bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Resistance in
Haemophilus influenzae
and
Moraxella catarrhalis
Respiratory Tract Isolates: Results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002
Authors: Zhanel George G. , Palatnick Lorraine , Nichol Kimberly A. , Low Don E. ,   The CROSS Study Group, Hoban Daryl J.
Published: May 2003

A total of 7,566 unique patient isolates of
Haemophilus influenzae
and 2,314 unique patient isolates of
Moraxella catarrhalis
were collected between October 1997 and June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among the 7,566
H. influenzae
isolates, 22.5% produced β-lactamase, while 92.4% of the 2,314
M. catarrhalis
isolates produced β-lactamase. The incidence of β-lactamase-producing
H. influenzae
isolates decreased significantly over the 5-year study period, from 24.2% in 1997-1998 to 18.6% in 2001-2002 (
P
< 0.01). The incidence of β-lactamase-producing
M. catarrhalis
isolates did not change over the study period. The overall rates of resistance to amoxicillin and amoxicillin-clavulanate for
H. influenzae
were 19.3 and 0.1%, respectively. The rank order of cephalosporin activity based on the MICs at which 90% of isolates were inhibited (MIC
90
s) was cefotaxime > cefixime > cefuroxime > cefprozil > cefaclor. On the basis of the MICs, azithromycin was more active than clarithromycin (14-OH clarithromycin was not tested); however, on the basis of the NCCLS breakpoints, resistance rates were 2.1 and 1.6%, respectively. Rates of resistance to other agents were as follows: doxycycline, 1.5%; trimethoprim-sulfamethoxazole, 14.2%; and chloramphenicol, 0.2%. All fluoroquinolones tested, including the investigational fluoroquinolones BMS284756 (garenoxacin) and ABT-492, displayed potent activities against
H. influenzae
, with MIC
90
s of ≤0.03 μg/ml. The MIC
90
s of the investigational ketolides telithromycin and ABT-773 were 2 and 4 μg/ml, respectively, and the MIC
90
of the investigational glycylcycline GAR-936 (tigecycline) was 4 μg/ml. Among the
M. catarrhalis
isolates tested, the resistance rates derived by using the NCCLS breakpoint criteria for
H. influenzae
were <1% for all antibiotics tested except trimethoprim-sulfamethoxazole (1.5%). In summary, the incidence of β-lactamase-positive
H. influenzae
strains in Canada is decreasing (18.6% in 2001-2002), while the incidence of β-lactamase-positive
M. catarrhalis
strains has remained constant (90.0% in 2001-2002).
Treatment with a Broad-Spectrum Cephalosporin versus Piperacillin-Tazobactam and the Risk for Isolation of Broad-Spectrum Cephalosporin-Resistant
Enterobacter
Species
Authors: Schwaber Mitchell J. , Graham Camilla S. , Sands Bruce E. , Gold Howard S. , Carmeli Yehuda
Published: May 2003

Receipt of a broad-spectrum cephalosporin is a strong risk factor for isolation of broad-spectrum cephalosporin-resistant
Enterobacter
species, and yet the risk from other broad-spectrum β-lactams hydrolyzed by group 1 β-lactamases has not been well characterized. We compared the risk conferred by broad-spectrum cephalosporins to that conferred by piperacillin-tazobactam, alone or in combination with an aminoglycoside or a fluoroquinolone. A retrospective cohort was monitored from treatment onset until a broad-spectrum cephalosporin-resistant
Enterobacter
strain was isolated or the patient was discharged. There were 447 patients in the piperacillin-tazobactam group and 2,341 patients in the broad-spectrum cephalosporin group. Groups were similar in age (mean, 62.5 years). The piperacillin-tazobactam group had a smaller percentage of men (32% versus 44%,
P
< 0.001) and a lower rate of intensive care unit stay (25% versus 38%,
P
< 0.001) but a higher rate of surgery (41% versus 26%,
P
< 0.001). Groups differed in the distribution of comorbidities. Resistant
Enterobacter
strains were isolated from 62 patients, 2% in each group (hazard ratio [RR] = 1.02 [
P
= 0.95]). In multivariable analysis, risk was similar among treatment groups (RR = 0.71 [
P
= 0.32]). Intensive care unit stay and surgery were associated with increased risk (RR = 4.53 [
P
< 0.001] and RR = 1.97 [
P
= 0.015], respectively), fluoroquinolones were protective (RR = 0.24 [
P
= 0.003]), and aminoglycosides did not affect risk (RR = 0.98 [
P
= 0.95]). The protective effect of fluoroquinolones against isolation of broad-spectrum cephalosporin-resistant
Enterobacter
spp. and the equivalence in risk associated with piperacillin-tazobactam and broad-spectrum cephalosporins may have important clinical and epidemiologic implications.
Genetic and Phenotypic Variations of a ResistantPseudomonas aeruginosaEpidemic Clone
Authors: Hocquet Didier , Bertrand Xavier , Köhler Thilo , Talon Daniel , Plésiat Patrick
Published: May 2003

From May 1997 to December 2001, a serotype O:6 multidrug-resistant strain ofPseudomonas aeruginosacolonized or infected 201 patients in the University Hospital of Besançon (France). The susceptibility profile of this epidemic clone to fluoroquinolones and aminoglycosides was relatively stable during the outbreak but showed important isolate-to-isolate variations (up to 64-fold) in the MICs of β-lactams. Analysis of 18 genotypically related isolates selected on a quaterly basis demonstrated alterations in the two DNA topoisomerases II and IV (Thr83→Ile in GyrA and Ser87→Leu in ParC) and production of an ANT(2")-I enzyme. Although constitutively overproduced in these bacteria, the MexXY efflux system did not appear to contribute significantly to aminoglycoside resistance. β-Lactam resistance was associated with derepression of intrinsic AmpC β-lactamase (with isolate-to-isolate variations of up to 58-fold) and sporadic deficiency in a 46-kDa protein identified as the carbapenem-selective porin OprD. Of the 18 isolates, 14 were also found to overproduce the efflux system MexAB-OprM as a result of alteration of the repressor protein MexR (His107→Pro). However, complementation experiments with the clonedmexRgene demonstrated that MexAB-OprM contributed only marginally to β-lactam and fluoroquinolone resistance. Of the four isolates exhibiting wild-type MexAB-OprM expression despite the MexR alteration, two appeared to harbor secondary mutations in themexA-mexRintergenic region and one harbored secondary mutations in the putative ribosome binding site located upstream of themexAB oprMoperon. In conclusion, this study shows that many mechanisms were involved in the multiresistance phenotype of this highly epidemic strain ofP. aeruginosa. Our results also demonstrate that the clone sporadically underwent substantial genetic and phenotypic variations during the course of the outbreak, perhaps in relation to local or individual selective drug pressures.
Antileishmanial Activity of a Linalool-Rich Essential Oil fromCroton cajucara
Authors: Rosa Maria do Socorro S. , Mendonça-Filho Ricardo R. , Bizzo Humberto R. , Rodrigues Igor de Almeida , Soares Rosangela Maria A. , Souto-Padrón Thais , Alviano Celuta Sales , Lopes Angela Hampshire C. S.
Published: May 2003

