Trimethoprim and methenamine hippurate. A new theoretical combination for the treatment of urinary tract infections

The antibacterial interaction of methenamine hippurate (MH) and trimethoprim (TMP) was tested in vitro in 3 different media: urine, brain-heart broth and Mueller-Hinton broth. MH and TMP were found to have a synergistic interaction in chequer-board titration against 11/11 bacteria in urine. Low concentrations of MH (1/2 MIC) had an additive or synergistic effect with TMP against 14/14 bacteria in brain-heart broth and 20/26 bacteria in Mueller-Hinton broth. In addition, the growth of bacteria in urine from healthy subjects treated with TMP (200 mg), MH (1000 mg) or a combination of TMP + MH (200 + 1000 mg) twice a day for 5 days was compared. A synergistic or additive effect of TMP and MH was found against 14/16 strains. Antagonistic interaction was not found in any of the tests. Preliminary pharmacokinetic studies with TMP and MH showed no marked interaction between the drugs. The hydrolysis of MH to formaldehyde was inversely related to urinary pH, and at pH 5 most of the formaldehyde released from MH in urine was generated within 3 h. The results suggest that the combination of TMP and MH may be more efficient than TMP alone in the treatment of urinary tract infections.     

Further observations on the potentiation of the antibacterial effect of methenamine by acetohydroxamic acid.

The use of methenamine in the treatment of urinary tract infections due to Proteus species is limited by urine alkalinity. Acetohydroxamic acid, an inhibitor of urease, maintains acidity despite growth of Proteus in urine. Easily achievable concentrations of acetohydroxamic acid in vitro systems that simulated the dynamics of the urinary tract potentiated the antibacterial effect of methenamine against Proteus species. The combined use of a urease inhibitor and methenamine may be effective in the treatment of urinary infection caused by these organisms.     

河南蜂胶对白色念珠菌的抑菌作用研究

目的探讨河南蜂胶对白色念珠菌的抑菌效果。方法采用琼脂平板扩散法,以白色念珠菌为实验菌种,设置不同pH平板实验组和不同的蜂胶浓度组,每组重复3次,每张滤纸片(直径6mm)加样7μl,观察48h的抑菌效果。结果河南蜂胶在pH5.5、6.0、6.5、7.0、7.5、8.0、8.5条件下对白色念珠菌的抑菌环直径(mm)分别为:9.08±0.80、11.25±0.43、11.42±0.63、12.58±0.29、15.25±0.43、21.50±0.87、29.00±0.50;蜂胶浓度从15.50%～0.12%蜂胶组及空白对照组的抑菌环直径(mm)依次为:25.50±0.50、22.25±0.43、18.67±0.76、15.83±0.58、10.33±1.04、8.50±0.00、7.25±0.25、0、0、0。结论河南蜂胶对白色念珠菌的抑菌活性随蜂胶浓度和pH的降低而减弱,可观察到抑菌环的最低蜂胶浓度为0.25%。     

Ceftizoxime (FK 749) in vitro antibacterial activity

Summary The minimal inhibitory concentrations of ceftizoxime, cefotaxime, moxalactam, cefoperazone, cefotiam and cefamandole were determined against various species of gram-negative bacteria and againstStaphylococcus aureus. Ceftizoxime was more active againstEnterobacteriaceae than cefamandole, cefotiam and cefoperazone and slightly more active than or similar to moxalactam and cefotaxime. Like cefotaxime and moxalactam, ceftizoxime was less active than cefoperazone againstPseudomonas aeruginosa and less active than cefamandole againstS. aureus. Ceftizoxime was active against cephalosporinase-producingEnterobacteriaceae with a mean MIC of 0.19 mg/l. However, some isolates had an MIC above 32 mg/l.

