Antimycobacterial evaluation of Peruvian plants.

We present the results of an antimycobacterial screening of 270 Peruvian plant samples representing 216 species from 171 genera in 63 families. Dichloromethane extracts were tested at a concentration of 50 microg/ml for inhibition of Mycobacterium tuberculosis in radiometric culture. Slightly more than half of the samples tested showed inhibition of M. tuberculosis at this concentration.

Extracts of spice and food plants from Thai traditional medicine inhibit the growth of the human carcinogen Helicobacter pylori.

BACKGROUND: Helicobacter pylori (HP) is a gramnegative bacterium and well recognized as being the primary etiological agent responsible for the development of gastritis, dyspepsia, peptic ulcer disease and gastric cancer. In developing countries, a high prevalence of HP infection is associated with an increased incidence of gastric cancer. Thailand, however, while having a high prevalence of HP infections, has a lower than expected gastric cancer rate than other developing countries. It has been suggested that the diet and life style in Thailand may explain this discrepancy. MATERIALS AND METHODS: The in vitro susceptibility of 18 strains of HP to 20 extracts of spice and food plants used in Thai traditional medicine for the treatment of GI disorders was assessed. RESULTS: Methanol extracts of Myristica fragrans (aril) inhibited the growth of all HP strains with minimum inhibitory concentration (MIC) of 12.5 micrograms/ml; extracts from Barringtonia acutangula (leaf) and Kaempferia galanga (rhizome) had an MIC of 25.0 micrograms/ml; Cassia grandis (leaf), Cleome viscosa (leaf), Myristica fragrans (leaf) and Syzygium aromaticum (leaf) had MICs of 50.0 micrograms/ml. Extracts with an MIC of 100.0 micrograms/ml included Pouzolzia pentandra (leaf), Cycas siamensis (leaf), Litsea elliptica (leaf) and Melaleuca quinquenervia (leaf). CONCLUSION: Plants used in Thai traditional medicine to treat gastrointestinal ailments inhibit the growth of HP. These data indicate that these plants may have chemopreventative activities and thus may partly explain the reduced incidence of gastric cancer in Thailand.

Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen.

BACKGROUND: Curcumin, a polyphenolic chemical constituent derived from turmeric (Curcuma longa), has been shown to prevent gastric and colon cancers in rodents. Many mechanisms have been proposed for the chemopreventative effects, although the effect of curcumin on the growth of Helicobacter pylori has not been reported. H. pylori is a Group 1 carcinogen and is associated with the development of gastric and colon cancer. MATERIALS AND METHODS: A methanol extract of the dried powdered turmeric rhizome and curcumin were tested against 19 strains of H. pylori, including 5 cagA+ strains. RESULTS: Both the methanol extract and curcumin inhibited the growth of all strains of H. pylori in vitro with a minimum inhibitory concentration range of 6.25-50 micrograms/ml. CONCLUSION: These data demonstrate that curcumin inhibits the growth of H. pylori cagA+ strains in vitro, and this may be one of the mechanisms by which curcumin exerts its chemopreventative effects.

Postantibiotic effects of ABT-773 and amoxicillin-clavulanate against Streptococcus pneumoniae and Haemophilus influenzae.

This study determined the postantibiotic effect (PAE) of ABT-773 versus that of amoxicillin-clavulanate against clinical isolates of Streptococcus pneumoniae and Haemophilus influenzae. The PAEs of ABT-773 and amoxicillin-clavulanate ranged from 2.3 to 6.0 h and 0 to 2.2 h against S. pneumoniae and from 2.7 to 9.1 h and 0 to 0.8 h against H. influenzae, respectively.

Antimicrobial-coated/bonded and -impregnated intravascular catheters.

