Abstract:
:Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation, and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOΔmutS (MIC of ciprofloxacin [MICciprofloxacin], 0.25 mg/liter; MICmeropenem, 2 mg/liter) and CW44 (MICciprofloxacin, 0.5 mg/liter; MICmeropenem, 4 mg/liter), were investigated for 120 h. Concentration-time profiles achievable in epithelial lining fluid (ELF) following FDA-approved doses were simulated in the CBR. Treatments were ciprofloxacin at 0.4 g every 8 h as 1-h infusions (80% ELF penetration), meropenem at 6 g/day as a continuous infusion (CI) (30% and 60% ELF penetration), and their combinations. Counts of total and less-susceptible planktonic and biofilm bacteria and MICs were determined. Antibiotic concentrations were quantified by an ultrahigh-performance liquid chromatography photodiode array (UHPLC-PDA) assay. For both strains, all monotherapies failed, with substantial regrowth and resistance of planktonic (≥8 log10 CFU/ml) and biofilm (>8 log10 CFU/cm2) bacteria at 120 h (MICciprofloxacin, up to 8 mg/liter; MICmeropenem, up to 64 mg/liter). Both combination treatments demonstrated synergistic bacterial killing of planktonic and biofilm bacteria of both strains from ∼48 h onwards and suppressed regrowth to ≤4 log10 CFU/ml and ≤6 log10 CFU/cm2 at 120 h. Overall, both combination treatments suppressed the amplification of resistance of planktonic bacteria for both strains and of biofilm bacteria for CW44. The combination with meropenem at 60% ELF penetration also suppressed the amplification of resistance of biofilm bacteria for PAOΔmutS Thus, combination treatment demonstrated synergistic bacterial killing and resistance suppression against difficult-to-treat hypermutable P. aeruginosa strains.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Bilal H,Bergen PJ,Tait JR,Wallis SC,Peleg AY,Roberts JA,Oliver A,Nation RL,Landersdorfer CBdoi
10.1128/AAC.00469-20subject
Has Abstractpub_date
2020-06-23 00:00:00issue
7eissn
0066-4804issn
1098-6596pii
AAC.00469-20journal_volume
64pub_type
杂志文章abstract::Susceptibility of pathogenic aerobic bacteria to moxalactam (LY127935) was compared by two methods, diffusion from 30-microgram disks and agar plate dilution. The two methods gave a satisfactory degree of correlation when compared by linear regression, but the slope of the linear regression was significantly steeper f...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.19.1.130
更新日期:1981-01-01 00:00:00
abstract::A unique group of viridans streptococci has been found in South Africa. These organisms were isolated in close temporal and physical proximity to the isolation of penicillin-resistant pneumococci. The strains were resistant to penicillin, oxacillin, the cephalosporins (all generations), piperacillin, azlocillin, and m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.5.702
更新日期:1983-11-01 00:00:00
abstract::The present study demonstrates the in vitro effectiveness of the macrolide rokitamycin and the phenothiazine compound chlorpromazine against Acanthamoeba castellanii. Growth curve evaluations revealed that both drugs inhibit trophozoite growth in dose- and time-dependent ways. The effects of both drugs when they were ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.12.4520-4527.2004
更新日期:2004-12-01 00:00:00
abstract::Demethylchlortetracycline and, to a lesser extent, chlortetracycline were found to mediate the in vitro photoinactivation of Venezuelan equine encephalitis virus. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.10.1.176
更新日期:1976-07-01 00:00:00
abstract::Enterococcus gallinarum N04-0414 (MIC for vancomycin, 256 microg/ml) harbored a vanD-type vancomycin resistance operon as well as the intrinsic vanC1 operon. The D-Ala:D-Ala ligase 2 gene (ddl2) was not present in the strain, though it is found downstream of the vanS gene from the vanC operon in E. gallinarum ATCC 495...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.3.1067-1070.2006
更新日期:2006-03-01 00:00:00
abstract::The assembly of hepatitis B virus (HBV) core protein (HBc) into capsids represents a critical step of viral replication. HBc has multiple functions during the HBV life cycle, which makes it an attractive target for antiviral therapies. Capsid assembly modulators (CAMs) induce the formation of empty capsid or aberrant ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00835-18
更新日期:2018-09-24 00:00:00
abstract::In order to study the mechanism of insusceptibility of Spiroplasma citri to rifampin, we have cloned and sequenced its rpoB gene, which encodes the beta subunit of RNA polymerase. By comparison of the deduced amino acid sequence with sequences of beta subunits from susceptible and resistant bacteria, it was possible t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.4.858