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Antibakterielle In vitro-Aktivität von Ceftizoxim (FK 749)

Zusammenfassung Die minimalen Hemmkonzentrationen von Ceftizoxim, Cefotaxim, Moxalactam, Cefoperazon, Cefotiam und Cefamandol gegen verschiedene Spezies gramnegativer Bakterien und gegenStaphylococcus aureus wurden bestimmt. GegenEnterobacteriaceae war Ceftizoxim wirksamer als Cefamandol, Cefotiam und Cefoperazon, geringfügig wirksamer als Moxalactam und Cefotaxim oder von ähnlicher Aktivität wie die beiden letztgenannten Substanzen. Wie Cefotaxim und Moxalactam besaß Ceftizoxim geringere Aktivität gegenüberPseudomonas aeruginosa als Cefoperazon; außerdem war Ceftizoxim gegenS. aureus weniger wirksam als Cefamandol. Ceftizoxim erwies sich als wirksam gegenüber Cephalosporinase bildendenEnterobacteriaceae bei mittleren MHK-Werten von 0,19 mg/l; bei manchen Isolaten lagen jedoch die MHK-Werte über 32 mg/l.

     

In vitro antibacterial activity of Desmodium gangeticum (L.) DG

ObjectiveTo identify the antibacterial activity of Desmodium gangeticum (D. gangeticum).MethodsAntibacterial activity of D. gangeticum was tested with various solvents viz., methanol, ethanol, chloroform and aqueous extract against various bacterial pathogens such as Klebsiella pneumoniae, Escherichia coli, Salmonella typhi, Streptococcus mutants and Pseudomonas aeruginosa. Antibiotic sensitivity assay was performed with amoxicillin, kanamycin, tetracyclin, ciprofloxacin and penicillin.ResultOf the selected several extract, the methanolic extract showed maximum zone of inhibition (24±2.3mm) against S. mutants and minimum zone of inhibition was observed with aqueous extract against P. aeruginosa (7±0.08). In addition the antibiotic sensitivity was observed with kanamycin, tetracyclin, ciprofloxacin against all bacterias.ConclusionsThe methonalic extract of D. gangeticum be able to use as potential antibacterial source for various infective pathogens.     

Comparison of the antibacterial activity of norfloxacin (MK 0366, AM 715), a new organic acid,with that of other orally absorbed chemotherapeutic agents

Summary 425 randomly selected, fresh clinical isolates were tested for susceptibility to norfloxacin and other orally absorbed agents, i. e. amoxicillin, ampicillin, carbenicillin (available commercially as the indanyl ester), cefaclor, cinoxacin, erythromycin, nalidixic acid, penicillin G, tetracycline, trimethoprim and co-trimoxazole. The results have shown norfloxacin to be the most potent agentin vitro against representative members of the familyEnterobacteriaceae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter spp.,Neisseria gonorrhoeae andHaemophilus influenzae. Ninety percent of the isolates in these groups of bacteria were inhibited by less than 1 mg/l, 2 mg/l, 8 mg/l, 32 mg/l, 0.06 mg/l and 0.25 mg/l of norfloxacin, respectively. Although norfloxacin inhibited most streptococci andUreaplasma at a concentration of 8 mg/l or less, penicillin G proved to be the most active againstStreptococcus pygenes andStreptococcus pneumoniae; trimethoprim was the most active againstStreptococcus faecalis, and tetracycline the most active againstUreaplasma.

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Vergleich der antibakteriellen Aktivität von Norfloxacin (MK 0366, AM 715), einer neuen organischen Säure, mit derjenigen von anderen, bei oraler Applikation resorbierbaren Chemotherapeutika

Zusammenfassung 425 zufallsgemäß ausgewählte, frische klinische Isolate wurden auf ihre Empfindlichkeit gegenüber Norfloxacin und anderen nach oraler Gabe resorbierbaren Substanzen, wie Amoxicillin, Ampicillin, Carbenicillin (kommerziell als Indanylester erhältlich), Cefaclor, Cinoxacin, Erythromycin, Nalidixinsäure, Penicillin G, Tetracyclin, Trimethoprim und Co-Trimoxazol, getestet. Die Ergebnisse zeigten, daß Norfloxacinin vitro die wirksamste Substanz gegen repräsentative Mitglieder der FamilieEnterobacteriaceae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter spp.,Neisseria gonorrhoeae undHaemophilus influenzae ist; 90% der Isolate dieser Gruppen von Bakterien wurden durch Norfloxacin in Konzentrationen von weniger als 1 mg/l; 2 mg/l; 8 mg/l; 32 mg/l; 0,06 mg/l und 0,25 mg/l gehemmt. Norfloxacin hemmte zwar die meisten Streptokokken undUreaplasma Stämme bei einer Konzentration von 8 mg/l oder weniger, doch erwies sich Penicillin G als die wirksamste Substanz gegenüberStreptococcus pyogenes undStreptococcus pneumoniae, Trimethoprim war am aktivsten gegenStreptococcus faecalis und Tetracyclin wies die stärkste Aktivität gegenUreaplasma auf.