OBJECTIVE: To review the literature regarding the prevention of catheter colonization and catheter-related bloodstream infections (CRBIs) with the use of antimicrobial-coated/bonded and -impregnated intravascular catheters. DATA SOURCES: Primary and review English-language literature were identified using MEDLINE (1966-September 2000) pertaining to the key terms antibiotic, antimicrobial, antiseptic, silver, and bonded, coated, Impregnated catheters. In addition, textbooks and relevant reference lists were reviewed. DATA EXTRACTION: All articles identified through the data sources were evaluated. Information deemed relevant to the objectives of the review was included. DATA SYNTHESIS: Significant morbidity and mortality are associated with the development of CRBIs. Preventative measures such as modification of these catheters with antimicrobial coating/bonding have produced varying results. Trials evaluating cefazolin, teicoplanin, vancomycin, silver, and chlorhexidine-silver sulfadiazine (C-SS) used for coated/bonded intravascular catheters have not demonstrated a consistent decrease in the incidence of CRBIs. However, a meta-analysis of trials evaluating C-SS intravascular catheters demonstrated a statistically significant reduction in CRBIs. A larger reduction in CRBIs has been reported with minocycline-rifampin (M-R) versus C-SS intravascular catheters. Use of the M-R and C-SS catheters may result in a cost savings of $100 million and reduce as many as 12,000 CRBI-related deaths annually when used short term (<7 d). CONCLUSIONS: When used for short-term catheterization, M-R catheters appear to be superior to the currently available C-SS catheters at preventing CRBIs. Significant cost savings and reduction in mortality can be anticipated with the use of M-R catheters.

Cunninghamella bertholletiae infection in a bone marrow transplant patient: amphotericin lung penetration, MIC determinations, and review of the literature.

Infections caused by Cunninghamella bertholletiae, an opportunistic fungal organism, have an extremely high mortality rate. A fatal case of C. bertholletiae fungal pneumonia occurred in a man who had received an allogeneic bone marrow transplant. Aggressive debridement and high-dose liposomal amphotericin B failed to eradicate the infection. Right lung tissue samples obtained during lobectomy were assayed for amphotericin B concentrations by high-performance liquid chromatography, and minimum inhibitory concentration (MIC) determinations of amphotericin B against C. bertholletiae were determined by the macrobroth dilution method. The MIC for the isolate of C. bertholletiae was 4 microg/ml. Amphotericin B lung concentrations averaged 9.5 microg/ml (range 3.7-13.8 microg/ml), with a corresponding serum trough concentration of 0.9 microg/ml. To our knowledge, this is the first reported case of amphotericin B concentrations measured at the site of infection in a patient with a pulmonary Cunninghamella infection, together with a corresponding MIC of the organism. The patient's death, which occurred despite aggressive debridement and high amphotericin B lung concentrations, highlights the need for novel strategies to treat infections caused by invasive molds such as C. bertholletiae.

In vitro activities of a new ketolide, ABT-773, alone and in combination with amoxicillin, metronidazole, or tetracycline against Helicobacter pylori.

The in vitro activity of ABT-773, a new ketolide, was compared with those of clarithromycin, amoxicillin, metronidazole, and tetracycline against 15 strains of Helicobacter pylori. The MIC of ABT-773 at which 90% of isolates were inhibited was 0.25 microg/ml, which was 3 dilutions higher than that of the most active agent, clarithromycin. Synergy and antagonism were not seen with any combinations. Additive activity was seen with tetracycline, metronidazole, and amoxicillin in 100, 60, and 40% of the combinations, respectively.

Postantibiotic effects and bactericidal activities of clarithromycin-14-hydroxy-clarithromycin, versus those of amoxicillin-clavulanate, against anaerobes.

The bactericidal activities and postantibiotic effects (PAE) of clarithromycin-14-hydroxy-clarithromycin and amoxicillin-clavulanate against Bacteroides fragilis and Peptostreptococcus anaerobius were determined. A concentration of twice the MIC resulted in bactericidal activity against four of four and three of four organisms at 24 h with clarithromycin-14-hydroxy-clarithromycin and amoxicillin-clavulanate, respectively. The PAE of clarithromycin-14-hydroxy-clarithromycin was 1.44 to 3.20 h, compared to the less than 1 h of amoxicillin-clavulanate. Clarithromycin-14-hydroxy-clarithromycin possesses good activity against susceptible anaerobes.

