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1.  In vitro susceptibilities of Aeromonas hydrophila against new antibiotics. 
The antibiotic susceptibilities of 16 clinical isolates of Aeromonas hydrophila obtained from cancer patients with septicemia were studied. Of the new beta-lactam antibiotics tested, azthreonam and moxalactam were the most active, followed by cefoperazone, cefotaxime, and ceftizoxime. Excellent activity was demonstrated by chloroamphenicol, tetracycline, aminoglycosides, and trimethoprim-sulfamethoxazole. Semisynthetic penicillins had no appreciable activity against this organism.
PMCID: PMC183774  PMID: 7137987
2.  In vitro susceptibility of Xanthomonas (Pseudomonas) maltophilia to newer antimicrobial agents. 
The susceptibilities of 45 clinical and 3 environmental isolates of Xanthomonas maltophilia to 14 antimicrobial agents was determined by broth microdilution. The newer quinolones PD117596, PD117558, PD127391, A-56620, amifloxacin, and fleroxacin were the most active agents tested, with 70 to 99% of isolates being susceptible to these agents. All isolates were resistant to trospectomycin. The new aminoglycosides SCH24120 and SCH22591 were active against 12 and 1% of isolates, respectively.
PMCID: PMC171884  PMID: 2221872
3.  In vitro activity of WIN 49375 compared with those of other antibiotics in isolates from cancer patients. 
The activity of WIN 49375 [6-fluoro-1, 4-dihydro-1-(methylamino)-7-(4-methyl-1-piperazinyl)-4-oxo-3- quinolinecarboxylic acid], a new synthetic quinolone, was tested in vitro against 587 clinical isolates. The MICs for 90% of isolates of Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae were 0.20, 1.56, and 0.39 microgram/ml, respectively. The MICs for 90% of isolates of Pseudomonas aeruginosa and Serratia marcescens were both 3.12 micrograms/ml. WIN 49375 was minimally active against gram-positive cocci. Its in vitro activity suggests that it may be useful for the treatment of gram-negative bacillary infections.
PMCID: PMC176185  PMID: 6508271
4.  Piperacillin plus vancomycin in the therapy of febrile episodes in cancer patients. 
Piperacillin and vancomycin were used as initial empirical therapy for 211 febrile episodes in cancer patients. The response rate in 95 episodes of documented infection was 72%. The response of bacteremias, soft tissue infections, and pneumonias was 78, 71, and 38%, respectively. The response in infections caused by gram-negative organisms was 73%. Only 6 of 10 Pseudomonas aeruginosa infections responded to therapy, although the organisms were sensitive in vitro to piperacillin. Of 14 infections caused by gram-positive organisms, 12 responded to this combination. No major side effects were observed with this regimen. Although the overall response rate with this antibiotic combination was comparable with other regimens used for neutropenic patients, superior results might be obtained by combining piperacillin with an extended-spectrum cephalosporin or an aminoglycoside.
PMCID: PMC176155  PMID: 6508260
5.  Effect of systemic antimicrobial prophylaxis on microbial flora. 
Fifteen patients undergoing intensive chemotherapy for oat cell carcinoma of the lung in a protected environmental unit received antimicrobial prophylaxis with oral trimethoprim-sulfamethoxazole and short courses of parenteral ticarcillin, tobramycin, and miconazole. Altogether, 58 (65%) of 89 strains of aerobic bacteria and 28 (60%) of 47 strains of anaerobic bacteria present before prophylaxis were no longer cultured from stool specimens during prophylaxis. Ten strains of bacteria and four fungi were acquired in the stools during prophylaxis. Most fungi persisted in the throat and stools during prophylaxis. Bacterial infections occurred infrequently, but three patients developed Candida esophagitis. The regimen was well tolerated with minimal side effects.