更新日期:1996-04-01 00:00:00
abstract::High-dose clindamycin (CLDM) and benzylpenicillin (PCG) are the recommended chemotherapeutic remedies for toxic shock-like syndrome caused by group A streptococci. One reason for this is that it has been shown that CLDM suppresses the expression of some exoproteins, e.g., SpeB, SpeA, and streptolysin O (Slo). We analy...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.1.88-96.2005
更新日期:2005-01-01 00:00:00
abstract::Burkholderia pseudomallei, the causative agent of melioidosis, is inherently resistant to a variety of antibiotics including aminoglycosides, macrolides, polymyxins, and beta-lactam antibiotics. Despite resistance to many beta-lactams, ceftazidime and beta-lactamase inhibitor-beta-lactam combinations are commonly used...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.7.2082-2087.2003
更新日期:2003-07-01 00:00:00
abstract::Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02204-15
更新日期:2015-12-01 00:00:00
abstract::Fifty strains of Mycoplasma pneumoniae in L cells were tested for susceptibility to macrolide antibiotics. Rokitamycin, a new macrolide antibiotic, was most active against these organisms, with an MIC for 90% of strains of 0.007 microgram/ml. The MICs of erythromycin, josamycin, and kitasamycin for 90% of strains were...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.11.1843
更新日期:1987-11-01 00:00:00
abstract::Grazoprevir (GZR) plus elbasvir is an approved treatment for chronic infection with hepatitis C virus (HCV) genotype 1 or 4. HCV infection complications include liver cirrhosis, end-stage liver disease, and hepatocellular carcinoma. The objective of this study was to evaluate the pharmacokinetics and safety of multipl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00813-17
更新日期:2017-11-22 00:00:00
abstract::Aminoglycoside 2″-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci. We describe a novel aminoglycoside 2″-phosphotransferase from the Gram-negative pathogen Campylobacter jejuni, which shares 78% amino acid sequence identity with the APH(2″)-Ia do...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02049-12
更新日期:2013-01-01 00:00:00
abstract::The antibiotic tolerances of bacterial persisters have been attributed to transient dormancy. While persisters have been observed to be growth inhibited prior to antibiotic exposure, we sought to determine whether such a trait was essential to the phenotype. Furthermore, we sought to provide direct experimental eviden...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00243-13
更新日期:2013-07-01 00:00:00
abstract::Nonreplicating bacteria are known to be (or at least commonly thought to be) refractory to antibiotics to which they are genetically susceptible. Here, we explore the sensitivity to killing by bactericidal antibiotics of three classes of nonreplicating populations of planktonic bacteria: (i) stationary phase, when the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02360-18
更新日期:2019-06-24 00:00:00
abstract::DNA ligases are indispensable enzymes playing a critical role in DNA replication, recombination, and repair in all living organisms. Bacterial NAD+-dependent DNA ligase (LigA) was evaluated for its potential as a broad-spectrum antibacterial target. A novel class of substituted adenosine analogs was discovered by targ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01181-10
更新日期:2011-03-01 00:00:00
abstract::The Chinese traditional medicine mao-bushi-saishin-to (MBST), which has anti-inflammatory effects and has been used to treat the common cold and nasal allergy in Japan, was examined for its effects on the therapeutic activity of a new benzoxazinorifamycin, KRM-1648 (KRM), against Mycobacterium avium complex (MAC) infe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.3.514
更新日期:1999-03-01 00:00:00
abstract::Accumulating data have brought the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) into the forefront of antiretroviral therapy. Among the emerging compounds in this class, a particularly attractive one is efavirenz (Sustiva), recently approved for clinical use by the U.S. Food and Drug Administration. In...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.5.1186-1194.2000
更新日期:2000-05-01 00:00:00
abstract::Heteroresistance is the coexistence of populations with differing nucleotides at a drug resistance locus within a sample of organisms. Although Sanger sequencing is the gold standard for sequencing, it may be less sensitive than deep sequencing for detecting fluoroquinolone heteroresistance in Mycobacterium tuberculos...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02066-13
