bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of ampicillin resistance plasmids from Haemophilus ducreyi
Authors: Totten P A , Handsfield H H , Peters D , Holmes K K , Falkow S
Published: June 2012

Seven strains of Haemophilus ducreyi from diverse geographic origins were analyzed for their plasmid content. All strains were multiply resistant, but only resistance to ampicillin was transferred to Escherichia coli by transformation. The H. ducreyi plasmids encoding for ampicillin resistance were 7.4, 5.7, and 3.6 megadaltons and encoded for part or all of TnA, and ampicillin transposon. The relatedness of these plasmids was examined by restriction endonuclease digestion and DNA-DNA homology with isolated DNA fragments from TnA.
Comparative in vitro study of temocillin (BRL 17421), a new penicillin
Authors: Bolivar R , Weaver S S , Bodey G P
Published: June 2012

The activity of temocillin (BRL 17421), a new penicillin, was tested in vitro against 653 isolates of gram-negative bacilli and gram-positive cocci. The drug was compared with other beta-lactam antibiotics and tobramycin. It inhibited the majority of gram-negative bacilli tested except for Pseudomonas aeruginosa and Acinetobacter calcoaceticus, which were highly resistant. It was active against more than 50% of the multiresistant strains tested. Temocillin was more active than mezlocillin against most gram-negative bacilli and more active than moxalactam, ceftriaxone, and ceftazidime against Enterobacter spp. In general, it was slightly less active than the other drugs tested and had no activity against the gram-positive cocci. There was no significant change in drug activity when pH and medium were varied, and the effect of serum binding was minimal. There was no significant inoculum effect when the size of the inoculum was increased from 10(4) to 10(6) organisms per ml.
Mutational Enzymatic Resistance of
Enterobacter
Species to Beta-Lactam Antibiotics
Authors: Lampe Mary F. , Allan Barbara J. , Minshew Barbara H. , Sherris John C.
Published: June 2012

Mutants with enhanced β-lactam resistance were selected from strains of
Enterobacter cloacae
and
E. aerogenes
by using three antibiotics. High-level β-lactamase-producing mutants had similar degrees of increased resistance, enzyme substrate profiles, and isoelectric (pI) values irrespective of the selective agent. Reverse mutants from a resistant
E. cloacae
mutant regained the susceptibility pattern originally exhibited by the wild type, or were of enhanced susceptibility, and no longer expressed increased β-lactamase production. β-Lactamases of the mutants were similar in pI values to the wild-type enzyme. The increased resistance of the mutants therefore appeared to be accounted for by increased β-lactamase production.
Antimicrobial Susceptibility of
Bordetella pertussis
Strains Isolated from 1960 to 1981
Authors: Bannatyne Robert M. , Cheung Rose
Published: June 2012

The susceptibilities to erythromycin, rifampin, polymyxin B, ampicillin, tetracycline, gentamicin, fusidic acid, trimethoprim, and spectinomycin of 100 strains of
Bordetella pertussis
isolated between 1960 and 1981 were compared. No change in susceptibility to any of these drugs was noted.
Gentamicin Does Not Chelate Calcium
Authors: Kohlhepp Sue J. , Plant Sandford B. , McCarron David A. , Gilbert David N.
Published: June 2012

The influence of increasing gentamicin concentrations on ionized calcium concentration was determined in pH-controlled, phosphate-buffered saline and normal human serum with an ion-specific calcium electrode. No evidence of calcium chelation was found.
In vitro activity of MK-0366 against clinical urinary pathogens including gentamicin-resistant Pseudomonas aeruginosa
Authors: Downs J , Andriole V T , Ryan J L
Published: June 2012

MK-0366, a new derivative of nalidixic acid, was tested against 250 urinary pathogens including Escherichia coli, Serratia marcescens, and Pseudomonas aeruginosa. This new agent was more active than any of the other antibiotics tested, which included carbenicillin, ampicillin, cephalexin, tetracycline, trimethoprim, trimethoprim-sulfamethoxazole, and nalidixic acid. Gentamicin-resistant P. aeruginosa were highly sensitive to MK-0366, with a 90% minimal inhibitory concentration of 0.8 microgram/ml. Serratia strains were the most resistant organisms, with a 90% minimal inhibitory concentration of 3.1 micrograms/ml. These results suggest that clinical trials should be designed to investigate the clinical usefulness of this new drug in urinary infections.
Comparative In Vitro Activities of
N
-Formimidoyl Thienamycin and Moxalactam Against Nonfermentative Aerobic Gram-Negative Rods
Authors: O'Donnell Edward D. , Freimer Earl H. , Gilardi Gerald L. , Raeder Roberta
Published: June 2012

N
-Formimidoyl thienamycin was the most active drug against strains of
Pseudomonas aeruginosa
with a 90% minimum inhibitory concentration of 1.25 μg/ml. With the exception of
P. maltophilia
, thienamycin was as active or more active than moxalactam against other species of pseudomonads and against other genera of nonfermenters.
Conjugative R plasmids in Streptococcus faecium (group D)
Authors: Le Bouguenec C , Horodniceanu T
Published: June 2012

Ten isolates of Streptococcus faecium were found to be resistant to penicillin, tetracycline, macrolides and related drugs, streptomycin, and kanamycin, and four strains were resistant to chloramphenicol. Six of these 10 strains transferred all their resistance markers (except penicillin) by conjugation at a low frequency (10(-7) to 10(-9)). Several plasmids of different molecular weights were found in each of the wild-type strains. In 5 of 11 transconjugant strains, R plasmids were detected which had molecular weights identical to those of the plasmids found in the corresponding donor strain. Each of the six other transconjugants harbored one plasmid with a size different from those found in the corresponding donor strain, suggesting the occurrence of molecular events during or after conjugative transfer. None of the five tetracycline-resistant transconjugants contained detectable satellite DNA, HindIII restriction enzyme fingerprints of S. faecium resistance plasmids were different from the HindIII patterns of macrolide, aminoglycoside, and tetracycline resistance plasmids from other strains of streptococci.
Structural and phenotypic varieties of gentamicin resistance plasmids in hospital strains of Staphylococcus aureus and coagulase-negative staphylococci
Authors: Jaffe H W , Sweeney H M , Weinstein R A , Kabins S A , Nathan C , Cohen S
Published: June 2012