PMCID: PMC181897  PMID: 6285808
6.  Effects of cyclophosphamide and ceftriaxone on gastrointestinal colonization of mice by Candida albicans. 
Adult male Crl:CD1 (ICR) mice were fed chow containing Candida albicans to induce sustained gastrointestinal colonization by the yeast. Groups of mice were rendered neutropenic with cyclophosphamide and subsequently received ceftriaxone, while other groups received normal saline and served as controls. Stool cultures were obtained immediately before and at the end of treatment. The administration of cyclophosphamide substantially increased the C. albicans counts in the stools of mice. The addition of ceftriaxone to the cyclophosphamide regimen did not significantly increase the level of gastrointestinal colonization by C. albicans. There was no evidence of Candida dissemination to internal organs.
PMCID: PMC163505  PMID: 8878613
7.  Antibiotics and prevention of microbial colonization of catheters. 
Antimicrobial Agents and Chemotherapy  1995;39(11):2397-2400.
Slime-producing staphylococci frequently colonize catheters, and when they are embedded in biofilm, they become resistant to various antibiotics. In the study that is described, the comparative efficacies of vancomycin, clindamycin, novobiocin, and minocycline, alone or in combination with rifampin, were tested in an in vitro model of colonization. The model consisted of the modified Robbins device with antibiotic-impregnated cement filling the lumen of catheter segments. The synergistic combination of minocycline and rifampin was the most efficacious in preventing bacterial colonization of slime-producing strains of Staphylococcus epidermidis and Staphylococcus aureus to catheter surfaces. A similar trend was observed when the inhibitory activities of polyurethane catheters coated with minocycline and rifampin were compared with the inhibitory activities of catheters coated with other antimicrobial agents. The inhibitory activities of catheters coated with minocycline and rifampin against S. epidermidis, S. aureus, and Enterococcus faecalis strains, for example, were significantly better than those of catheters coated with vancomycin (P < 0.05). The inhibitory activities of catheters coated with minocycline and rifampin against gram-negative bacilli and Candida albicans were comparable to those of catheters coated with ceftazidime and amphotericin B, respectively. We found that the combination of minocycline and rifampin is unique and highly effective in preventing the colonization of catheters with slime-producing staphylococci and that it also displays a broad-spectrum inhibitory activity against gram-negative bacteria and yeast cells.
PMCID: PMC162954  PMID: 8585715
8.  Comparative efficacies of cilofungin (Ly121019) and amphotericin B against disseminated Candida albicans infection in normal and granulocytopenic mice. 
The efficacies of cilofungin (Ly121019), a semisynthetic lipopeptide antifungal agent, and amphotericin B in the treatment of disseminated candidiasis in normal and neutropenic mice were compared. In mice infected with 2 x 10(6) CFU of Candida albicans, treatment with cilofungin in twice-daily doses of 25 or 35 mg/kg of body weight by intraperitoneal injection for 10 days gave survival rates of 83 and 90%. In contrast, there was 97% mortality in infected controls receiving 2 x 10(6) CFU intravenously and 93% survival in mice treated with 1 mg of amphotericin B per kg once a day. Mice rendered granulocytopenic by the administration of cyclophosphamide showed survival rates of 83 and 80% when treated with 25 or 35 mg of cilofungin per kg for 10 days compared with 43% survival rate in mice treated with 1 mg of amphotericin B per kg (P = 0.0030 and P = 0.0080, respectively). Similar results were obtained when the two antifungal agents were administered for a period of 30 days. Administration of 25 or 35 mg of cilofungin per kg twice a day to granulocytopenic mice receiving 10(6) CFU of C. albicans gave survival rates of 93% and 93% compared with 53% survival with amphotericin B. With 15 mg of cilofungin per kg twice a day for 10 days, a survival rate of 43 to 50% was observed in both normal and granulocytopenic mice compared with 56 and 60%, respectively, when this dosage was continued for 30 days. Cilofungin eradicated C. albicans from the kidneys, spleens, and livers of surviving animals. No toxic effects were observed with any of the dosage regimens used. The clearance of C. albicans from the kidneys, spleens, livers, and brains in normal mice was studied following infection with 5 x 10(5) and 1 x 10(5) intravenously. The mice in the treatment groups received 25 mg of cilofungin per kg twice a day for 10 days. In 8 to 12 days, this treatment was able to clear the organisms from the kidneys, spleens, and livers of mice infected with 5 x 10(5) C. albicans. Mice infected with 10(5) C. albicans and treated with cilofungin (25 mg/kg) twice a day for 10 days had no organisms in the kidney, spleen, and liver at days 8, 2, and 8, respectively. There was 1-log-unit reduction in C. albicans counts in brain tissue from mice of one of the treated groups between 2 h and 2 days postinfection, after which the numbers of organisms remained the same until day 12. These data demonstrate the efficacy of cilofungin in the treatment of disseminated C. albicans infections in normal and granulocytopenic mice. The treatment regimen used in this study was able to clear C. albicans from the kidneys, spleen, and liver but not from brain tissue.