更新日期:2014-06-01 00:00:00
abstract::Nine carbapenem-resistant Enterobacteriaceae isolates collected from eight patients in five German hospitals were investigated. Six isolates produced the OXA-48 carbapenemase, and three isolates produced OXA-162, which is a point mutant form of OXA-48. Both carbapenemase genes were located on IncL/M-type conjugative p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05315-11
更新日期:2012-04-01 00:00:00
abstract::Fifty volunteers randomly assigned to one of five hand washing agents (10 subjects per agent)--a nonantiseptic liquid soap (control), an antiseptic hand rinse containing 60% isopropyl alcohol (IPA) with emollients (Alc A), an antiseptic hand rinse containing 70% IPA and 0.5% chlorhexidine gluconate with emollients (Al...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.30.4.542
更新日期:1986-10-01 00:00:00
abstract::The in vitro activity of HSR-903, an oral quinolone, against 196 recent clinical isolates of respiratory pathogens was evaluated. HSR-903 was 2 to 32 times more active than ofloxacin, ciprofloxacin, and sparfloxacin against Staphylococcus aureus, including methicillin-resistant strains, and Streptococcus pneumoniae an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.7.1767
更新日期:1999-07-01 00:00:00
abstract::Data comparing the treatment outcomes of the two most frequently recommended empirical antibiotic regimens for community-acquired pneumonia (CAP)--combination therapy with an extended-spectrum beta-lactam and a macrolide (BL+M) or fluoroquinolone (F) monotherapy--for patients with severe CAP are sparse. The purpose of...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00006-07
更新日期:2007-11-01 00:00:00
abstract::Eravacycline is a fluorocycline antibiotic in phase 3 clinical development for complicated intra-abdominal and urinary tract infections. To support its clinical development, a study was conducted to evaluate the effects of various susceptibility test parameters on the MIC values for aerobic bacteria. The results showe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04727-14
更新日期:2015-04-01 00:00:00
abstract::A wide variety of prokaryotic and eukaryotic cells exhibit a multidrug resistance (MDR) phenotype, indicating that resistance to potentially toxic compounds is mediated by their active efflux from the cell. We have sought to determine whether resistance to azoles in some strains of Candida species may be due in part t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.2.419
更新日期:1996-02-01 00:00:00
abstract::The bioactivity of imipenem at 20 micrograms/ml in various agar and broth media which are commonly used in susceptibility test assays was measured at different storage temperatures over time. Imipenem was found to be more stable at 4 degrees C than at -20 degrees C and least stable in all media at 35 degrees C. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.6.781
更新日期:1984-06-01 00:00:00
abstract::A spontaneous Escherichia coli mutant, named Q3, resistant to nalidixic acid was obtained from a previously described clinical isolate of E. coli, Q2, resistant to fluoroquinolones but susceptible to nalidixic acid (E. Cambau, F. Bordon, E. Collatz, and L. Gutmann, Antimicrob. Agents Chemother. 37:1247-1252, 1993). Q3...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.1.85
更新日期:1997-01-01 00:00:00
abstract::The susceptibility to 14 antimicrobial agents and the mechanisms of aminopenicillin resistance were studied in 197 clinical isolates of Haemophilus influenzae--109 isolated in 2007 (study group) and 88 isolated in 1997 (control group). Community antibiotic consumption trends were also examined. H. influenzae strains w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01674-07
更新日期:2008-08-01 00:00:00
abstract::The intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime were studied in 68 volunteers who received single, oral doses of azithromycin (0.5 g), clarithormycin (0.5 g), ciprofloxacin (0.5 g), or cefuroxime (0.5 g). In subgroups of four subjects each, the subjects underwent bron...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.7.1617
更新日期:1996-07-01 00:00:00
abstract::Many risk factors associated with aminoglycoside nephrotoxicity have been identified in humans and experimental animals. They include an initial high rate of creatinine clearance, high initial peak levels in serum, age, sex, duration of therapy, liver disease, and renal infection. The concomitant administration of ste...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.7.992
更新日期:1988-07-01 00:00:00