Modified time-kill assay against multidrug-resistant Enterococcus faecium with novel antimicrobial combinations.

This study used a modified time-kill assay to compare the in-vitro activity of chloramphenicol and quinopristin/dalfopristin combined with vancomycin, ampicillin or gentamicin against multidrug-resistant Enterococcus faecium. The assay uses standardized time-kill methods with the following modifications: centrifugation of the test tubes at 1-2 h intervals, removal of supernatant and resuspension of bacteria in media containing antibiotic concentrations corresponding to simulated steady-state serum concentrations. None of the agents, alone or in combination, produced bactericidal or synergic activity. The modified time-kill assay more closely simulates in-vivo conditions and may provide a better qualitative assay to determine the interaction between antimicrobial agents and bacteria.

Bactericidal activity and postantibiotic effect of levofloxacin against anaerobes.

The bactericidal activity and postantibiotic effect (PAE) of levofloxacin against nine anaerobes were determined. Levofloxacin at concentrations of the MIC and twice the MIC was bactericidal at 24 h to five of nine and nine of nine strains, respectively. The PAE of levofloxacin following a 2-h exposure ranged from 0.06 to 2.88 h.

In-vitro synergy of paromomycin with metronidazole alone or metronidazole plus hydroxymetronidazole against Helicobacter pylori.

The in-vitro activities of paromomycin and metronidazole alone or paromomycin and metronidazole plus hydroxymetronidazole (2:1 ratio) were studied against 19 Helicobacter pylori isolates using an in-vitro chequerboard technique. Partial synergy was demonstrated for the majority of isolates (11/19) for both combinations tested. When hydroxymetronidazole was added to the parent compound, the number of metronidazole-sensitive isolates demonstrating synergy increased to 5/12, compared with 1/12 for the combination that did not include the metabolite. In metronidazole-resistant isolates there was a shift from an additive effect to partial synergy for the combination containing hydroxymetronidazole. The in-vitro activity of paromomycin and the synergic effect that is achieved in combination with metronidazole and hydroxymetronidazole render paromomycin suitable for further investigation as a treatment option for H. pylori infection.

In vitro activity of RPR 106972 alone and in combination with vancomycin, ampicillin, and gentamicin against multidrug-resistant enterococci.

This investigation used checkerboard and time-kill assays to evaluate the in vitro activity of RPR 106972 (45% pristinamycin IB and 55% pristinamycin IIB) alone and in combination with vancomycin or ampicillin +/- gentamicin against multidrug-resistant enterococci. The checkerboard procedure resulted in synergistic or additive effects in 91% of the isolates with the combination of RPR 106972 plus vancomycin versus 68% with RPR 106972 plus ampicillin. The addition of gentamicin to either combination resulted in synergistic or additive results in 100% of the isolates. Inhibitory activity was observed with the time-kill assay with mean change in log10 CFU/mL at 24 h of -0.31 for RPR 106972, 3.3 for vancomycin, -0.46 for RPR 106972 plus vancomycin, and -0.35 for RPR 106972 plus vancomycin and gentamicin. No antagonism was noted with any of the combinations. RPR 106972 demonstrates good inhibitory activity against Enterococcus faecium and may prove useful in the treatment of enterococcal infections.

Bactericidal activity and postantibiotic effect of clarithromycin and 14-hydroxyclarithromycin, alone and in combination, against Legionella pneumophila.

Time-kill curves using simulated peak and trough serum concentrations, and postantibiotic effect (PAE) were determined for clarithromycin and 14-hydroxyclarithromycin alone and in combination against four strains of Legionella pneumophila. Both compounds were bactericidal at both peak and trough concentrations. The combination at trough concentrations demonstrated lower killing activity than the parent drug in three of the four strains. PAE ranges were 7.28-17.3 h for clarithromycin, 6.78-14.77 h for the metabolite, and 5.15-13.23 h for the combination.