The in vitro leishmanicidal effects of a linalool-rich essential oil from the leaves ofCroton cajucaraagainstLeishmania amazonensiswere investigated. Morphological changes inL. amazonensispromastigotes treated with 15 ng of essential oil per ml were observed by transmission electron microscopy; leishmanial nuclear and kinetoplast chromatin destruction, followed by cell lysis, was observed within 1 h. Pretreatment of mouse peritoneal macrophages with 15 ng of essential oil per ml reduced by 50% the interaction between these macrophages andL. amazonensis, with a concomitant increase by 220% in the level of nitric oxide production by the infected macrophages. Treatment of preinfected macrophages with 15 ng of essential oil per ml reduced by 50% the interaction between these cells and the parasites, which led to a 60% increase in the amount of nitric oxide produced by the preinfected macrophages. These results provide new perspectives on the development of drugs with activities againstLeishmania, as linalool-rich essential oil is a strikingly potent leishmanicidal plant extract (50% lethal doses, 8.3 ng/ml for promastigotes and 8.7 ng/ml for amastigotes) which inhibited the growth ofL. amazonensispromastigotes at very low concentrations (MIC, 85.0 pg/ml) and which presented no cytotoxic effects against mammalian cells.
In Vitro Activities of Linezolid Combined with Other Antimicrobial Agents against Staphylococci, Enterococci, Pneumococci, and Selected Gram-Negative Organisms
Authors: Sweeney Michael T. , Zurenko Gary E.
Published: May 2003

The activities of linezolid, an oxazolidinone antibacterial agent active against gram-positive organisms, alone and in combination with 35 antimicrobial agents were tested in vitro against methicillin-sensitive (n= 1 to 2 strains) and methicillin-resistant (n= 8 to 10)Staphylococcus aureusstrains; vancomycin-sensitive (n= 6) and vancomycin-resistant (n= 6 to 8)Enterococcus faecalisstrains; vancomycin-sensitive (n= 5) and vancomycin-resistant (n= 6)Enterococcus faeciumstrains; penicillin-sensitive (n= 2 to 5), penicillin-intermediate (n= 5 to 6), and penicillin-resistant (n= 5 to 6)Streptococcus pneumoniaestrains;Escherichia coli(n= 6); andKlebsiella pneumoniae(n= 6). The fractional inhibitory concentration indices of linezolid in combination with other antimicrobial agents for the organisms tested were generated on checkerboard broth microdilution plates prepared by a semiautomated method. Of 1,380 organism-drug combinations, 1,369 (99.2%) combinations of linezolid with 28 antimicrobial drugs were indifferent, 9 combinations (0.65%) of linezolid with 6 drugs (amoxicillin, erythromycin, imipenem, sparfloxacin, teicoplanin, and tetracycline) were synergistic, and 2 combinations (0.15%) of linezolid with 2 drugs (ofloxacin and sparfloxacin) were antagonistic. Overall, the in vitro data demonstrated that linezolid combined with other antimicrobial agents primarily produces an indifferent response, with infrequent occurrences of synergism and antagonism.
Experimental Study of LY333328 (Oritavancin), Alone and in Combination, in Therapy of Cephalosporin-Resistant Pneumococcal Meningitis
Authors: Cabellos Carmen , Fernàndez Antonio , Maiques Jose M. , Tubau Fe , Ardanuy Carmen , Viladrich Pedro F. , Liñares Josefina , Gudiol Francesc
Published: May 2003

Using a rabbit model of meningitis, we sought to determine the efficacy of LY333328, a semisynthetic glycopeptide, in the treatment of cephalosporin-resistant pneumococcal meningitis. LY333328 was administered at a dose of 10 mg/kg of body weight/day, alone and in combination with ceftriaxone at 100 mg/kg/day with or without dexamethasone at 0.25 mg/kg/day. The therapeutic groups were treated with LY333328 with or without dexamethasone and LY333328-ceftriaxone with or without dexamethasone. Rabbits were inoculated with a cephalosporin-resistant pneumococcal strain (ceftriaxone MIC, 2 μg/ml; penicillin MIC, 4 μg/ml; LY333328 MIC, 0.008 μg/ml) and were treated over a 26-h period beginning 18 h after inoculation. The bacterial counts in cerebrospinal fluid (CSF), the white blood cell count, the lactic acid concentration, the CSF LY333328 concentration, and bactericidal and bacteriostatic activities were determined at different time points. In vitro, LY333328 was highly bactericidal and its use in combination with ceftriaxone at one-half the MIC was synergistic. In the rabbit model, LY333328 alone was an excellent treatment for cephalosporin-resistant pneumococcal meningitis, with a rapid decrease in colony counts and no therapeutic failures. The use of LY333328 in combination with ceftriaxone improved the activity of LY333328, but no synergistic effect was observed. The combination of LY333328 with dexamethasone was also rapidly bactericidal, but two therapeutic failures were observed. The combination of LY333328 with ceftriaxone and dexamethasone was effective, without therapeutic failures.
Ribavirin and Alpha Interferon Enhance Death Receptor-Mediated Apoptosis and Caspase Activation in Human Hepatoma Cells
Authors: Schlosser Stephan F. , Schuler Markus , Berg Christoph P. , Lauber Kirsten , Schulze-Osthoff Klaus , Schmahl Friedrich Wilhelm , Wesselborg Sebastian
Published: May 2003