We previously described a neonatal nursery epidemic of infections caused by a single strain of Staphylococcus aureus bearing a gentamicin resistance plasmid (Vogel et al., Antimicrob. Agents Chemother. 13:466-472, 1978). The same plasmid was present in two isolates of Staphylococcus epidermidis from the patients in this nursery and was transferable interspecifically from either S. aureus or S. epidermidis. During the ensuing 3 years, in the absence of further epidemics, we collected 162 gentamicin-resistant strains of S. aureus and coagulase-negative staphylococci from patients distributed throughout our hospital. Gentamicin resistance plasmids obtained from 41 representative S. aureus and coagulase-negative staphylococcal strains differed as determined by phenotypic and molecular analyses from the plasmid in the neonatal nursery epidemic. Nevertheless, these plasmids were structurally related to each other and to the plasmid of the original epidemic. Our results suggest an evolutionary relationship among these plasmids and support the hypothesis of a genetic reservoir of gentamicin resistance in coagulase-negative staphylococci transferable to S. aureus.
Anti-influenza A virus activity of amantadine hydrochloride and rimantadine hydrochloride in ferret tracheal ciliated epithelium
Authors: Burlington D B , Meiklejohn G , Mostow S R
Published: June 2012

The activities and toxicities of amantadine hydrochloride and rimantadine hydrochloride against influenza A/Alaska/6/77 (H3N2) and A/Bangkok/1/79 (H3N2) viruses were compared in organ cultures and ferret tracheal ciliated epithelium. Pretreatment of cultures with concentrations (0.5 and 1 micrograms/ml) comparable to those found in human serum after oral administration of amantadine revealed that rimantadine produced significantly longer protection than amantadine against virus-induced cytopathic effects. Correspondingly, rimantadine produced a comparable protective effect at four- to eight-fold-lower concentrations than amantadine. Both drugs produced increasing and similar effects at higher concentrations, which were comparable to those reported in nasal washings after aerosol administration of amantadine. At the concentrations tested, amantadine was nontoxic. However, at concentrations of 16 and 32 micrograms/ml, rimantadine was toxic to the ciliated epithelium after 10 to 21 days of continuous exposure. When the drugs were added 24 h or more after infection, protection against cytopathic effects decreased markedly. Both drugs moderately suppressed virus production at concentrations of 0.5 to 16 micrograms/ml. However, no dose response or difference between the drugs was observed. Because of comparable antiviral activity at lower concentrations and greater activity at similar concentrations, rimantadine may be more useful than amantadine for oral prophylaxis and therapy of influenza.
Rifampin blood and tissue levels in patients undergoing cardiac valve surgery
Authors: Archer G L , Armstrong B C , Kline B J
Published: June 2012

Single 600-mg capsules of rifampin were given orally to 26 patients as prophylaxis during cardiac valve replacement. Antibiotic concentrations were measured in blood (serum or plasma) and tissue (excised cardiac valve). The serum or plasma levels of rifampin in 18 patients who ingested this drug 2 h before they received preoperative opiates and anticholinergics intramuscularly were not significantly different from the levels in four normal volunteers who received the drug. These levels were 15.9 +/- 6.5 micrograms/ml (mean +/- standard deviation) 2 h after drug administration, 7.1 +/- 4.3 micrograms/ml 8 h after drug administration and 2 h after a mean of 1.4 h on cardiopulmonary bypass, and 1.6 +/- 1.6 micrograms/ml 24 h after drug ingestion. The valve tissue level was 3.8 +/- 2.7 micrograms/g (mean +/- standard deviation; n = 10). This value was 65% of the simultaneous serum and plasma levels and 31% of the peak serum and plasma levels. Eight patients who were given rifampin at the same time that they received other preoperative medications had significantly lower blood levels than the 18 patients who received rifampin 2 h earlier (P less than 0.001). No rifampin was detected in valves from seven of these patients. Decreased rifampin absorption due to simultaneous administration with opiates and anticholinergics was the probable reason for the low plasma and serum levels observed. These data suggest that, if properly dosed, rifampin administered orally gives high blood and valve tissue levels, which are affected minimally by cardiopulmonary bypass in patients undergoing cardiac valve surgery.
Effects of probenecid on the pharmacokinetics and elimination of acyclovir in humans
Authors: Laskin O L , de Miranda P , King D H , Page D A , Longstreth J A , Rocco L , Lietman P S
Published: June 2012