PMCID: PMC187744  PMID: 8494367
9.  Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans. 
This study evaluated the effects of broad-spectrum antibiotics on the gastrointestinal (G.I.) yeast flora of humans and correlated the findings with those obtained from a mouse model of G.I. colonization by Candida albicans. We prospectively studied 46 adult cancer patients who received one of five broad-spectrum antibiotics (ceftriaxone, ceftazidime, ticarcillin-clavulanic acid, imipenem-cilastatin, and aztreonam) as therapy for infections. Quantitative examination of yeast colonization of stools was conducted at the baseline, at the end of antibiotic treatment, and 1 week after discontinuation of therapy. Antibiotics with anaerobic activity (ticarcillin-clavulanic acid) or high G.I. concentrations (ceftriaxone) caused a higher and more sustained increase in G.I. colonization by yeasts than did antibiotics with poor anaerobic activity (ceftazidime and aztreonam) or a low G.I. concentration (imipenem-cilastatin). These results were similar to those obtained with a mouse model of G.I. colonization by C. albicans that involved the same antibiotics. Hence, the mouse model may be useful for evaluation of yeast colonization of the human G.I. tract.
PMCID: PMC187603  PMID: 8431017
10.  In vitro activity of Ro 23-9424, a dual-action antibacterial agent, against bacterial isolates from cancer patients compared with those of other agents. 
The in vitro activity of Ro 23-9424 against bacterial isolates from patients with cancer was compared with those of fleroxacin, ciprofloxacin, cefoperazone, and ceftazidime. Ro 23-9424 inhibited the majority of the members of the family Enterobacteriaceae and all Aeromonas isolates at a concentration of less than or equal to 1.0 micrograms/ml. It was also active against Acinetobacter spp. and Haemophilus influenzae, including beta-lactamase-producing strains. The MIC for 90% of isolates (MIC90) of Pseudomonas aeruginosa was 16.0 micrograms/ml. All group A and B streptococci were inhibited by less than or equal to 0.25 micrograms/ml, and 90% of group G streptococci and Streptococcus pneumoniae were inhibited by 1.0 micrograms/ml. All methicillin-susceptible strains of Staphylococcus aureus and 60% of methicillin-resistant strains were susceptible to 2.0 micrograms of Ro 23-9424 per ml, whereas the MIC90 for Staphylococcus epidermidis and Staphylococcus hominis isolates was 4.0 micrograms/ml. Staphylococcus haemolyticus and Enterococcus spp. were less susceptible; MIC90s for them were 16.0 and 32.0 micrograms/ml. Ro 23-9424 has a broad antibacterial spectrum and potential utility for therapy of infections in cancer patients.
PMCID: PMC189479  PMID: 1503453
11.  Fluconazole susceptibility testing of Candida albicans: microtiter method that is independent of inoculum size, temperature, and time of reading. 