The molecular mechanisms underlying the clinical effects of alpha interferon (IFN) and ribavirin are not understood. Elimination of infected cells occurs in part by cytotoxic T lymphocytes (CTLs) expressing CD95 ligand and thereby attacking target cells which are positive for the death receptor CD95. Since many viruses have evolved mechanisms to inhibit apoptosis, the opposite, namely, promotion of apoptosis, could be a strategy to strengthen the host antiviral response. In the present study, we have asked whether the antiviral substances IFN and ribavirin could support CD95-mediated apoptosis by interfering with the activation of caspases, a family of proteases known for their essential role in apoptosis. HepG2 cells, stimulated with the agonistic anti-CD95 antibody, served as a minimal model to mimic the CD95 stimulation ocurring during a CTL attack of target cells in vivo. Apoptosis was quantitated by flow cytometric detection of hypodiploid nuclei. Caspase activity was measured by cytofluorometry, immunocytochemistry, and immunoblot analysis. IFN and ribavirin sensitized HepG2 cells for CD95-mediated apoptosis. This effect was correlated with an increase in CD95-mediated caspase activation and enhanced cleavage of the caspase substrate poly(ADP-ribose) polymerase. Furthermore, the positive effect on CD95-mediated caspase activation by IFN and ribavirin was confirmed by immunocytochemistry for activated caspase-3 and by immunoblot detection of activated caspase-3, caspase-7, and caspase-8. Our data demonstrate that the antiviral substances IFN and ribavirin are able to sensitize for CD95-mediated apoptosis. IFN and ribavirin also enhance CD95-mediated caspase activation, which might in part be responsible for the apoptosis-promoting effect of these antiviral compounds.
Antiviral Activity and Pharmacokinetics of 1-(2,3-Dideoxy-2-Fluoro-β-
l
-Glyceropent-2-Enofuranosyl)Cytosine
Authors: Chen Huachun , Pai S. Balakrishna , Hurwitz Selwyn J. , Chu Chung K. , Glazkova Yuliya , McClure Harold M. , Feitelson Mark , Schinazi Raymond F.
Published: May 2003

1-(2,3-Dideoxy-2-fluoro-β-
l
-glyceropent-2-enofuranosyl)cytosine (
l
-2′-Fd4C) is an
l
-nucleoside analogue with both anti-human immunodeficiency virus (HIV) and anti-hepatitis B virus (HBV) activity with median effective concentrations of 0.12 μM in peripheral blood mononuclear cells and 0.002 μM in HepG2-2.2.15 cells, respectively. The purpose of this study was to examine the antihepadnavirus potency and pharmacokinetics of
l
-2′-Fd4C in vivo. HBV-transgenic mice treated intraperitoneally with
l
-2′-Fd4C showed a reduction of HBV levels in their blood comparable to that produced by lamivudine. The pharmacokinetics of
l
-2′-Fd4C in rhesus monkeys was evaluated after intravenous and oral administration. The concentrations in plasma declined in a biexponential manner after intravenous administration, with a long terminal-phase half-life of 5.02 h. The steady-state volumes of distribution and systemic clearance were 1.09 liter · kg
−1
and 0.25 liter · h
−1
 · kg
−1
, respectively, with a renal clearance of 0.16 liter · h
−1
 · kg
−1
. The oral bioavailability was approximately 44%. About 53% of the compound administered intravenously and 19% of that administered orally were recovered unchanged in the urine within the 24-h urine collection period, and no other metabolite was detected. The compound penetrated the central nervous system at concentrations that exceeded the median effective antiviral concentration against HIV in cell cultures. Based upon these observations, further testing to develop this agent for treatment of HIV and HBV infections is warranted.
Indinavir, Efavirenz, and Abacavir Pharmacokinetics in Human Immunodeficiency Virus-Infected Subjects
Authors: DiCenzo Robert , Forrest Alan , Squires Kathleen E. , Hammer Scott M. , Fischl Margaret A. , Wu Hulin , Cha Raymond , Morse Gene D.
Published: May 2003

Adult AIDS Clinical Trials Group (AACTG) Protocol 886 examined the dispositions of indinavir, efavirenz, and abacavir in human immunodeficiency virus-infected subjects who received indinavir at 1,000 mg every 8 h (q8h) and efavirenz at 600 mg q24h or indinavir at 1,200 mg and efavirenz at 300 mg q12h with or without abacavir 300 at mg q12h. Thirty-six subjects participated. The median minimum concentration in plasma (
C
min
) for indinavir administered at 1,200 mg q12h was 88.1 nM (interquartile range [IR], 61.7 to 116.5 nM), whereas the median
C
min
for indinavir administered at 1,000 mg q8h was 139.3 nM (IR, 68.8 to 308.7 nM) (
P
= 0.19). Compared to the minimum
C
min
range for wild-type virus (80 to 120 ng/ml) estimated by the AACTG Adult Pharmacology Committee, the
C
min
for indinavir administered at 1,200 mg q12h (54 ng/ml) is inadequate. The apparent oral clearance (CL/F) (
P
= 0.28), apparent volume of distribution at steady state (
V
ss
/F) (
P
= 0.25), and half-life (
t
1/2
) (
P
= 0.80) of indinavir did not differ between regimens. The levels of efavirenz exposure were similar between regimens. For efavirenz administered at 600 mg q24h and 300 mg q12h, the median maximum concentrations in plasma (
C
max
s) were 8,968 nM (IR, 5,784 to 11,768 nM) and 8,317 nM (6,587 to 10,239 nM), respectively (
P
= 0.66), and the
C
min
s were 4,289 nM (IR, 2,462 to 5,904 nM) and 4,757 nM (IR, 3,088 to 6,644 nM), respectively (
P
= 0.29). Efavirenz pharmacokinetic parameters such as CL/F (
P
= 0.62),
V
ss
/F (
P
= 0.33), and
t
1/2
(
P
= 0.37) were similar regardless of the dosing regimen. The median
C
max
,
C
min
, CL/F,
V
ss
/
F
, and
t
1/2
for abacavir were 6,852 nM (IR, 5,702 to 7,532), 21.0 nM (IR, 21.0 to 87.5), 43.7 liters/h (IR, 37.9 to 55.2), 153.9 liters (IR, 79.6 to 164.4), and 2.0 h (IR, 1.8 to 2.8), respectively. In summary, when indinavir was given with efavirenz, the trough concentration of indinavir after administration of 1,200 mg q12h was inadequate. Abacavir did not influence the pharmacokinetics or exposure parameters of either indinavir or efavirenz. The levels of efavirenz exposure were similar in subjects receiving efavirenz q12h or q24h.
Generation of Stable Cell Lines Expressing Lamivudine-Resistant Hepatitis B Virus for Antiviral-Compound Screening
Authors: Walters Kathie-Anne , Tipples Graham A. , Allen Marchelle I. , Condreay Lynn D. , Addison William R. , Tyrrell Lorne
Published: May 2003