The effects of probenecid on the pharmacokinetics and renal clearance of acyclovir were studied in humans. Acyclovir (5 mg/kg) was given as a 1-h infusion to three volunteers with normal renal function both before and after oral administration of probenecid (1 g). The kinetics were well described by a two-compartment open model with zero-order infusion. The mean acyclovir concentrations at all time points after 1.0 h from the end of acyclovir infusion following probenecid administration were statistically higher than the corresponding mean acyclovir concentrations following the acyclovir infusion without probenecid administration. In the absence of probenecid, the renal clearance (248 +/- 80 ml/min per 1.73 m2) accounted for 83% of the total clearance (300 +/- 69 ml/min per 1.73 m2) and was almost threefold greater than the estimated creatinine clearance (90 +/- 48 ml/min per 1.73 m2). After probenecid administration, there was a 32% decline in renal clearance (248 to 168 ml/min per 1.73 m2; P less than or equal to 0.05), a 40% increase in the area under the curve (91.3 to 127.6 nmol.h/ml; P less than 0.05), and an 18% increase in the terminal plasma half-life (2.3 to 2.7 h; P less than 0.01). Although statistically significant, these effects due to the influence of probenecid probably have only limited clinical importance. In this study we confirmed that acyclovir is eliminated predominantly by renal clearance, both by glomerular filtration and tubular secretion; our results suggested that at least part of the tubular secretion is inhibited by probenecid.
Tetracycline resistance of Corynebacterium diphtheriae isolated from diphtheria patients in Jakarta, Indonesia
Authors: Rockhill R C , Sumarmo  , Hadiputranto H , Siregar S P , Muslihun B
Published: June 2012

Of 133 Corynebacterium diphtheriae isolates from diphtheria patients in Jakarta, Indonesia, 86% were resistant to greater than or equal to 32 micrograms of tetracycline per ml. All isolates were sensitive to ampicillin, cephalothin, chloramphenicol, clindamycin, penicillin, erythromycin, and kanamycin. The general resistance of C. diphtheriae to tetracycline in this part of Indonesia appears to be unique compared with resistance reported in studies done in other parts of the world.
Molecular epidemiology of beta-lactamase-specifying plasmids of Haemophilus ducreyi
Authors: Brunton J , Meier M , Ehrman N , Maclean I , Slaney L , Albritton W L
Published: June 2012

We have studied the genetic basis of beta-lactamase production in eight strains of Haemophilus ducreyi isolated in diverse areas of the world. Beta-lactamase production in all strains was mediated by plasmids having a molecular mass of either 5.7 or 7.0 megadaltons. Plasmids of 5.7 megadaltons were shown to carry the entire sequence of pFA7, the beta-lactamase specifying plasmid found in isolates of Neisseria gonorrhoeae epidemiologically linked to West Africa. Plasmids of 7.0 megadaltons were shown to carry the entire sequence of pFA3, the beta-lactamase specifying plasmid found in Far Eastern isolates of N. gonorrhoeae. Both groups of H. ducreyi plasmids were shown to carry physically complete and functional TnA sequences. Thus we have identified two types of H. ducreyi beta-lactamase plasmid which are identical to the two types of N. gonorrhoeae beta-lactamase plasmid, except that they carry complete TnA sequences.
Effects of low concentrations of antibiotics on Escherichia coli adhesion
Authors: Vosbeck K , Mett H , Huber U , Bohn J , Petignat M
Published: June 2012

We have previously shown that subinhibitory concentrations of antibiotics may influence the adhesion of Escherichia coli SS142 to human epithelioid tissue culture cells. This report shows that these effects are not limited to E. coli SS142 or to our tissue culture system. Most of the 10 E. coli strains studied showed decreased adhesion to Intestine 407 tissue culture cells after growth in 25% of the minimum inhibitory concentration of streptomycin, tetracycline, trimethoprimsulfametrole, chloramphenicol, and clindamycin. Nalidixic acid at 25% of the minimum inhibitory concentration caused an increase of adhesion. The hemagglutinating activity of the five hemagglutinating strains and the adhesiveness of E. coli SS142 to human buccal cells were similarly affected by low concentrations of the above-mentioned antibiotics. We conclude that E. coli adhesion to human epithelioid tissue culture cells is a valid model of bacterial adhesion because of its high accuracy and reproducibility.
In vitro susceptibility of Gardnerella vaginalis and Bacteroides organisms, associated with nonspecific vaginitis, to sulfonamide preparations
Authors: Jones B M , Kinghorn G R , Geary I
Published: June 2012

Recent reports suggest that anaerobic Bacteroides organisms are frequently found with Gardnerella vaginalis in nonspecific vaginitis. Specimens taken from 96 women with vaginal discharge were tested simultaneously for these organisms. G. vaginalis was found in 73% of the specimens, Bacteroides was found in 53%, and both organisms were found in 47%. Sulfonamides have been widely used in the successful treatment of vaginitis. Paradoxically, G. vaginalis is reported to be resistant, and it has been suggested that it could be the vehicle of the drugs which effects the cure. Little is known of the susceptibility of vaginal anaerobes to the sulfonamides. G. vaginalis and Bacteroides isolates were therefore tested in vitro against the individual excipients of sulfonamide tablets, and minimal inhibitory concentration tests were also performed against the three active drugs. The excipients had no effect on G. vaginalis, but Bacteroides strains were susceptible to the urea component. All strains of both organisms were susceptible to at least two of the three sulfonamides at high concentrations.
Mechanism of action of the copper(I) complex of 2,9-dimethyl-1,10-phenanthroline on Mycoplasma gallisepticum
Authors: Smit H , van der Goot H , Nauta W T , Timmerman H , de Bolster M W , Stouthamer A H , Vis R D
Published: June 2012

Evidence was found that the inhibitory action of Cu(DMP)2NO3, the copper(I) complex of 2,9-dimethyl-1,10-phenanthroline (DMP), on Mycoplasma gallisepticum is a consequence of the ultimate toxicity of copper, and not that of the ligand, DMP. From uptake studies with radiolabeled 67Cu and [14C]DMP, we concluded that significantly more copper than DMP is bound to the mycoplasmal cell. It appeared that dissociation of Cu(DMP)2+ occurred shortly after interaction with the cell membrane. Copper was transported across the cytoplasmic membrane. A strong dependence of copper uptake on the incubation medium was observed in the absence of DMP. The main function of the ligand DMP appeared to be as a vehicle for the transport of copper from nontoxic copper-medium complexes to membrane-buried cellular ligands.
Long-term venous access in rhesus monkeys
Authors: Hoeprich P D , Wolfe B M , Jerome C , Olson D A , Huston A C
Published: June 2012