In vitro antifungal susceptibility testing generally remains unstandardized and unreliable for directing therapy. When azoles are tested, this problem is further compounded by the lack of definite reading end points. We determined the in vitro susceptibility of 50 Candida albicans isolates (including 10 reference strains) to fluconazole by using a microbroth dilution method in which microtiter plates were agitated immediately before reading. Six fungal inoculum sizes (ranging from 2 x 10(2) to 4 x 10(5) CFU/ml), three different times of reading (24, 48, and 72 h), and two temperatures (30 and 35 degrees C) were tested. We also compared visual and spectrophotometric determinations of MIC end points. This agitation method resulted in clear-cut visual end points that were reproducible for different observers within the same laboratory, that were independent of inoculum size, temperature of incubation, and time of reading, and that correlated well with the degree of fungal inhibition as determined by spectrophotometry. Median MICs also correlated with usually achievable levels of fluconazole in serum and tissue of humans and experimental animals.
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PMCID: PMC245233  PMID: 1823784
12.  In vitro activity of sparfloxacin (CI-978; AT-4140) against clinical isolates from cancer patients. 
Antimicrobial Agents and Chemotherapy  1990;34(11):2263-2266.
The in vitro activity of sparfloxacin, a new quinolone, was compared with those of ciprofloxacin and fleroxacin against gram-positive and gram-negative bacteria, greater than 90% of which were isolated from blood culture specimens of cancer patients. Sparfloxacin was extremely active against Acinetobacter species, Aeromonas hydrophila, Citrobacter diversus, Enterobacter species, Escherichia coli, Klebsiella species, Proteus vulgaris, and Serratia marcescens (inhibiting greater than 90% of these isolates at a concentration of 0.5 microgram/ml) and moderately active against Pseudomonas species, other Proteus species, and Citrobacter freundii. Sparfloxacin inhibited greater than 90% of staphylococci (including methicillin-resistant and coagulase-negative strains) at a concentration of 0.12 microgram/ml and greater than 90% of streptococci (including Streptococcus pneumoniae) at a concentration of 1.0 microgram/ml. It was also active against Bacillus cereus, Enterococcus species, and Corynebacterium jeikeium, organisms that have become fairly common in cancer patients.
PMCID: PMC172035  PMID: 2127348
13.  Antifungal susceptibility of 44 clinical isolates of Fusarium species determined by using a broth microdilution method. 
The MICs and minimum fungicidal concentrations of amphotericin B, natamycin, miconazole, itraconazole, and flucytosine against 17 isolates of Fusarium solani, 14 isolates of Fusarium moniliforme, 10 isolates of Fusarium oxysporum, and 3 isolates of Fusarium semitectum were determined by a broth microdilution method. Amphotericin B and natamycin were the most active agents tested and failed to show any inoculum size effect. In contrast, miconazole and itraconazole showed poor inhibitory and fungicidal activities, and the inoculum size had a major effect on the results. Flucytosine had no activity against any of the isolates tested.
PMCID: PMC172725  PMID: 2817867
14.  Resistance to ticarcillin-potassium clavulanate among clinical isolates of the family Enterobacteriaceae: role of PSE-1 beta-lactamase and high levels of TEM-1 and SHV-1 and problems with false susceptibility in disk diffusion tests. 
Thirty-four clinical isolates of the family Enterobacteriaceae from the University of Texas M. D. Anderson Cancer Center appeared resistant to ticarcillin-potassium clavulanate in agar dilution and broth macrodilution tests. Among those isolates producing a single non-class I beta-lactamase, resistance was due to production of high levels of TEM-1, SHV-1, or class IV enzymes. In five Escherichia coli isolates, production of low levels of PSE-1 was responsible for resistance which seemed due to rapid hydrolysis of ticarcillin rather than diminished susceptibility of PSE-1 to inhibition by potassium clavulanate. Comparisons of dilution and disk diffusion tests revealed major discrepancies, with 65% false susceptibility in the disk test. Revision of the interpretive criteria used for disk diffusion tests from less than or equal to 11 to less than or equal to 18 mm for resistance is proposed to resolve these discrepancies until clinical data are obtained which can be used to determine which in vitro test is most predictive of therapeutic outcome. These new criteria would diminish false susceptibility without introducing false resistance.