Lamivudine [β-
l
-(−)-2′,3′-dideoxy-3′-thiacytidine] is a potent inhibitor of hepadnavirus replication and is used both to treat chronic hepatitis B virus (HBV) infections and to prevent reinfection of transplanted livers. Unfortunately, lamivudine-resistant HBV variants do arise during prolonged therapy, indicating a need for additional antiviral drugs. Replication-competent HBV constructs containing the reverse transcriptase domain L180M/M204V and M204I (rtL180M/M204V and rtM204I) mutations associated with lamivudine resistance were used to produce stable cell lines that express the resistant virus. These cell lines contain stable integrations of HBV sequences and produce both intracellular and extracellular virus. HBV produced by these cell lines was shown to have a marked decrease in sensitivity to lamivudine, with 450- and 3,000-fold shifts in the 50% inhibitory concentrations for the rtM204I and rtL180M/M204V viruses, respectively, compared to that for the wild-type virus. Drug assays indicated that the lamivudine-resistant virus exhibited reduced sensitivity to penciclovir [9-(4-hydroxy-3-hydroxymethyl-but-1-yl) guanine] but was still inhibited by the nucleoside analogues CDG (carbocyclic 2′-deoxyguanosine) and abacavir {[1
S
,4
R
]-4-[2-amino-6-(cyclopropylamino)-9
H
-purin-9-yl]-2-cyclopentene-1-methanol}. Screening for antiviral compounds active against the lamivudine-resistant HBV can now be done with relative ease.
Activities of Ertapenem, a New Long-Acting Carbapenem, against Penicillin-Sensitive or -Resistant Pneumococci in Experimental Meningitis
Authors: Cottagnoud P. , Pfister M. , Cottagnoud M. , Acosta F. , Täuber M. G.
Published: May 2003

The penetration of ertapenem, a new carbapenem with a long half-life, reached 7.1 and 2.4% into inflamed and noninflamed meninges, respectively. Ertapenem had excellent antibacterial activity in the treatment of experimental meningitis due to penicillin-sensitive and -resistant pneumococci, leading to a decrease of 0.69 ± 0.17 and 0.59 ± 0.22 log
10
CFU/ml · h, respectively, in the viable cell counts in the cerebrospinal fluid. The efficacy of ertapenem was comparable to that of standard regimens (ceftriaxone monotherapy against the penicillin-sensitive strain and ceftriaxone combined with vancomycin against the penicillin-resistant strain). In vitro, ertapenem in concentrations above the MIC was highly bactericidal against both strains. Even against a penicillin- and quinolone-resistant mutant, ertapenem had similar bactericidal activity in vitro.
Efficacy of Albaconazole (UR-9825) in Treatment of DisseminatedScedosporium prolificansInfection in Rabbits
Authors: Capilla Javier , Yustes Clara , Mayayo Emili , Fernández Belkys , Ortoneda Montserrat , Javier Pastor F. , Guarro Josep
Published: May 2003

There are no effective therapeutics for treating invasiveScedosporium prolificansinfections. Doses of 15, 25, and 50 mg/kg of body weight/day for the new triazole albaconazole (ABC) were evaluated in an immunocompetent rabbit model of systemic infection with this mold. Treatments were begun 1 day after challenge and given for 10 days. ABC at any dose was more effective than amphotericin B (AMB) at 0.8 mg/kg/day at clearingS. prolificansfrom tissue (P< 0.007). The percentages of survival at 25 mg of ABC/kg/day were similar to those obtained with AMB. Rabbits showed 100% survival when they were treated with 50 mg of ABC per kg (P< 0.0001 versus control group), and only this dosage was able to reduce tissue burden significantly in the five organs studied, i.e., spleen, kidneys, liver, lungs, and brain.
Pharmacokinetic-Pharmacodynamic Modeling of the Electroencephalogram Effect of Norfloxacin in Rats
Authors: Chenel Marylore , Barbot Agnès , Dupuis Antoine , Mimoz Olivier , Paquereau Joël , Bouquet Serge , Couet William
Published: May 2003

A previously developed pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was used to investigate the epileptogenic activity of norfloxacin as a representative antibiotic with concentration-dependent antimicrobial activity. Rats received an intravenous infusion of norfloxacin at a rate of 5 mg kg of body weight
−1
min
−1
over 30 min. Blood samples were collected for drug assay, and an electroencephalogram (EEG) was recorded during infusion and postinfusion. An important delay was observed between concentrations of norfloxacin in plasma and the EEG effect. Indirect effect models failed to describe these data, which were successfully fitted by using an effect compartment model with a spline function to describe the relationship between effect and concentration at the effect site, as previously observed with imipenem. The robustness of the PK-PD model was then assessed by keeping the dose constant but increasing the duration of infusion to 120 and 240 min. Although this was accompanied by PK modifications, PD parameters did not vary significantly, and the PK-PD model still applied. In conclusion, the successful PK-PD modeling of the norfloxacin EEG effect in rats should be considered to predict and reduce the epileptogenic risk associated with this antibiotic as a representative fluoroquinolone (E. Fuseau and L. B. Sheiner, Clin. Pharmacol. Ther. 35:733-741, 1984).
High Prevalence of Antimicrobial Resistance in Rapidly Growing Mycobacteria in Taiwan
Authors: Yang Shun-Cheng , Hsueh Po-Ren , Lai Hsin-Chih , Teng Lee-Jene , Huang Li-Min , Chen Jong-Min , Wang Shu-Kuan , Shie Der-Chuen , Ho Shen-Wu , Luh Kwen-Tay
Published: May 2003