Long-term, intermittent, intravenous infusion of substances, such as amphotericin B, with a high potential for causing peripheral vein thrombophlebitis was feasible by means of a subcutaneously implanted silastic reservoir catheter device, which gave access to the central venous compartment. The implanted reservoirs withstood at least 100 percutaneous entries with a 27-gauge needle; injections were carried out by using an infusion pump. With precautions taken to prevent infection, clotting, or the formation of precipitates in the catheter, the device permitted easy intravenous injection and was well tolerated.
Susceptibility pattern of Campylobacter jejuni from human and animal origins to different antimicrobial agents
Authors: Vanhoof R , Goossens H , Coignau H , Stas G , Butzler J P
Published: June 2012

The in vitro antimicrobial activities of different antimicrobial agents on Campylobacter jejuni from human and animal origins were compared by using a Dynatech MIC 2000 system. In general, the minimal inhibitory concentration distributions for the human strains were very comparable with those of the animal strains. The animal strains had a bimodal distribution for ampicillin, clindamycin, and tetracycline.
Ceftriaxone: in vitro studies and clinical evaluation
Authors: Gnann J W , Goetter W E , Elliott A M , Cobbs C G
Published: June 2012

The in vitro activity of ceftriaxone against 437 clinical isolates of gram-negative bacilli was determined. Ceftriaxone was found to have high in vitro activity against Enterobacteriaceae, with the exception of Enterobacter cloacae. Ceftriaxone was only minimally active against Pseudomonas aeruginosa and Acinetobacter calcoaceticus. We evaluated the clinical efficacy and toxicity of ceftriaxone in 55 adult patients. Bacterial infection was confirmed by the isolation of etiological bacteria in 30 patients. Infectious disorders treated included 10 pneumonias, 13 urinary tract infections, and 7 soft tissue or bone infections. Pathogens identified were 25 isolates of gram-negative bacilli, 5 isolates of Staphylococcus aureus, 5 isolates of pneumococci, and 4 isolates of other streptococci. The overall efficacy of ceftriaxone was excellent. The clinical cure rate was 93%, and the bacteriological cure rate was 93%. A total of 30 adverse reactions were noted in 22 of 55 patients receiving ceftriaxone, but only one necessitated discontinuation of treatment. Adverse effects frequently noted were elevated hepatic enzymes (16%), thrombocytosis (16%), and eosinophilia (8%). Ceftriaxone is an effective and well-tolerated antimicrobial agent that appears promising for the treatment of serious gram-negative bacillary infections.
In vitro synergistic activity of ethambutol, isoniazid, kanamycin, rifampin, and streptomycin against Mycobacterium avium-intracellulare complex
Authors: Zimmer B L , DeYoung D R , Roberts G D
Published: June 2012

Strains of Mycobacterium avium-intracellulare complex often exhibit in vitro resistance to common antimycobacterial agents. Combinations of etambutol, isoniazid, kanamycin, rifampin, and streptomycin were tested to determine if synergism occurred. Ninety-six percent of the strains were susceptible to a combination of ethambutol and rifampin at concentrations attainable clinically. Other combinations of antimycobacterial agents inhibited 4 to 82% of the isolates tested.
In vitro activity of temocillin (BRL 17421), a novel beta-lactamase-stable penicillin
Authors: Verbist L
Published: June 2012

The new in vitro activity of temocillin (BRL 17421), a new beta-lactamase-stable penicillin, was compared with those of other beta-lactam antibiotics for over 500 clinical bacterial isolates. Temocillin inhibited 94% of the Enterobacteriaceae organisms at concentrations of 0.5 to 8 microgram/ml, regardless of organisms resistance to ampicillin, ticarcillin, cefazolin, or combinations thereof. Most pseudomonas aeruginosa isolates and all staphylococci and streptococci tested were resistant to temocillin.
Comparative in vitro activities of azlocillin-cefotaxime and azlocillin-tobramycin combinations against blood and multi-drug resistant bacterial isolates
Authors: Fass R J
Published: June 2012

The in vitro activities of azlocillin and cefotaxime in combination and of azlocillin and tobramycin in combination against 100 blood isolates and 50 multidrug-resistant isolates were compared. With both combinations, antibacterial spectrums were complementary. Although synergy against individual strains was infrequently observed (except for azlocillin-cefotaxime against Streptococcus faecalis and azlocillin-tobramycin against Pseudomonas aeruginosa), 97% of blood isolates and 76% of multidrug-resistant isolates were susceptible to azlocillin-cefotaxime, and 94% of blood isolates and 36% of multidrug-resistant isolates were susceptible to azlocyclin-tobramycin.
A new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxyl]methyl]guanine, highly active in vitro against herpes simplex virus types 1 and 2
Authors: Smith K O , Galloway K S , Kennell W L , Ogilvie K K , Radatus B K
Published: June 2012

A novel nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]-guanine (BIOLF-62), was found to have potent antiviral activity against herpes simplex virus types 1 and 2 at concentrations well below cytotoxic levels. For example, the Patton strain of herpes simplex virus type 1 was susceptible at concentrations 140- to 2,900-fold below that which inhibited cell division by 50%, depending upon the cell line used for assay. Different herpesvirus strains varied considerably in their susceptibility to the drug, as did results obtained with the same virus strain in different cell lines. BIOLF-62 compared favorably with 5-iodo-2'-deoxyuridine and acyclovir with respect to ratios of viral to cell inhibitory drug concentrations. Patterns of drug resistance to herpesvirus mutants suggested that the primary mode of action of BIOLF-62 is different from that of known antiviral compounds. Human adenovirus type 2, varicella-zoster virus, and Epstein-Barr virus were inhibited by this drug but at concentrations within the cell inhibitory range. Vaccinia virus and human cytomegalovirus were not inhibited at high drug concentrations.
Extracellular proteases increase tolerance of Bacillus subtilis to nafcillin
Authors: Jolliffe L K , Doyle R J , Streips U N
Published: June 2012