PMCID: PMC175869  PMID: 3143303
15.  In vitro susceptibility of Citrobacter species to various antimicrobial agents. 
The in vitro activities of 16 antimicrobial agents against 14 clinical isolates of Citrobacter diversus and 27 isolates of Citrobacter freundii were studied. C. freundii isolates were more resistant, being susceptible only to amikacin, netilmicin, gentamicin, imipenem, ciprofloxacin, and enoxacin. C. diversus isolates were susceptible to many more of the agents tested.
PMCID: PMC174846  PMID: 3606084
16.  In vitro activity of paldimycin (U-70138F) against gram-positive bacteria isolated from patients with cancer. 
The in vitro activity of paldimycin, a novel antimicrobial agent, was compared with that of vancomycin against 306 gram-positive isolates (representing 12 bacterial species) obtained from patients with cancer. Paldimycin had lower MICs for 90% of isolates than vancomycin did against most isolates tested. Its activity, however, was medium and pH dependent, being greatest in Nutrient broth at a pH of 6.8.
PMCID: PMC174800  PMID: 3606069
17.  In vitro evaluation of S-25930 and S-25932, two new quinolones, against aerobic gram-negative isolates from cancer patients. 
The in vitro activity of S-25930 and S-25932, two new 4-quinolones, against 450 aerobic gram-negative organisms isolated from cancer patients was evaluated and compared with the activity of ciprofloxacin, enoxacin, difloxacin (A-56619), and A-56620. Both agents inhibited most members of the family Enterobacteriaceae at concentrations of less than or equal to 2.0 micrograms/ml, but their activity against Pseudomonas aeruginosa was inferior to that of other quinolones. Although considerably less active than ciprofloxacin and A-56620, S-25930 was frequently two- to eightfold more active than S-25932 and was comparable to difloxacin and enoxacin against most isolates.
PMCID: PMC174661  PMID: 3471177
18.  Amphotericin B or ketoconazole therapy of fungal infections in neutropenic cancer patients. 
Fungal infections in neutropenic cancer patients have increased in frequency and constitute an important cause of morbidity and mortality. Empiric antifungal therapy is often administered to those patients who have failed to respond to antibacterial antibiotics. We conducted a prospective, randomized trial of amphotericin B and ketoconazole for 172 neutropenic cancer patients with presumed or proven fungal infections. Overall, amphotericin B and ketoconazole were equally effective. Amphotericin B may have been more effective than ketoconazole for the treatment of pneumonia. Also, five of eight Candida tropicalis infections treated with amphotericin B responded, whereas all eight infections treated with ketoconazole failed to respond (P = 0.03). Response rates for localized fungal infections were similar with both drugs. Ketoconazole should not be used as empiric antifungal therapy at institutions where there is a high frequency of infections caused by Aspergillus spp. or C. tropicalis because this agent lacks activity in vitro against these species.
PMCID: PMC174642  PMID: 3566234
19.  In vitro susceptibility of Acinetobacter species to various antimicrobial agents. 
The in vitro activity of 18 antimicrobial agents against 40 clinical isolates each of Acinetobacter calcoaceticus subsp. anitratum and Acinetobacter lwoffi was studied. Most of the newer 4-quinolone derivatives were extremely active against these organisms. Newer beta-lactam agents, such as cefpirome, BMY 28142, and BRL 36650, were also extremely active, inhibiting all strains at clinically achievable levels. Most agents were two- to fourfold more active against A. lwoffi.