An increasing number of clinical isolations of rapidly growing mycobacteria (RGM) at the National Taiwan University Hospital were noted from 1992 to 2001. Broth microdilution MICs of 15 antimicrobial agents were determined for 200 clinical isolates of RGM, including the
Mycobacterium fortuitum
group (69 isolates),
M. chelonae
(39 isolates), and
M. abscessus
(92 isolates). Our results showed that the resistance rates of these isolates to the currently available agents were remarkably high. Amikacin was active against nearly all RGM isolates. Clarithromycin was usually active against
M. abscessus
(79% susceptibility) and the
M. fortuitum
group (65% susceptibility). The majority of
M. fortuitum
group isolates were susceptible to ciprofloxacin (62%) and imipenem (61%). The susceptibilities to other conventional anti-RGM agents of these isolates were poor but differed markedly by species. The newer fluoroquinolones (levofloxacin, moxifloxacin, and gatifloxacin) and meropenem showed better in vitro activities against the
M. fortuitum
group isolates than against the other two species of RGM. Linezolid had fairly good activity against these RGM isolates, particularly against
M. chelonae
isolates (82% susceptible). Telithromycin had poor activity against these RGM isolates (the MICs at which 50% of the isolates tested are inhibited [MIC
50
s] were 32 to 64 μg/ml, and the MIC
90
s were >64 μg/ml).
In Vitro Activities of Telithromycin and 10 Oral Agents against Aerobic and Anaerobic Pathogens Isolated from Antral Puncture Specimens from Patients with Sinusitis
Authors: Goldstein Ellie J. C. , Citron Diane M. , Merriam C. Vreni , Warren Yumi , Tyrrel Kerin L. , Fernandez Helen
Published: May 2003

A study of the comparative in vitro activity of telithromycin, a new ketolide, against 155 aerobic and 171 anaerobic antral sinus puncture isolates showed it to be active against a broad range of sinus pathogens. All pneumococci, including erythromycin-resistant strains, were susceptible to telithromycin at ≤0.5 μg/ml; all
Haemophilus influenzae
and
Eikenella corrodens
strains were inhibited by ≤4 μg of telithromycin/ml; all
Moraxella
spp. and beta-lactamase-producing
Prevotella
species strains were inhibited by ≤0.25 and 0.5 μg of telithromycin/ml, respectively. Among all anaerobes tested, 94% (160 of 171 strains) were susceptible to ≤4 μg of telithromycin/ml; however, 8 of 17 (47%)
Fusobacterium
strains, 2
Veillonella
strains, and 1
Peptostreptococcus micros
strain required >4 μg of telithromycin/ml for inhibition. Telithromycin may offer a therapeutic alternative for sinus infections, including those due to erythromycin-resistant pneumococci.
In Vitro Activities of Dalbavancin and Nine Comparator Agents against Anaerobic Gram-Positive Species and Corynebacteria
Authors: Goldstein Ellie J. C. , Citron Diane M. , Merriam C. Vreni , Warren Yumi , Tyrrell Kerin , Fernandez Helen T.
Published: May 2003

Dalbavancin is a novel semisynthetic glycopeptide with enhanced activity against gram-positive species. Its comparative in vitro activities and those of nine comparator agents, including daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin, against 290 recent gram-positive clinical isolates strains, as determined by the NCCLS agar dilution method, were studied. The MICs of dalbavancin at which 90% of various isolates tested were inhibited were as follows:
Actinomyces
spp., 0.5 μg/ml;
Clostridium clostridioforme
, 8 μg/ml;
C. difficile
, 0.25 μg/ml;
C. innocuum
, 0.25 μg/ml;
C. perfringens
, 0.125 μg/ml;
C. ramosum
, 1 μg/ml;
Eubacterium
spp., 1 μg/ml;
Lactobacillus
spp., >32 μg/ml,
Propionibacterium
spp., 0.5 μg/ml; and
Peptostreptococcus
spp., 0.25 μg/ml. Dalbavancin was 1 to 3 dilutions more active than vancomycin against most strains. Dalbavancin exhibited excellent activity against gram-positive strains tested and warrants clinical evaluation.
Chlamydia pneumoniae
Resists Antibiotics in Lymphocytes
Authors: Yamaguchi Hiroyuki , Friedman Herman , Yamamoto Mayumi , Yasuda Keigo , Yamamoto Yoshimasa
Published: May 2003

Chlamydia pneumoniae
infection of lymphocytes in blood has been well documented, and it is apparent that control of this pathogen in these cells may be critical in the development of chronic inflammatory diseases associated with infection by this bacterium. The activity of antibiotics against
C. pneumoniae
in lymphocytes was assessed in this study by utilizing an in vitro infection model with lymphoid cells. The results obtained indicated that although all of the antibiotics tested showed remarkable activity against bacterial growth in epithelial cells,
C. pneumoniae
in lymphocytes was less susceptible to antibiotics than was bacterial growth in epithelial cells, which are widely used for the evaluation of anti-
C. pneumoniae
antibiotics.
Lack of Vancomycin Tolerance in
Streptococcus pneumoniae
Strains Isolated in Barcelona, Spain, from 1999 to 2001
Authors: Ortega Mar , Marco Francesc , Soriano Alex , García Elisa , Martínez José A. , Mensa Josep
Published: May 2003

To evaluate the incidence of vancomycin tolerance among
Streptococcus pneumoniae
isolates, we performed killing curve studies with 633 isolates. The penicillin MIC was ≥0.12 mg/liter for 481 (76%) of the isolates. All strains were susceptible to vancomycin. Killing curve studies were performed with a vancomycin concentration of 2.5 mg/liter. The Tupelo strain was used for quality control. No vancomycin-tolerant strain was detected.
RNA III Inhibiting Peptide Inhibits In Vivo Biofilm Formation by Drug-Resistant
Staphylococcus aureus
Authors: Giacometti Andrea , Cirioni Oscar , Gov Yael , Ghiselli Roberto , Del Prete Maria Simona , Mocchegiani Federico , Saba Vittorio , Orlando Fiorenza , Scalise Giorgio , Balaban Naomi , Dell'Acqua Giorgio
Published: May 2003

