatment regimens. Bacterial titers in cerebrospinal fluid and pleocytosis approximated those found in humans. Therapeutic studies in vivo revealed that rifampin was less rapidly bactericidal than ampicillin or penicillin, the agents usually recommended for treatment of meningitis; that penicillin plus rifampin was no more efficacious than penicillin alone; that ampicillin demonstrated greater bactericidal activity in vivo than did penicillin; and that addition of an aminoglycoside (gentamicin) to either penicillin or ampicillin significantly enhanced their bactericidal activity in vivo. Ampicillin plus gentamicin was the most effective combination in vivo and may represent the preferred mode of therapy for listeria meningitis.

In vitro and in vivo antibacterial activity of T-1220, a new semisynthetic penicillin.

T-1220, sodium 6-[d-(-)-alpha-(4-ethyl-2,3-dioxo-1-piperazinylcarbonyl-amino)- alpha-phenylacetamido] penicillanate, is a new semisynthetic penicillin derivative that possesses a broad spectrum of in vitro antibacterial activity against gram-positive and gram-negative bacteria. T-1220 is more effective than carbenicillin (CB-PC) against Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus species, and Serratia marcescens. Addition of human serum to culture media did not significantly alter the antibacterial activity of T-1220. Greater bactericidal activity toward various strains of gram-negative bacteria was demonstrated with T-1220 than with CB-PC. T-1220, like penicillin G, was hydrolyzed by penicillinase, but was sable to a type IV penicillinase produced by P. aeruginosa strains. In vivo antibacterial activities of T-1220, ampicillin (AB-PC), and CB-PC were compared, using systemic infections of mice with P. aeruginosa, K. pneumoniae, and Escherichia coli. The 50% effective doses (milligrams per kilogram) of T-1220 were consistently lower than those of AB-PC and CB-PC.

Chlorination, decarboxylation and bactericidal activity mediated by the MPO-H2O2-C1- system.

1. MPO, H2O2 and C1- form a complex that undergoes intramolecular rearrangement yielding the chlorinium ion. 2. The chlorinium ion can interact with MPO, bacteria and amino acids. 3. The reaction can occur at a wide range of pH, H2O2 concentration and C1- concentration. 4. The chlorinium ion can attack different protein molecules to cause structural changes. 5. Preincubation of MPO with bacteria results in greater bactericidal activity. 6. Diffusible bactericidal agents are also produced by the MPO-H2O2-C1- system.

Amoxycillin and Ampicillin

In vitro antibacterial activities of ampicillin and amoxycillin were compared against pigmented and non-pigmented strains of Serratia marcescens. Ampicillin appeared more effective than amoxycillin; three-fourths of all strains consistently exhibited an ampicillin minimum inhibitory concentration (MIC) of at least one tube less than that recorded for amoxycillin. Complete cross resistance was not observed as has previously been inferred. Further, greater bactericidal activity was demonstrated with ampicillin; minimum bactericidal concentrations (MBC) were either the same as or one tube greater than the MIC. MBC's for amoxycillin, however, were significantly higher; often four to five times greater than the MIC. Ampicillin exhibited greater bactericidal activity as inferred from differences observed in the biological lesions induced, as recorded through observations by scanning electron microscopy (SEM). Spheroplasts were the predominant morphological alteration induced by ampicillin. In contrast, only filament formation, which demonstrated a degree of reversibility, was induced by amoxycillin.

Function of Peroxidase in Resistance of Soybean to Bacterial Pustule1

Peroxidase activity of soybean [Glycine max (L.) Merr.] plants was determined to investigate its possible role in disease resistance. Activity of the enzyme was determined in mitochondrial and supernatant fractions obtained from roots of the near‐isogenic soybean cultivars ‘Clark’ and ‘Clark 63,’ susceptible and resistant, respectively, to bacterial pustule disease caused by Xanthomonas phaseoli var. sojensis. Peroxidase activity in both mitochondrial and supernatant fractions from roots of Clark 63 was greater than in those from Clark. Peroxidase activity was higher in the mitochondrial fraction than in the supernatant fraction from Clark 63.Peroxidase activity of the mitochondrial fraction from Clark 63 was threefold greater than that of Clark. Peroxidase was partially purified from mitochondria from roots of both cultivars. The peroxidase preparation from Clark 63 had greater bactericidal activity in the presence of hydrogen peroxide than that of Clark. There was a highly significant correlation between peroxidase activity per mg protein in the root preparations and percent survival of bacterial cells. A correlation coefficient of ∓0.7112 was obtained when ascorbic acid was present in the bactericidal assay system, and a coefficient of ∓0.6141 was obtained when ascorbic acid was omitted from the system.