Mutants of Bacillus subtilis capable of secreting high amounts of protease were highly tolerant to the lethal and lytic effects of nafcillin. Protease-deficient mutants were more susceptible. However, when subtilisin was added to exogenously to a protease-deficient strain, the organism assumed the characteristics of nafcillin tolerance. Similarly, when phenylmethylsulfonyl fluoride, a serine protease inhibitor, was added to the tolerant strains, they became susceptible to nafcillin-induced lysis. The effects of nafcillin on B. subtilis were studied with both viability determinations and assay of cellular lysis. The minimum inhibitory concentrations of nafcillin tended to be higher for the protease hyperproducing strains, but these values could be reduced by the protease inhibitor. No loss of antibiotic activity was observed when nafcillin was incubated with either subtilisin or trypsin. Furthermore, protease and autolysin from B. subtilis were not modified by nafcillin. The results showed that extracellular proteases could render B. subtilis relatively tolerant to the killing and lytic effects of a cell wall antibiotic. The proteases were probably acting on the autolysins of the organism, thereby increasing tolerance to nafcillin.
Penetration of moxalactam and cefazolin into atrial appendage after simultaneous intramuscular or intravenous administration
Authors: Polk R E , Smith J E , Ducey K , Lower R R
Published: June 2012

This study compared the penetration of moxalactam and cefazolin into the human atrial appendage after simultaneous administration of both drugs by two routes. Nineteen adult patients scheduled for coronary vein bypass surgery randomly received 10 mg of moxalactam and cefazolin per kg by either the intramuscular or intravenous (bolus) route on administration of anesthesia. Concentrations of cefazolin in serum were significantly greater than concentrations of moxalactam at all times for both routes of administration. There were no significant differences, however, in the concentration of these drugs in atrial appendages, although concentrations of both agents administered intravenously were significantly greater than of drugs administered intramuscularly. (19.3 +/- 10.3 and 21.0 +/- 11.0 micrograms intravenously versus 8.3 +/- 3.6 and 10.1 +/- 3.2 micrograms/g intramuscularly for moxalactam and cefazolin, respectively).
Conjugative transfer of R-plasmids from Streptococcus faecalis to Staphylococcus aureus
Authors: Schaberg D R , Clewell D B , Glatzer L
Published: June 2012

R-plasmids originally isolated from Streptococcus pyogenes(pAC1,pAM15346), Streptococcus agalactiae(pIP501), and Streptococcus faecalis(pAM beta 1) were shown to be self-transferable on filter membranes from S. faecalis JH2-2 to Staphylococcus aureus recipients. The nonconjugative plasmid pAM alpha 1 was mobilized into S. aureus by pAM beta 1. Once in S. aureus, conjugative R-plasmids could be transferred to a second S. aureus recipient or back into S. faecalis. Determinants for chloramphenicol, clindamycin, erythromycin, and tetracycline resistances present on these streptococcal plasmids were expressed in S. aureus. Agarose gel electrophoresis, dye-buoyant centrifugation, and restriction endonuclease digestion showed that the plasmids were maintained intact as self-replicating elements in S. aureus recipients.
Antimicrobial susceptibility of Streptococcus pneumoniae: serotype distribution of penicillin-resistant strains in Spain
Authors: Casal J
Published: June 2012

This study examined the resistance to penicillin, tetracycline, erythromycin, and chloramphenicol of 318 pneumococcal strains isolated in Spanish hospitals from blood or cerebrospinal fluid of patients during 1979 to 1981. The serotypes of these strains were determined to discover whether a correlation between serotype and patterns of antibiotic resistance could be found. Seven and nine patterns of resistance were found in strains isolated from blood and cerebrospinal fluid, respectively; tetracycline was the most frequent pattern, followed by tetracycline associated with chloramphenicol. A random distribution of serotypes which was similar to the general distribution of serotypes was found for resistance to tetracycline and chloramphenicol, but penicillin-resistant strains were confined to seven serotypes. Thirty-six strains of penicillin-resistant pneumococci isolated from sources other than blood or cerebrospinal fluid were also serotyped. They represented the same serotypes, suggesting that serotype distribution among penicillin-resistant strains could be a manifestation of local epidemiological factors.
Bactericidal activity of antibiotics against Legionella micdadei (Pittsburgh pneumonia agent)
Authors: Dowling J N , Weyant R S , Pasculle A W
Published: June 2012

The bactericidal activity of five antibiotics for Legionella micdadei was determined by the construction of time-kill curves. Erythromycin, rifampin, penicillin G, cephalothin, and gentamicin were bactericidal for L. micdadei at readily achievable concentrations. The minimal bactericidal concentrations, defined as those producing 99.9% killing within 24 h, were: erythromycin, 4.6; rifampin, 0.13; penicillin G, 0.25; cephalothin, 2.5; and gentamicin, 0.25 micrograms/ml. The ratios of the minimal bactericidal to minimal inhibitory concentrations for these antibiotics ranged from 1 to 8. Thus, the poor in vivo activity of beta-lactam and aminoglycoside antibiotics against L. micdadei cannot be ascribed to a lack of killing by these agents.
A comparison of the antibacterial activities of N-formimidoyl thienamycin (MK0787) with those of other recently developed beta-lactam derivatives
Authors: Cullmann W , Opferkuch W , Stieglitz M , Werkmeister U
Published: June 2012