     

Probenecid and the antibacterial activity of cephradine in vivo.

The influence of probenecid on the concentrations in blood and antibacterial efficacy of cephradine was studied in experimentally infected mice. An infection was induced by injection of 5 X 10(6) Escherichia coli into the thighs of irradiated, granulocytopenic mice. Probenecid was given 1 hr later, just before the administration of cephradine. The control animals received only the vehicle. Concentrations of cephradine in blood were determined for 2 hr; the antibacterial activity was estimated from bacterial counts made in the homogenized individual thighs. The blood concentrations of cephradine were 1.77 times higher in the probenecid-treated animals than in the controls. The potency ratio for doses was 2.41, the potency ratio for the areas under the drug concentration in blood vs. time curves was 1.34, and that for the peak blood concentrations was 1.43.     

Radical scavenging and antibacterial activity of Arnebia benthamii methanol extract

ObjectiveTo evaluate in vitro antioxidant and antibacterial activity of methanolic extract of Arnebia benthamii (A. benthamii) whole plant.MethodsPlasmid damage was analyzed by agarose gell electrophoresis. Calf thymus DNA was monitored by TBARS formation. DPPH, reducing power and lipid peroxidation was evaluated by using standard procedures. Antibacterial assay was monitored by disc diffusion method.ResultsDPPH radical scavenging and hydroxyl radical scavenging potential of the plant revealed that the extract to be active radical scavenger. Reducing (Fe³⁺-Fe²⁺) power and lipid peroxidation inhibition efficiency (TBARS assay) of the extract was also evaluated and the extract showed promising activity in preventing lipid peroxidation and might prevent oxidative damages to biomolecules. The extract offered a significant protection against plasmid and calf thymus DNA damage induced by hydroxyl radicals. The extract was also evaluated on different bacterial strains and the maximum antibacterial activity was exhibited against Escherichia coli (E. coli) when compared with standard drug.ConclusionsThese findings demonstrate that the methanol extract of A. benthamii has excellent anti-oxidant activities and could be considered as a potential source of lead molecules for pharmaceutical industries.     

In vitro antituberculosis activity of a new antibacterial substance ofloxacin (DL8280)

A new antituberculosis agent, ofloxacin (DL8280), inhibited the growth of Mycobacterium tuberculosis at concentrations of 0.63 to 1.25 micrograms/ml. There were no cross-resistance relationships between this agent and other antituberculosis agents. The agent delayed the growth rate of M. tuberculosis (strain H37Rv) at concentrations of 0.2 to 0.5 microgram/ml. It showed considerable bactericidal activity at concentrations a little higher than the growth-inhibitory concentration. The combined effect with other antituberculosis agents seemed to be additive. The pattern of resistance that developed with this agent was the obligatory two-step pattern, and there were 2 resistant phenotypes.     

Cefpodoxime: Comparative antibacterial activity,influence of growth conditions,and bactericidal activity

Summary The antimicrobial activity of cefpodoxime, the active metabolite of the new cephalosporin ester cefpodoxime proxetil, in comparison to cefixime, cefotiam, cefuroxime, and cefotaxime was determined against a broad spectrum of freshly isolated gram-positive and gram-negative bacterial strains. Cefpodoxime was demonstrated to be inhibitory at concentrations of 1 mg/l against 90% of strains ofMoraxella catarrhalis, Haemophilus influenzae, Escherichia coli (-lactamase- negative strains),Klebsiella spp.,Serratia spp.,Proteus mirabilis, Proteus vulgaris, Providencia spp., andSalmonella spp. This antimicrobial activity of cefpodoxime was generally superior to that of cefuroxime and similar to that of cefixime. Cefpodoxime was active at 1 mg/l against 50% of the members of -lactamase-producingEscherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter spp., andMorganella morganii. Cefpodoxime proved to be highly inhibitory against group A, B, and G streptococci andStreptococcus pneumoniae (MIC₉₀ < 0.015 mg/l). The MICs of cefpodoxime and those of the other cephalosporins were <2 mg/l for 90% of the strains ofStaphylococcus aureus andStaphylococcus epidermidis, with the exception of cefixime which had no activity with MICs below 8 mg/l against these bacteria.Pseudomonas spp.,Acinetobacter spp., andEnterococcus spp. were resistant to cefpodoxime. The antibacterial activity of cefpodoxime was only to a minor degree influenced by different growth conditions with the exception of high inoculum sizes against some -lactamase producing strains of gramnegative bacilli. In view of the reportedin vitro antimicrobial activity of cefpodoxime, its prodrug cefpodoxime proxetil after oral administration is expected to be very useful for the treatment of patients with respiratory and urinary tract infections.