PMCID: PMC176529  PMID: 3800353
20.  Imipenem-cilastatin as initial therapy for febrile cancer patients. 
Imipenem-cilastatin was used to treat 79 febrile episodes in 71 cancer patients, most of whom had neutropenia. The overall response rate was 67%, and 76% of the 45 documented infections responded. The response rates for septicemias and pneumonias were 79 and 62%, respectively. Only 1 of the 17 infections caused by gram-negative bacilli failed to respond to this therapy. The most common side effects were skin rash, nausea, and diarrhea. Eight superinfections were detected during therapy.
PMCID: PMC180520  PMID: 3532942
21.  In vitro studies of BMY-28142, a new broad-spectrum cephalosporin. 
BMY-28142 was compared with other broad-spectrum antibiotics against gram-positive cocci and gram-negative bacilli. BMY-28142 was highly active against all gram-negative bacilli and especially against Enterobacter cloacae, Serratia marcescens, and Morganella morganii. Its in vitro activity suggests that BMY-28142 should prove to be useful for the treatment of gram-negative bacillary infections.
PMCID: PMC176251  PMID: 3838637
22.  Effect of aztreonam on throat and stool flora of cancer patients. 
Eighteen patients with hematological malignancies received aztreonam in one of two dosing regimens, 1 or 2 g every 8 h for a total of 7 to 9 days. Throat and stool cultures were obtained before and during treatment with aztreonam. Aztreonam had little effect on the predominant throat flora. In contrast, facultatively anaerobic gram-negative bacilli were markedly decreased in stools during the administration of aztreonam. Strict anaerobes in the stool were variably affected by aztreonam.
PMCID: PMC180058  PMID: 6543108
23.  Clinical pharmacokinetics of aztreonam in cancer patients. 
The pharmacokinetics of aztreonam were studied in 25 adult patients with hematological malignancies. Two groups of nine patients each received aztreonam (1 or 2 g every 8 h) prophylactically, and seven infected patients received a therapeutic regimen of aztreonam (1.5 g every 4 h). The mean peak serum concentration after a 1-g dose of aztreonam (given over 0.5 h on day 1) was 75.5 micrograms/ml; after a 2-g dose it was 177.2 micrograms/ml. The mean peak serum concentration after a 1.5-g dose of aztreonam (given over 2 h on day 1) was 68.5 micrograms/ml. The serum half-life ranged between 1.7 and 2.0 h for all regimens studied. The urinary concentration of the metabolite of aztreonam, SQ 26,992, increased during 1 week of administration of the drug; however, serum levels of the metabolite were barely detectable.
PMCID: PMC179944  PMID: 6542763
24.  In vitro activities of new beta-lactam antibiotics against Acinetobacter spp. 
The in vitro activities of new beta-lactam antibiotics was studied and compared with those of other known agents against 51 clinical isolates of Acinetobacter calcoaceticus subsp. anitratus and 23 isolates of A. calcoaceticus subsp. lwoffi. Of the new beta-lactam antibiotics, imipemide (N-formimidoyl thienamycin), ceftazidime, ceftizoxime, ceftriaxone, and piperacillin demonstrated good activities. The minimal inhibitory concentrations for A. calcoaceticus subsp. lwoffi were lower than those obtained for A. calcoaceticus subsp. anitratus.
PMCID: PMC185157  PMID: 6638992
25.  Comparative in vitro activities of teichomycin and other antibiotics against JK diphtheroids. 
The in vitro susceptibilities of 98 isolates of JK diphtheroids to teichomycin, vancomycin, and eight other antibiotics was investigated. Teichomycin and vancomycin were extremely active against all the isolates tested. The 90% minimal inhibitory concentrations for teichomycin and vancomycin were 1.56 and 0.78 micrograms/ml, respectively. The majority of the isolates were resistant to ticarcillin, methicillin, erythromycin, tetracycline, chloramphenicol, clindamycin, and cephalothin.
PMCID: PMC185127  PMID: 6227280

Results 1-25 (49)