The antibacterial activity of N-formimidoyl thienamycin (MK0787) was evaluated in 335 clinical isolates of ampicillin-resistant Enterobacteriaceae, 50 Pseudomonas aeruginosa strains, 28 Acinetobacter spp., 50 Streptococcus faecalis strains, and 7 oxacillin-resistant Staphylococcus aureus strains and was compared with the recently developed beta-lactam antibiotics mezlocillin, cefuroxime, cefazedone, cefoperazone, cefotaxime, and moxalactam. Among the gram-negative bacteria, N-formimidoyl thienamycin was less active than cefotaxime against Klebsiella, Serratia, and Proteus spp. but had comparable activity against Escherichia coli and Enterobacter strains. Activity of the thienamycin derivative was somewhat lower than that of moxalactam against most of the strains and superior to that of mezlocillin, cefuroxime, and cefoperazone. Moreover, N-formimidoyl thienamycin was the most active drug against P. aeruginosa and Acinetobacter spp. and had activity comparable to that of ampicillin against Streptococcus faecalis. N-Formimidoyl thienamycin was bactericidal at concentrations less than twice the minimal inhibitory concentration (MIC) in all gram-negative isolates tested. Oxacillin-resistant staphylococci (MIC of oxacillin, greater than 4 micrograms/ml) were inhibited at low concentrations of the thienamycin derivative (90% MIC, 0.25 micrograms/ml); however, N-formimidoyl thienamycin was not bactericidal at the 90% MIC. The antibacterial activity of N-formimidoyl thienamycin against all of the gram-negative bacilli was observed to be independent of beta-lactamase production.
Elimination kinetics of ceftizoxime in humans with and without renal insufficiency
Authors: Ohkawa M , Okasho A , Sugata T , Kuroda K
Published: June 2012

The pharmacokinetics of a single 500-mg intramuscular dose of ceftizoxime were studied in 11 healthy adult volunteers and in 22 patients with various degrees of renal dysfunction. The mean serum half-life of ceftizoxime was 1.44 h in normal subjects and 30.2 h in hemodialysis patients. A significant correlation (P less than 0.001) between the elimination rate constant of ceftizoxime and creatinine clearance was demonstrated. The mean urinary recovery in normal subjects was 75.6% within 6 h of dosage; recovery decreased progressively with reduced renal function.
Comparative in vitro activities of niridazole and metronidazole against anaerobic and microaerophilic bacteria
Authors: Hof H , Sticht-Groh V , Müller K M
Published: June 2012

In vitro susceptibilities of anaerobic bacteria (Bacteroides spp., Fusobacterium spp., Clostridium spp., and Peptococcus sp.) and of Campylobacter jejuni and C. coli to niridazole and metronidazole were determined. The minimum inhibitory concentrations for niridazole ranged from 0.0037 to 1.0 microgram/ml and, for metronidazole, from 0.25 to 128 micrograms/ml.
Comparative in vitro activity of ceftriaxone against anaerobic bacteria
Authors: Rolfe R D , Finegold S M
Published: June 2012

The in vitro activity of ceftriaxone was compared with those of other recently introduced beta-lactam antimicrobial agents (cefoperazone, cefotaxime, and moxalactam) and with those of cefoxitin, clindamycin, and metronidazole against 227 strains of anaerobic bacteria. The data obtained in this investigation suggest that ceftriaxone, like a majority of the new beta-lactam antimicrobial agents, may be of limited value in the treatment of serious infections involving anaerobic bacteria.
Bruceantin, a potent amoebicide from a plant, Brucea antidysenterica
Authors: Gillin F D , Reiner D S , Suffness M
Published: June 2012

Bruceantin, purified from an Ethiopian plant used to treat dysentery, killed Entamoeba histolytica in vitro (IC50 [the concentration of drug which decreased the number of colonies to half that of controls] = 0.018 microgram/ml). Six related quassinoids of 17 tested were also amoebicidal. No relationship between quassinoid structure and amoebicidal activity was apparent.
Distribution of amoxicillin and clavulanic acid in infected animals and efficacy against experimental infections
Authors: Boon R J , Beale A S , Comber K R , Pierce C V , Sutherland R
Published: June 2012

The therapeutic effects produced by formulations of amoxicillin plus clavulanic acid (BRL 25 000A and BRL 25 000G) were compared with those of amoxicillin and clavulanic acid separately against a variety of infections produced by amoxicillin-susceptible and beta-lactamase-producing (amoxicillin-resistant) bacteria. The infection models studied included intraperitoneal infections, a mouse pneumonia, experimental pyelonephritis, and local lesions caused by Staphylococcus aureus and Bacteroides fragilis. The distribution of amoxicillin and clavulanic acid in infected animals after the administration of amoxicillin-clavulanic acid was evaluated by measurement of the concentrations of the substances present in specimens collected at the sites of infection. The results showed that both amoxicillin and clavulanic acid were well distributed in the animal body after the administration of amoxicillin-clavulanic acid formulations, being present in significant concentrations at various sites of infection, e.g., peritoneal washings, pleural fluid, pus, and infected tissue homogenates. In a number of cases, the amoxicillin concentrations measured after the administration of BRL 25000 were higher than those found after treatment with amoxicillin alone, presumably as a result of inhibition of bacterial beta-lactamases by clavulanic acid at the site of infection. The ability of clavulanic acid to protect amoxicillin in vivo was confirmed by the efficacy of amoxicillin-clavulanic acid formulations in the treatment of the infections studied, most of which were refractory to therapy with amoxicillin.
Comparative effects of 4-aminopyrazolopyrimidine, its 2'-deoxyriboside derivative, and allopurinol on in vitro growth of American Leishmania species
Authors: Avila J L , Casanova M A
Published: June 2012