Staphylococcus aureus
is a prevalent cause of bacterial infections associated with indwelling medical devices. RNA III inhibiting peptide (RIP) is known to inhibit
S. aureus
pathogenesis by disrupting quorum-sensing mechanisms. RIP was tested in the present study for its ability to inhibit
S. aureus
biofilm formation in a rat Dacron graft model. The activity of RIP was synergistic with those of antibiotics for the complete prevention of drug-resistant
S. aureus
infections.
Linezolid and Vancomycin, Alone and in Combination with Rifampin, Compared with Moxifloxacin against a Multidrug-Resistant and a Vancomycin-Tolerant
Streptococcus pneumoniae
Strain in an In Vitro Pharmacodynamic Model
Authors: Cha Raymond , Rybak Michael J.
Published: May 2003

Potential alternatives, including linezolid, adjunctive rifampin, and moxifloxacin, were evaluated against vancomycin-tolerant (P9802-020) and vancomycin-susceptible clinical isolates of
Streptococcus pneumoniae
in an in vitro pharmacodynamic model. Vancomycin exhibited maximal killing of 2-log
10
CFU/ml against P9802-020. Linezolid, moxifloxacin, and linezolid plus rifampin exhibited 99.9% killing against both isolates. These alternatives should be considered for further evaluation against vancomycin-tolerant
S. pneumoniae
.
Eradication of Resident Bacteria of Normal Human Skin by Antimicrobial Ointment
Authors: Hendley J. Owen , Ashe Kathleen M.
Published: May 2003

The application of a topical triple-antibiotic ointment (containing neomycin, polymyxin, and bacitracin) eradicated resident bacteria through 25 layers of the stratum corneum and prevented repopulation of bacteria overnight but not at 1 week. Through 15 layers, mupirocin had some effect, whereas a double-antibiotic ointment had none. The reservoir of resident bacteria in the sebaceous glands is not affected by a topical antibiotic.
Stability and Antibacterial Activity of Cefepime during Continuous Infusion
Authors: Sprauten Pål F. , Beringer Paul M. , Louie Stan G. , Synold Timothy W. , Gill Mark A.
Published: May 2003

The stability of cefepime during simulated continuous infusion was determined with a motorized portable infusion pump worn over a period of 24 to 36 h. Susceptibility testing on cefepime solutions over time indicates that the degradation products do not exhibit antibacterial activity. Cefepime stability at 24 h following continuous infusion was 94.3% ± 1.0%, which supports the use of continuous infusion.
Killing Activity of Micafungin against
Aspergillus fumigatus
Hyphae Assessed by Specific Fluorescent Staining for Cell Viability
Authors: Watabe Etsuko , Nakai Toru , Matsumoto Satoru , Ikeda Fumiaki , Hatano Kazuo
Published: May 2003

We studied the anti-
Aspergillus
activity of micafungin by using two fluorescent dyes to detect cell viability. Micafungin induced flattened hyphae, caused by the bursting of cells, which had lost their viability. Micafungin has killing activity against actively growing hyphae, even though it is not fungicidal against the whole burden of
Aspergillus fumigatus
.
Risk Factors for Fecal Quinolone-Resistant
Escherichia coli
in Mexican Children
Authors: Zaidi Mussaret B. , Zamora Emma , Diaz Pilar , Tollefson Linda , Fedorka-Cray Paula J. , Headrick Marcia L.
Published: May 2003

We determined the prevalence of, and risk factors for, fecal quinolone-resistant
Escherichia coli
(QREC) in 324 children from Yucatan, Mexico. QREC was higher in children with recent
Salmonella
infection (100%) than in children with diarrhea (61%) or healthy children (54%) (
P
= 0.007). Multivariate analysis identified recent hospitalization of a family member (
P
= 0.011, odds ratio [OR] = 5.1) and carriage of
Salmonella
(
P
= 0.004, OR = 3.7) as independent risk factors for QREC.
Evolution of Antibiotic Resistance in
Salmonella enterica
Serovar Typhimurium Strains Isolated in the Czech Republic between 1984 and 2002
Authors: Faldynova M. , Pravcova M. , Sisak F. , Havlickova H. , Kolackova I. , Cizek A. , Karpiskova R. , Rychlik I.
Published: May 2003

In a collection of 66
Salmonella enterica
serovar Typhimurium strains isolated between 1984 and 2002 in the Czech Republic, genes coding for antibiotic resistance were determined by using specific PCRs. We found that the pentadrug-resistant ACSSuT clone first appeared in the Czech Republic in 1990. A new variant of the
aadA
gene designated
aadA21
is described, the 5′ end of which was identical to
aadA2
and the 3′ end of which was identical to
aadA1
.
Salmonella enterica
Serovar Typhi Strains Isolated in Korea Containing a Multidrug Resistance Class 1 Integron
Authors: Pai Hyunjoo , Byeon Jeong-hum , Yu Sunmi , Lee Bok Kwon , Kim Shukho
Published: May 2003

Six strains of
Salmonella enterica
serovar Typhi which were resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, streptomycin, tetracycline, and gentamicin were isolated in Korea. This multidrug resistance was transferred by a conjugative plasmid of about 50 kb. The plasmid harbored a class 1 integron, which included six resistance genes,
aacA4b
,
catB8
,
aadA1
,
dfrA1
,
aac
(
6′
)-
IIa
, and the novel
blaP2
, in that order. All of the isolates showed the same-size plasmids and the same ribotyping patterns, which suggests a clonal spread of these multidrug-resistant isolates.
Molecular Characterization of Isoniazid-Resistant
Mycobacterium tuberculosis
Clinical Isolates in Lithuania
Authors: Bakonyte Daiva , Baranauskaite Aurelija , Cicenaite Jurate , Sosnovskaja Anaida , Stakenas Petras
Published: May 2003