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Cefpodoxim: Vergleichende In-vitro-Aktivität, Einfluß von Wachstumsbedingungen und Bakterizidie

Zusammenfassung Die antimikrobielle Aktivität von Cefpodoxim, dem aktiven Metaboliten des neuen Cephalosporin-Esters Cefpodoxim-Proxetil, wurde im Vergleich mit Cefixim, Cefotiam, Cefuroxim und Cefotaxim gegen ein breites Spektrum frisch isolierter grampositiver und gramnegativer Bakterienstämme untersucht. Cefpodoxim zeigte sich bei Konzentrationen 1 mg/l aktiv gegen 90% der Stämme vonMoraxella catarrhalis, Haemophilus influenzae, Escherichia coli (-laktamase-negative Stämme),Klebsiella spp.,Serratia spp.,Proteus mirabilis, Proteus vulgaris, Providencia spp. undSalmonella spp. Diese antimikrobielle Aktivität von Cefpodoxim war im allgemeinen der von Cefuroxim überlegen und mit der von Cefixim vergleichbar. Cefpodoxim war in einer Konzentration von 1 mg/l aktiv gegen 50% der Isolate -laktamase-bildenderEscherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter spp. undMorganella morganii. Cefpodoxim erwies sich als hochaktiv gegen Streptokokken der Gruppen A, B und G und gegenStreptococcus pneumoniae (MHK₉₀-Werte < 0,015 mg/l). Die MHK-Werte von Cefpodoxim und die der anderen Cephalosporine betrugen 2 mg/l für mindestens 90% der Stämme vonStaphylococcus aureus undStaphylococcus epidermidis, mit der Ausnahme von Cefixim, das keine Aktivität gegen diese Erreger hatte (MHK-Werte > 8 mg/l).Pseudomonas spp.,Acinetobacter spp. undEnterococcus spp. waren gegen Cefpodoxim resistent. Die antibakterielle Aktivität von Cefpodoxim wurde durch verschiedene Wachstumsbedingungen nur wenig beeinflußt, eine Ausnahme bildeten hohe Inokulum-Größen bei einigen -laktamase-bildenden Stämmen von gramnegativen Stäbchen. Angesichts der beschriebenen antimikrobiellen Aktivität von Cefpodoxim ist zu erwarten, daß sein oral anwendbares Prodrug Cefpodoxim-Proxetil bei der Behandlung von Patienten mit Atemwegs- und Harnwegsinfekten sehr nützlich sein wird.

     

The antibacterial activity of combinations of mecillinam and ampicillin in vitro and in normal and granulopenic mice

The antibacterial activity of mecillinam and ampicillin, alone and in combination, against Escherichia coli was quantitated and compared in vitro and in vivo. Minimum inhibitory concentrations (MICs) were determined for both antibiotics individually and combined. Two-hour growth curves were established in vitro. A quadratic fit to these growth curves provided quantitative concentration-dependent growth characteristics. The antibacterial activity in vivo was determined by applying a short-term thigh muscle infection model to normal and irradiated granulopenic mice. The effects in vivo were also quantitated as dose-dependent or concentration-dependent parameters. Mecillinam showed activity in vitro, but none in vivo. Combinations of mecillinam with ampicillin showed a strong potentiation, as judged from MICs and from short-term experiments in vitro and in the normal and irradiated granulopenic mice. The potentiating activity in vivo was not influenced by host factors (i.e. granulocytes). However, the degree of potentiation indicated by the MICs led to strong overestimation of the effect of the combination of the two antibiotics on short-term in vitro growth. Furthermore, the combined activity in vitro overestimated the potentiating effect of the two antibiotics in vivo.