When assayed on promastigotes of 10 American Leishmania isolates (including Leishmania brasiliensis and mexicana species), 4-aminopyrazolopyrimidine (AAP) was severalfold more active than allopurinol as a leishmanistatic drug. There were some intraspecific and interspecific differences among the isolates in their susceptibility to the inhibitory effects of APP and allopurinol. APP-2'-deoxyriboside did not affect the 10 isolates tested. This was surprising, because allopurinol riboside has previously been shown to be more active than allopurinol. In all of the American Leishmania isolates tested, the metabolism of [14C]6-APP resulted in a high level of HPP-ribose-5'-P and lower levels of APP-ribose-5'-P, APP-ribose-5'-PP, and APP-ribose-5'-PPP. MP, LR, LBY, and JAP isolates strongly converted APP into APP derivatives, thus perhaps explaining their greater susceptibility to the inhibitory effects of APP. With the 10 American Leishmania isolates tested, several purines reversed the inhibitory effects of allopurinol, but only adenine countered the inhibitory effects of APP. This suggests biochemical differences in the mechanisms of action of allopurinol and APP. Finally, and contrary to previous claims, the reversal by purines of the allopurinol-induced growth inhibition was not a Leishmania species-specific effect.
Ampicillin susceptibility and ampicillin-induced killing rate of Escherichia coli
Authors: Thonus I P , Fontijne P , Michel M F
Published: June 2012

The killing rate induced by ampicillin was determined in 20 strains of Escherichia coli. The apparent generation rate constant for each E. coli showed a characteristic concentration-dependent course. This course can be mathematically described and is determined by four parameters. Three of these parameters determine the speed of the process, and the fourth parameter determines a minimal concentration. The susceptibility of the strains, measured as the minimal inhibitory concentration by an agar dilution method, correlated with the minimal concentration and with a minimal inhibitory concentration calculated from the curve, but not with the rate-determining parameters.
Piperacillin pharmacokinetics in pediatric patients
Authors: Wilson C B , Koup J R , Opheim K E , Adelman L A , Levy J , Stull T L , Clausen C , Smith A L
Published: June 2012

The pharmacokinetics of piperacillin were studied in 15 pediatric patients (age range, 3.3 to 14.3 years). Piperacillin was administered in a dosage of 1.5 +/- 0.4 g/m2 (mean +/- standard deviation) every 4 to 6 h. Peak serum concentrations ranged from 69 to 354 micrograms/ml. The mean elimination half-life was 37.0 +/- 13.3 min, which is shorter than that observed in most adults with normal renal function. The mean elimination half-life in three patients with renal impairment was 60.1 +/- 12.4 min, and the mean ratio of renal clearance to total clearance was 0.57. These results suggest a significant nonrenal elimination of piperacillin. Based on these data, a dosage of 1.5 g/m2 given as a 30-min infusion every 4 h is suggested for children with normal renal function. For patients with renal impairment, the daily dosage could be calculated as follows: corrected dose = normal dose x (0.35 + [0.65 x (ClCr/0.06)]), where ClCr is the creatinine clearance expressed as liters per minute per square meter.
Antibacterial activity and beta-lactamase stability of temocillin
Authors: Jules K , Neu H C
Published: June 2012

Temocillin, a 6-alpha-methoxy penicillin, inhibited 90% of strains of Escherichia coli, Klebsiella pneumoniae, Citrobacter, Proteus, Providencia, Salmonella, and Shigella at a concentration of less than or equal to 16 micrograms/ml. Haemophilus influenzae and Neisseria gonorrhoea were inhibited by less than or equal to 1 microgram/ml. Changing the medium or pH of the cultures did not alter the minimal inhibitory concentrations, which were similar in broth and human serum, as were the minimal bactericidal concentrations. An increase in inoculum size from 10(5) to 10(7) colony-forming units increased concentration required for inhibition. Temocillin inhibited strains resistant to ampicillin, ticarcillin, cefazolin, cefamandole, and cefoxitin. Most Pseudomonas aeruginosa strains and other Pseudomonas spp. and Acinetobacter spp. were resistant, as were gram-positive organisms. Temocillin was not hydrolyzed by the common plasmid and chromosomal beta-lactamases but inhibited them. The resistance of certain gram-negative bacilli to temocillin seemed to be a result of failure of the molecule to enter through the cell wall, since combination of temocillin with EDTA made Pseudomonas, Acinetobacter, and Enterobacter strains susceptible to low concentrations of the compound.
Cefoperazone: regression analysis, disk content, and disk susceptibility testing considerations
Authors: Wright D N , Welch D F , Saxon B A , Clark S J , Matsen J M
Published: June 2012

Cefoperazone agar dilution minimal inhibitory concentration (MIC) susceptibility results were compared with zones of inhibition produced by disk diffusion susceptibility testing. Disks containing 30, 50, 75, and 100 micrograms of cefoperazone were tested for purposes of regression line comparisons and error rate-bounded analysis. Results suggest that if the MIC equivalent of susceptibility is 32 micrograms/ml, either a 50-micrograms disk with zone sizes of susceptibility (S) greater than or equal to 15 mm and resistance (R) less than or equal to 12 mm or a 75-micrograms disk with zone sizes of S greater than or equal to 17 mm and R less than or equal to 14 mm may be appropriate. If the MIC equivalent of susceptibility is 64 micrograms/ml, this would dictate use of a 75-micrograms disk with zone sizes of S greater than or equal to 17 mm and R less than or equal to 12 mm. Disks containing either less than or equal to 30 or greater than or equal to 100 micrograms of cefoperazone did not adequately discriminate among susceptible and resistant bacterial strains at either the 32- or 64-micrograms/ml MIC equivalent.
Synergistic activity of mecillinam in combination with the beta-lactamase inhibitors clavulanic acid and sulbactam
Authors: Neu H C
Published: June 2012