Mutations at codon 315 of the
katG
gene were detected in 312 of 364 (85.7%) isoniazid-resistant
Mycobacterium tuberculosis
isolates. Seven of 52 (13.5%) isoniazid-resistant isolates with the wild-type Ser315 codon and 10 of 52 (19.2%) isoniazid-resistant isolates with a mutated
katG
allele had mutation −15C→T in the promoter of the
mabA-inhA
operon.
Comparative Roles of the Cell Wall and Cell Membrane in Limiting Uptake of Xenobiotic Molecules by
Saccharomyces cerevisiae
Authors: Aouida Mustapha , Tounekti Omar , Belhadj Omrane , Mir Lluis M.
Published: May 2003

Using reversible electropermeabilization of cells and spheroplasts, we show that the cell wall and plasma membrane partly account for bleomycin resistance by acting as two independent barriers. We also report on the presence of a membrane protein that may be responsible for bleomycin internalization and toxicity in
Saccharomyces cerevisiae
.
Vancomycin Penetration of Uninfected Pleural Fluid Exudate after Continuous or Intermittent Infusion
Authors: Byl Baudouin , Jacobs Frédérique , Wallemacq Pierre , Rossi Camelia , de Francquen Philippe , Cappello Matteo , Leal Teresinha , Thys Jean-Pierre
Published: May 2003

Blood and pleural exudate samples were obtained from 16 patients receiving intermittent or continuous infusions of vancomycin after lung surgery. The areas under the concentration-time curves for blood and pleural exudates were identical for both administration schedules, while continuous infusion allowed the concentrations in pleural exudates to be more sustained (mean concentration, 12 mg/liter).
Influence of Reduced Susceptibility to Glycopeptides on Activities of Vancomycin and Teicoplanin against
Staphylococcus aureus
in Experimental Endocarditis
Authors: Pavie Juliette , Lefort Agnès , Ploy Marie-Cécile , Massias Laurent , Chau Françoise , Garry Louis , Denis François , Fantin Bruno
Published: May 2003

The influence of reduced susceptibilities to glycopeptides on the activities of vancomycin and teicoplanin against an isogenic pair of clinical
Staphylococcus aureus
strains in experimental endocarditis was investigated. While vancomycin was similarly active against both strains, teicoplanin was approximately 100-fold less active against the resistant strain and selected for the emergence of more resistant subpopulations.
Alpha Interferon Augments Cidofovir's Antiviral and Antiproliferative Activities
Authors: Johnson Jeffrey A. , Gangemi J. David
Published: May 2003

The antiviral and antiproliferative activities of alpha 2a interferon (IFN-α2a) and cidofovir in human papillomavirus type 16 (HPV-16)-transformed keratinocytes were evaluated. The compounds in combination were more effective than comparable levels of either drug alone. Evaluation of effective drug ratios revealed a synergistic cooperation between IFN-α2a and cidofovir in inhibiting the proliferation of HPV-infected cells.
Antimicrobial Resistance of
Campylobacter jejuni
subsp.
jejuni
Strains Isolated from Humans in 1998 to 2001 in Montréal, Canada
Authors: Gaudreau Christiane , Gilbert Huguette
Published: May 2003

The rates of resistance of 51 to 72 human strains of
Campylobacter jejuni
subsp.
jejuni
isolated annually from 1998 to 2001 in Montréal, Québec, Canada, varied from 1 to 12% for erythromycin, 43 to 68% for tetracycline, and 10 to 47% for ciprofloxacin. In the last years of the study, there was a significant increase in the rate of resistance to ciprofloxacin (
P
= 0.00003) but not in the rate of resistance to erythromycin (
P
= 0.056) or tetracycline (
P
= 0.095) compared to the rate obtained in the first years. All 51
C. jejuni
strains isolated in 2001 were susceptible to gentamicin, amoxicillin-clavulanic acid, imipenem, and meropenem. From 1999 to 2001, 74 strains of
C. jejuni
acquired abroad were significantly more resistant to ciprofloxacin than 109 strains of
C. jejuni
acquired locally (66 versus 9%,
P
< 0.00001) but were not significantly more resistant to erythromycin (1 versus 6%,
P
= 0.15) or to tetracycline (55 versus 58%,
P
= 0.87).
Emergence of Resistance in Normal Human Aerobic Commensal Flora during Telithromycin and Amoxicillin-Clavulanic Acid Treatments
Authors: Crémieux Anne-Claude , Muller-Serieys Claudette , Panhard Xavière , Delatour Frédérique , Tchimichkian Marina , Mentre France , Andremont Antoine
Published: May 2003

Mean fecal global yeast counts increased similarly during 7 days of treatment with telithromycin (800 mg once daily) or amoxicillin-clavulanic acid (amoxiclav) (1 g of amoxicillin and 125 mg of clavulanic acid 3 times daily) in human volunteers and decreased slowly thereafter. On skin, coagulase-negative staphylococci of decreased susceptibility (DS) to telithromycin increased in the telithromycin group, whereas those with DS to methicillin increased in the amoxiclav group. A similar antibiotic-related shift towards homologous DS was observed for oral nongroupable streptococci (NGS), but in addition, the prevalence of NGS resistant to both classes of antibiotics was significantly greater in the amoxiclav group at days 8 (
P
< 0.01) and 45 (
P
< 0.015).
Resistance to Autolysis in Vancomycin-Selected
Staphylococcus aureus
Isolates Precedes Vancomycin-Intermediate Resistance
Authors: Boyle-Vavra Susan , Challapalli Mamatha , Daum Robert S.
Published: May 2003

Four clinical U.S. glycopeptide intermediate resistant
Staphylococcus aureus
(GISA) isolates were resistant to Triton X-100-induced autolysis. Similar resistance was demonstrated in an isolate obtained after a single passage of a susceptible clinical isolate in low-level vancomycin. Strains with the vancomycin-induced Triton X-100 resistance phenotype produced active murein hydrolases but were resistant to lysis by murein hydrolases.
Biochemical Characterization of β-Lactamases Bla1 and Bla2 from
Bacillus anthracis
Authors: Materon Isabel C. , Queenan Anne Marie , Koehler Theresa M. , Bush Karen , Palzkill Timothy
Published: May 2003

