Antibiograms of Multidrug-Resistant Clinical Acinetobacter baumannii: Promising Therapeutic Options for Treatment of Infection with Colistin-Resistant Strains

Li, Jian; Nation, Roger L.; Owen, Roxanne J.; Wong, Stephanie; Spelman, Denis; Franklin, Clare

doi:10.1086/520658

Cited by 146 publications

(134 citation statements)

References 21 publications

Supporting

Mentioning

113

Contrasting

Unclassified

Order By: Relevance

“…Twenty-seven of 45 MDR A. baumannii isolates were resistance to rifampicin (MIC ranges 3-8 µg/ml); 16 isolates revealed synergy, partial synergy, and additive results for cefoperazone/sulbactam plus rifampicin, 5 isolates revealed partial synergy and additive results for imipenem plus rifampicin, 5 isolates revealed partial synergy and additive results for cefoperazone/sulbactam plus rifampicin and colistin plus rifampicin, 1 isolate revealed partial synergy and additive results for cefoperazone/sulbactam plus rifampicin, imipenem plus rifampicin and colistin plus rifampicin. Although Rifampicin is a hydrophobic antibiotic, its negative charge and large molecular size cause it to be unable to effectively penetrate through the outer membrane of A. baumannii alone 5 . Other antibiotics which combine with rifampicin may be related to substantial changes in the outer membrane of A. baumannii isolates; thus enhancing the ability of rifampicin to penetrate into the cell 29 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antimicrobial susceptibility of Acinetobacter baumannii isolated from hospital patients

Tunyapanit¹,

Pruekprasert²,

Laoprasopwattana³

et al. 2014

ScienceAsia

View full text Add to dashboard Cite

ABSTRACT:The incidence of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) is increasing worldwide and is leading to therapeutic problems. We investigated the in vitro activities of cefoperazone/sulbactam, colistin, imipenem, and rifampicin alone and in double combinations against 100 A. baumannii isolates from patients at Songklanagarind Hospital in Songkhla Province, Thailand. The E-test method was used to determine antimicrobial susceptibility, the minimal inhibitory concentration (MIC) and for antimicrobial combination testing. A. baumannii isolates were susceptible to colistin (97%), cefoperazone/sulbactam (69%), imipenem (45%), and rifampicin (13%). Fifty-nine percent of them were MDR A. baumannii. Colistin was superior to cefoperazone/sulbactam, rifampicin and imipenem against MDR A. baumannii and the MIC50, MIC90 of colistin were 0.75 and 1 µg/ml, respectively. Non-MDR A. baumannii isolates were susceptible to cefoperazone/sulbactam (100%), colistin (95%), imipenem (93%) and rifampicin (2%). Combinations of cefoperazone/sulbactam plus colistin or rifampicin, imipenem plus colistin or rifampicin and colistin plus rifampicin showed indifferent effects against most MDR isolates. Of all the antimicrobial combinations tested, cefoperazone/sulbactam plus rifampicin produced the highest percentages (42%) of synergy, partial synergy, and additive results. The activity rate of cefoperazone/sulbactam against MDR A. baumannii was higher when combined with rifampicin than colistin. Thus colistin had the greatest activity against most MDR and non-MDR A. baumannii isolates among all of the antibiotics tested. Cefoperazone/sulbactam and imipenem showed good activity against non-MDR isolates, and cefoperazone/sulbactam combined with rifampicin may be useful in treating infections caused by MDR isolates.

show abstract

Section: Discussionmentioning

confidence: 99%

“…However, colistin-resistant and imipenem-resistant A. baumannii have emerged and these isolates are often multidrug-resistant 1,4,5 .…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial susceptibility of Acinetobacter baumannii isolated from hospital patients

Tunyapanit¹,

Pruekprasert²,

Laoprasopwattana³

et al. 2014

ScienceAsia

View full text Add to dashboard Cite

show abstract

“…Some studies assessed the susceptibility (MICs) of colonies resistant to the first antibiotic that were generated via long-term (Ն24 h) passaging toward a panel of second antibiotics (15). We are not aware of systematic methods to evaluate subpopulation synergy that ac-counted for the time-dependent upregulation and minimized the impact of phenotypic tolerance mechanisms during the first hours of therapy.…”

mentioning

confidence: 99%

Quantifying Subpopulation Synergy for Antibiotic Combinations via Mechanism-Based Modeling and a Sequential Dosing Design