The beta-lactamase inhibitors clavulanic acid and sulbactam were combined with mecillinam. beta-Lactamase-containing Escherichia coli resistant to mecillinam was synergistically inhibited by both clavulanic acid and sulbactam. beta-Lactamase-containing Enterobacter was synergistically inhibited, but strains lacking beta-lactamases were not synergistically inhibited. Synergistic inhibition was noted for beta-lactamase-containing, mecillinam-resistant Klebsiella, Citrobacter, Serratia, and Salmonella isolates, but only 18% of beta-lactamase-containing Proteus mirabilis, Providencia rettgeri, Providencia stuartii, and Morganella morganii were synergistically inhibited by the combinations.
Rifampin inhibition of the occluded virus form of a nuclear polyhedrosis virus
Authors: Dougherty E M , Weiner R M , Vaughn J L , Reichelderfer C F
Published: June 2012

Rifampin at concentrations toxic to noninfected cells but not to infected cells is a selective inhibitor of occluded virus of the group A Baculoviridae (nuclear polyhedrosis virus). However, the titer of nonoccluded virus is not affected. Rifampin blocks occlusion until late in the replication cycle (14 to 16 h), and its effects are reversible. Modes of action of polyhedral inclusion body production are unknown.
Moxalactam treatment of anaerobic infections in cancer patients
Authors: Lagast H , Meunier-Carpentier F , Klastersky J
Published: June 2012

Of 30 patients with predominantly anaerobic localized infections superimposed on chronic tissue damage related to trauma, ischemia, or tumor, 22 (73%) responded satisfactorily to moxalactam therapy. Moxalactam-resistant anaerobic pathogens emerged in two patients and were responsible for treatment failure. In six patients, two of whom also acquired resistant anaerobic pathogens, isolation of moxalactam-resistant aerobic pathogens increased during therapy.
Differences in susceptibilities of species of the Bacteroides fragilis group to several beta-lactam antibiotics: indole production as an indicator of resistance
Authors: Jenkins S G , Birk R J , Zabransky R J
Published: June 2012

Clinical isolates of the members of the Bacteroides fragilis group differ markedly in their susceptibilities to a variety of beta-lactam antibiotics, including cefoperazone, moxalactam, cefotaxime, cefoxitin, cefamandole, cephalothin, cefazolin, and carbenicillin, as determined by dilution techniques. The minimum concentrations required to inhibit at least 50% of the strains tested (MIC50) for the entire B. fragilis group were lowest with moxalactam and cefoxitin, 4 and 8 micrograms/ml, respectively, whereas the MIC90S of cefoperazone, cefotaxime, moxalactam, cefoxitin, and carbenicillin were equivalent (64 micrograms/ml); the MIC90S of cefamandole, cephalothin, and cefazolin were higher. Indole-positive members of the group (B. ovatus, B. thetaiotaomicron, and B. uniformis) were significantly more resistant to every antibiotic tested than were indole-negative members (B. fragilis, B. distasonis, and B. vulgatus). In a 6-month survey of clinical laboratory data, indole-positive strains comprised 40% of the B. fragilis group isolates and 22% of all Bacteroides isolates; B. fragilis was the most common species isolated (23%). The increased use of second-generation and the introduction of third-generation cephalosporins may dictate that clinical microbiology laboratories routinely identify members of the B. fragilis group as to species or, alternatively, test for indole production in addition to performing more extensive susceptibility testing.
Antiviral activity and mechanism of action of 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860)
Authors: Torney H L , Dulworth J K , Steward D L
Published: June 2012

A nitrobenzene derivative, MDL-860, was found to inhibit plaque formation, cytopathic effect, or both in 11 of 12 picornaviruses at concentrations which did not affect cell growth. The compound did not directly inactivate the virus. MDL-860 inhibited actinomycin D-resistant [3H]uridine uptake in cells infected with coxsackievirus A21 or rhinovirus 1-A, whereas incorporation into uninfected cells was not inhibited. With three picornaviruses (echovirus type 12, poliovirus type 2, and rhinovirus type 1-A) made photosensitive with neutral red, MDL-860 did not appear to cause a significant reduction in their loss of photosensitivity (uncoating) during the first 3 h of infection. MDL-860 appears to inhibit some early event in virus replication, after uncoating, which is required for synthesis of a majority of viral RNA.
Tetracycline-resistant L-forms isolated from an antibiotic-susceptible strain of Listeria monocytogenes
Authors: Schmitt-Slomska J , Marmouset M C , Louis C , Bally R , Starka G , Madoff S
Published: June 2012

A tetracycline-susceptible strain of Listeria monocytogenes type 4b was converted to stable L-forms by penicillin. L-form variants resistant to tetracycline were then selected from a predominantly tetracycline-susceptible L-form population on plates containing penicillin and increasing concentrations of tetracycline. The origin of tetracycline-resistant L-forms from the parent Listeria strain was confirmed biochemically, by immunofluorescence, and by polyacrylamide gel electrophoresis. Scanning and transmission electron microscopy confirmed the typical L-form structure and the complete lack of cell wall in both L-form strains. The level of [3H]tetracycline uptake was lower in tetracycline-resistant than in susceptible cells.
Inhibition of RNA Viruses In Vitro and in Rift Valley Fever-Infected Mice by Didemnins A and B
Authors: Canonico Peter G. , Pannier Wallace L. , Huggins John W. , Rienehart Kenneth L.
Published: June 2012

Didemnins, a new class of depsipeptides isolated from a Caribbean tunicate, have been shown to have potent antiviral activity against a broad range of RNA viruses in vitro. Didemnins A and B both protected mice against a lethal challenge of Rift Valley fever virus.