The Sterne and Ames strains of
Bacillus anthracis
carry chromosomal genes
bla1
and
bla2
, which confer β-lactam resistance when expressed in
Escherichia coli
. MIC measurements and steady-state kinetic analyses indicate that Bla1 possesses penicillinase activity while Bla2 possesses penicillinase, cephalosporinase, and carbapenem-hydrolyzing activities.
Prodrugs of Cephalosporin RWJ-333441 (MC-04,546) with Improved Aqueous Solubility
Authors: Hecker Scott J. , Calkins Trevor , Price Mary E. , Huie Keith , Chen Sharon , Glinka Tomasz W. , Dudley Michael N.
Published: May 2003

To improve the aqueous solubility of anti-methicillin-resistant
Staphylococcus aureus
cephalosporin RWJ-333441 for parenteral administration, acyl derivatives of the C-3 primary amino group were prepared and evaluated for solubility, cleavage in serum in vitro, and conversion to RWJ-333441 in vivo. Improved solubility at physiologic pH values and release of RWJ-333441 in vitro and in vivo were observed for several prodrugs, including the aspartate derivative RWJ-333442.
Mechanism of Action of 4-Phenoxyphenoxyethyl Thiocyanate (WC-9) against
Trypanosoma cruzi
, the Causative Agent of Chagas’ Disease
Authors: Urbina Julio A. , Concepcion Juan Luis , Montalvetti Andrea , Rodriguez Juan B. , Docampo Roberto
Published: May 2003

We investigated the molecular basis of the activity of 4-phenoxyphenoxyethyl thiocyanate (WC-9) against
Trypanosoma cruzi
, the etiological agent of Chagas’ disease. We found that growth inhibition of
T. cruzi
epimastigotes induced by this compound was associated with a reduction in the content of the parasite's endogenous sterols due to a specific blockade of their de novo synthesis at the level of squalene synthase.
Inhibitors of Pantothenate Kinase: Novel Antibiotics for Staphylococcal Infections
Authors: Choudhry Anthony E. , Mandichak Tracy L. , Broskey John P. , Egolf Richard W. , Kinsland Cynthia , Begley Tadhg P. , Seefeld Mark A. , Ku Thomas W. , Brown James R. , Zalacain Magdalena , Ratnam Kapila
Published: May 2003

Pantothenate kinase (CoaA) catalyzes the first step of the coenzyme A biosynthetic pathway. Here we report the identification of the
Staphylococcus aureus coaA
gene and characterization of the enzyme. We have also identified a series of low-molecular-weight compounds which are effective inhibitors of
S. aureus
CoaA.
Detection of CMY-2, CTX-M-14, and SHV-12 β-Lactamases in
Escherichia coli
Fecal-Sample Isolates from Healthy Chickens
Authors: Briñas Laura , Moreno Miguel Angel , Zarazaga Myriam , Porrero Concepción , Sáenz Yolanda , García María , Dominguez Lucas , Torres Carmen
Published: May 2003

Genes encoding the CMY-2, CTX-M-14, and SHV-12 β-lactamases were detected in three of five
Escherichia coli
isolates from fecal samples from healthy chickens which showed resistance or diminished susceptibility to extended-spectrum cephalosporins. A −42 mutation at the promoter region of the
ampC
gene was detected in the other two isolates.
Examination of Diverse Toxin-Coregulated Pilus-Positive
Vibrio cholerae
Strains Fails To Demonstrate Evidence for
Vibrio
Pathogenicity Island Phage
Authors: Faruque Shah M. , Zhu Jun , Asadulghani  , Kamruzzaman M. , Mekalanos John J.
Published: May 2003

The major virulence factors of toxigenic
Vibrio cholerae
are cholera toxin, which is encoded by a lysogenic filamentous bacteriophage (CTXΦ), and toxin-coregulated pilus (TCP), an essential colonization factor that is also the receptor for CTXΦ. The genes involved in the biosynthesis of TCP reside in a pathogenicity island, which has been reported to correspond to the genome of another filamentous phage (designated VPIΦ) and to encode functions necessary for the production of infectious VPIΦ particles. We examined 46
V. cholerae
strains having diverse origins and carrying different genetic variants of the TCP island for the production of the VPIΦ and CTXΦ in different culture conditions, including induction of prophages with mitomycin C and UV irradiation. Although 9 of 10
V. cholerae
O139 strains and 12 of 15 toxigenic El Tor strains tested produced extracellular CTXΦ, none of the 46 TCP-positive strains produced detectable VPIΦ in repeated assays, which detected as few as 10 particles of a control CTX phage per ml. These results contradict the previous report regarding VPIΦ-mediated horizontal transfer of the TCP genes and suggest that the TCP island is unable to support the production of phage particles. Further studies are necessary to understand the mechanism of horizontal transfer of the TCP island.
Mammalian Transforming Growth Factor β1 Activated after Ingestion byAnopheles stephensiModulates Mosquito Immunity
Authors: Luckhart Shirley , Crampton Andrea L. , Zamora Ruben , Lieber Matthew J. , Dos Santos Patricia C. , Peterson Tina M. L. , Emmith Nicole , Lim Junghwa , Wink David A. , Vodovotz Yoram
Published: May 2003

During the process of bloodfeeding byAnopheles stephensi, mammalian latent transforming growth factor β1 (TGF-β1) is ingested and activated rapidly in the mosquito midgut. Activation may involve heme and nitric oxide (NO), agents released in the midgut during blood digestion and catalysis ofl-arginine oxidation byA. stephensiNO synthase (AsNOS). Active TGF-β1 persists in the mosquito midgut to extended times postingestion and is recognized by mosquito cells as a cytokine. In a manner analogous to the regulation of vertebrate inducible NO synthase and malaria parasite (Plasmodium) infection in mammals by TGF-β1, TGF-β1 regulatesAsNOSexpression andPlasmodiumdevelopment inA. stephensi. Together, these observations indicate that, through conserved immunological cross talk, mammalian and mosquito immune systems interface with each other to influence the cycle ofPlasmodiumdevelopment.