Landersdorfer

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Quantitative modeling of combination therapy can describe the effects of each antibiotic against multiple bacterial populations. Our aim was to develop an efficient experimental and modeling strategy that evaluates different synergy mechanisms using a rapidly killing peptide antibiotic (nisin) combined with amikacin or linezolid as probe drugs. Serial viable counts over 48 h were obtained in time-kill experiments with all three antibiotics in monotherapy against a methicillin-resistant Staphylococcus aureus USA300 strain (inoculum, 10 8 CFU/ml). A sequential design (initial dosing of 8 or 32 mg/liter nisin, switched to amikacin or linezolid at 1.5 h) assessed the rate of killing by amikacin and linezolid against nisin-intermediate and nisin-resistant populations. Simultaneous combinations were additionally studied and all viable count profiles comodeled in S-ADAPT and NONMEM. A mechanism-based model with six populations (three for nisin times two for amikacin) yielded unbiased and precise (r ‫؍‬ 0.99, slope ‫؍‬ 1.00; S-ADAPT) individual fits. The second-order killing rate constants for nisin against the three populations were 5.67, 0.0664, and 0.00691 liter/(mg · h). For amikacin, the maximum killing rate constants were 10.1 h ؊1 against its susceptible and 0.771 h ؊1 against its less-susceptible populations, with 14.7 mg/liter amikacin causing half-maximal killing. After incorporating the effects of nisin and amikacin against each population, no additional synergy function was needed. Linezolid inhibited successful bacterial replication but did not efficiently kill populations less susceptible to nisin. Nisin plus amikacin achieved subpopulation synergy. The proposed sequential and simultaneous dosing design offers an efficient approach to quantitatively characterize antibiotic synergy over time and prospectively evaluate antibiotic combination dosing strategies.

show abstract

“…Rifampicin, considered inactive against Gramnegative bacteria, has emerged as one of the therapeutic options for infections caused by carbapenem-resistant A. baumannii. It is hypothesized that substantial changes in the outer membrane of multi-drug resistant A. baumannii may enable greater access to the target site (Li et al, 2007). When it comes to combination with other antibiotics, colistin is known to induce damage to the cell-wall structures of Gram-negative bacteria, thereby allowing the accelerated penetration of rifampicin (Song et al, 2008;Aoki et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Clinical and microbiological characterization of carbapenem-resistant Acinetobacter baumannii bloodstream infections

Song

Cheong

Choi

et al. 2011

Journal of Medical Microbiology

View full text Add to dashboard Cite

The incidence of carbapenem-resistant Acinetobacter baumannii infection is increasing, which might be associated with high morbidity and mortality among critically ill patients with limited therapeutic options. This study was conducted to evaluate the clinical and microbiological features of carbapenem-resistant A. baumannii bacteraemia. The medical records of 28 adult patients with this bacteraemia admitted to Korea University Guro Hospital, from January 2005 through December 2010, were reviewed. Using the 28 bloodstream isolates, we intended to detect genes encoding carbapenemases, and investigate the inoculum effect on each of the antimicrobial agents rifampicin, imipenem, colistin and tigecycline. With one blood isolate from a patient with pneumonia, rifampicin-inducible resistance was examined using the experimental mouse pneumonia model. Out of 28 carbapenem-resistant A. baumannii bloodstream infections (BIs), the most common primary focus was the central venous catheter (35.7 %) and then the lung (32.1 %). The 30 day overall mortality was 53.6 %; in most cases (80 %) the patients died within 10 days after the onset of the bacteraemia. By univariate analysis, inappropriate antimicrobial therapy (73.3 vs 30.8 %, P50.02), mechanical ventilation (53.3 vs 15.4 %, P50.04) and a high Pitt bacteraemia score (4.9±1.9 vs 2.2±1.2, P,0.01) were statistically significant risk factors for mortality, while only a high Pitt bacteraemia score (odds ratio 2.6; 95 % confidence interval 1.1-6.5) was independently associated with 30 day mortality by multivariate analysis. All 28 isolates had the bla OXA-51 -like gene with upstream ISAbaI, 2 of which additionally had the bla OXA-58 -like gene and the bla OXA-23 -like gene. Inoculum effect and rifampicin inducible resistance were not detected. Considering the rapid progression to death in carbapenemresistant A. baumannii BIs, early empirical antibiotic therapy would be warranted based on the local microbiological data in each hospital.

show abstract

Antibiograms of Multidrug-Resistant Clinical Acinetobacter baumannii: Promising Therapeutic Options for Treatment of Infection with Colistin-Resistant Strains

Cited by 146 publications

References 21 publications

Antimicrobial susceptibility of Acinetobacter baumannii isolated from hospital patients

Antimicrobial susceptibility of Acinetobacter baumannii isolated from hospital patients

Quantifying Subpopulation Synergy for Antibiotic Combinations via Mechanism-Based Modeling and a Sequential Dosing Design

Clinical and microbiological characterization of carbapenem-resistant Acinetobacter baumannii bloodstream infections

Contact Info

Product

Resources

About