Control of Surface Wound Infection: Skin Versus Synthetic Grafts

Auto-, iso-, or xenografts of skin and synthetics placed on surface wounds freshly contaminated with Pseudomonas aeruginosa stabilizes the wound bacterial population in rats over a 24-h period. When these wounds contained a bacterial contamination established for 24 h prior to grafting, only skin and the synthetic polyhydroxyethylmethacrylate were effective in lowering the initial bacterial concentration. Polyurethane foam and nylon velour were not effective in the established infection model. Skin placed on a contaminated wound for 2 h or longer appeared to equilibrate with the underlying muscle so that the bacterial count per milligram of skin was similar to that of the muscle. It was suggested that this preparation would be useful to obtain an estimate of surface contamination without biopsy of the infected muscle. Skin grafts in place for 2 h significantly lowered the bacterial count in a wound with an established infection. A second decrease occurred between 4 and 24 h after grafting. Histological studies of contaminated and exposed panniculus muscle showed that leukocytes tend to migrate from the muscle surface to its base. Skin grafts and polyhydroxyethylmethacrylate appear to reverse the white cell migration so that the cells move toward the surface of the muscle with preservation of normal staining characteristics in the muscle. It is suggested that this alteration in cell movement after graft application might modify the white cell function and result in a greater bactericidal activity. Apparently, grafts lower bacterial levels in an established infection by modifying the host response to the surface contamination.

Immunity to Experimental Infection with Corynebacterium ovis in the Mouse Peritoneal Cavity

Immunization of mice by intraperitoneal injections of an attenuated strain of Corynebacterium ovis led to the acquisition of a strong degree of resistance to infection with the virulent strain, measured as a greater bactericidal activity within the peritoneal cavity and a significant decrease in the development of internal lesions. The acquired immunity became manifest on about the fourth day after initial infection and was non-specific. It appeared to be associated with the resident mononuclear phagocytes of the immunized peritoneal cavity which were increased in numbers, larger in size and had altered staining properties.

In vitro studies on the choice of drugs for intermittent chemotherapy of tuberculosis

Summary An attempt was made to study the effect of exposing cultures of Myco. tuberculosis for short periods to drugs used in the treatment of tuberculosis. Six drugs were used, the concentration of each being approximately ten times that necessary to inhibit growth. The cultures were exposed to these drugs for periods varying from two to 168 hours. Estimates of the number of viable organisms in the cultures were made before their exposure and at intervals after removal of the drug by washing with drug-free medium on a membrane filter. The effect of exposure was estimated by noting the delay before the organisms again began to grow. Streptomycin was considered most suitable for intermittent chemotherapy since it had the greatest bactericidal activity and the delay before growth began after exposure to the drug for six-96 hours and its subsequent removal, was eight-16 days; growth of organisms between doses would thus not be expected. Isoniazid and ethionamide appeared slightly less suitable as they only began to be bactericidal if the exposure period was at least one day and there was no delay before growth after exposure periods of 12 hours or less. However, after exposure periods of 24 hours or more, the delay before growth was three-17 days. With cycloserine, the delay before growth was only about one day after exposure for 24 hours but during exposure for 96 hours, this drug was more bactericidal than either isoniazid or ethionamide, and the delay before growth was then four-eight days. Thiacetazone and thiocarlide (4-4′ diisoamyloxythiocarbanilide) did not appear suitable for intermittent use since they were not bactericidal and growth started immediately after exposure.

Studies of aerogenic and anaerogenic variants of Salmonella schottmuelleri. II. Resistance to antibiotics and sulfadiazine.

1. A study of relative resistances of six colonial types representing aerogenic and anaerogenic mucoid, smooth, and rough forms ofS. schottmuelleri to various antibiotics and sulfadiazine is presented. 2. Marked differences in susceptibility between the various colonial types, when tested both by the paper-disc and tube-dilution — subtransfer methods, were noted. The aerogenic smooth and rough colony types and the anaerogenic smooth form proved to be most resistant, while the mucoid forms and the anaerogenic rough form were most susceptible. 3. Penicillin and chloromycetin were the most effective drugs when tested by the paper-disc method, while penicillin showed greatest bactericidal activity and chloromycetin least activity of the antibiotics when tested by the tube method. Whereas terramycin was more effective than aureomycin when evaluated by the paper-disc method, both were equally efficient when tested by the tube-dilution — subtransfer method. Streptomycin followed these two antibiotics in efficiency when tested by both methods. Sulfadiazine was the least active drug used in these studies. 4. From our study no exact comparisons of results can yet be made between the two methods of testing.

Sulfamylon in the treatment of external otitis.

Sulfamylon^®is rapidly gaining popularity in the local treatment of ear, nose and throat infections as a very effective bactericidal and bacteriostatic agent. It is a sulfanilamide derivative with a chemical formula of SO₂NH₂.C₆H₄.CH₂NH₂.HCL; its chemical name is para(aminomethyl)-benzene sulfonamide hydrochloride. It is a white crystalline material, soluble in water, and weakly acid in reaction. Although it is a sulfonamide derivative, research chemists have altered the sulfonamide structural formula to produce sulfamylon^®; unlike the original drug, it is nontoxic and is active in the presence of paraaminobenzoic acid, blood, tissue juices, and pus. The in vitro experimental work was done to a large extent by Brewer,¹who compared concentrations of sulfamylon^®and sodium sulfadiazine and sulfathiazole. In this work he found that sulfamylon^®had a much greater bactericidal activity than either of the