Levofloxacin and sparfloxacin: new quinolone antibiotics.

OBJECTIVE: To discuss the pharmacology, pharmacokinetics, spectrum of activity, clinical trials, and adverse effects of levofloxacin and sparfloxacin, two new fluoroquinolone antibiotics. DATA SOURCES: Literature was identified by a MEDLINE search from January 1985 to September 1997. Abstracts and presentations were identified by review of program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy from 1988 to 1996. STUDY SELECTION: Randomized, controlled clinical studies were selected for evaluation; however, uncontrolled studies were included when data were limited for indications approved by the Food and Drug Administration (FDA). In vitro data were selected from comparison trials whenever available. Only in vitro trials that provided data on the minimum inhibitory concentrations required to inhibit 90% of isolates were used. Data from North American studies were selected whenever available. DATA EXTRACTION: Data were evaluated with respect to in vitro activity, study design, clinical and microbiologic outcomes, and adverse drug reactions. DATA SYNTHESIS: Levofloxacin and sparfloxacin are active against pathogens frequently involved in community-acquired upper and lower respiratory tract infections, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae. Both compounds have enhanced activity compared with ciprofloxacin against most gram-positive bacteria, including enterococci, streptococci, and staphylococci, and retain good activity against most Enterobacteriaceae and Pseudomonas aeruginosa. Sparfloxacin has greater anaerobic activity than levofloxacin, which is more active than ciprofloxacin or ofloxacin. Although many clinical studies are available only in abstract form, the clinical data demonstrate that these new quinolones are effective for most community-acquired upper and lower respiratory tract infections, urinary tract infections, gonococcal and nongonococcal urethritis, and skin and skin structure infections. FDA-approved indications are limited for both compounds to date. CONCLUSIONS: Levofloxacin and sparfloxacin have improved gram-positive activity compared with that of older fluoroquinolones, and are administered once daily. Sparfloxacin-associated photosensitivity may limit its therapeutic usefulness. Clinical trials confirm that these agents are as effective as traditional therapies for the management of community-acquired pneumonia, acute exacerbations of chronic bronchitis, sinusitis, urinary tract infections, acute gonococcal and nongonococcal urethritis, and skin and skin structure infections.

In vitro activity of clarithromycin alone and in combination with ciprofloxacin or levofloxacin against Legionella spp.: enhanced effect by the addition of the metabolite 14-hydroxy clarithromycin.

Clarithromycin is metabolized to an active metabolite, 14-hydroxy clarithromycin. These compounds have demonstrated excellent in vitro activity against Legionella species, with both agents having significantly lower MICs than erythromycin. Using a checkerboard assay, the activity of clarithromycin and its hydroxy metabolite, alone and in combination, was examined against 41 Legionella organisms. The activity of clarithromycin and 14-hydroxy clarithromycin, in a 2:1 ratio, plus ciprofloxacin or levofloxacin was also determined. Activity of the antibiotic combinations was determined by calculating the fractional inhibitory concentration index. An agar dilution method using buffered charcoal yeast extract media was used for susceptibility and synergy testing. An inoculum of 10(4) CFU/spot was used, with all plates incubated at 35 degrees C for 48 h. The MIC90 for clarithromycin or 14-hydroxy clarithromycin alone was 0.5, versus 0.25 microgram/mL for the combination. Additive effects were observed with clarithromycin and its hydroxy metabolite for 61% of the Legionella species, with fractional inhibitory concentration indices ranging from 0.63 to 1.25. The 14-hydroxy metabolite significantly increased the activity of both fluoroquinolone/clarithromycin combinations. Based on these data, in vitro susceptibility testing of agents such as clarithromycin should be reevaluated to account for the activity of active metabolites.