ABSTRACT
BACKGROUND: The use of combined antibiotic therapy has become an option for infections caused by multidrug-resistant (MDR) bacteria. The time-kill (TK) assay is considered the gold standard method for the evaluation of in vitro synergy, but it is a time-consuming and expensive method. The purpose of this study was to evaluate two methods for testing in vitro antimicrobial combinations: the disk diffusion method through disk approximation (DA) and the agar gradient diffusion method via the MIC:MIC ratio. The TK assay was included as the gold standard. MDR Gram-negative clinical isolates (n = 62; 28 Pseudomonas aeruginosa, 20 Acinetobacter baumannii, and 14 Serratia marcescens) were submitted to TK, DA, and MIC:MIC ratio synergy methods. RESULTS: Overall, the agreement between the DA and TK assays ranged from 20 to 93%. The isolates of A. baumannii showed variable results of synergism according to TK, and the calculated agreement was statistically significant in this species against fosfomycin with meropenem including colistin-resistant isolates. The MIC:MIC ratiometric agreed from 35 to 71% with TK assays. The kappa test showed good agreement for the combination of colistin with amikacin (K = 0.58; P = 0.04) among the colistin-resistant A. baumannii isolates. CONCLUSIONS: The DA and MIC:MIC ratiometric methods are easier to perform and might be a more viable tool for clinical microbiology laboratories.
Subject(s)
Amikacin/pharmacology , Colistin/pharmacology , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria/drug effects , Microbial Sensitivity Tests/methods , Disk Diffusion Antimicrobial Tests , Drug Combinations , Drug Synergism , Gram-Negative Bacteria/genetics , Microbial Viability/drug effectsABSTRACT
Susceptibility of ceftazidime-avibactam and in vitro synergy with meropenem were investigated using disk approximation and time-kill assays against 11 multiresistant Acinetobacter baumannii isolates harboring oxacillinases and 5 Serratia marcescens isolates carrying blaKPC-2 Ceftazidime-avibactam was very active and synergistic with meropenem against multiresistant S. marcescens isolates. On the other hand, only the A. baumannii isolates coharboring blaOXA-23 and blaOXA-117 displayed synergy. The disk approximation technique presented good sensitivity for synergism in S. marcescens infection.
Subject(s)
Anti-Bacterial Agents/pharmacology , Azabicyclo Compounds/pharmacology , Bacterial Proteins/metabolism , Ceftazidime/pharmacology , Meropenem/pharmacology , beta-Lactamases/metabolism , Acinetobacter baumannii/drug effects , Bacterial Proteins/genetics , Drug Combinations , Microbial Sensitivity Tests , Serratia marcescens/drug effects , beta-Lactamases/geneticsABSTRACT
Background: In vitro and clinical studies using parenteral fosfomycin have suggested the possibility of using this drug against infections caused by MDR microorganisms. The aim of this study was to describe a case series of patients treated with fosfomycin who had severe infections caused by pan-drug-resistant Gram-negative bacteria. Methods: We describe a prospective series of cases of hospitalized patients with infections caused by Gram-negative bacteria resistant to ß-lactams and colistin, treated with 16 g of fosfomycin daily for 10-14 days. Isolates were tested for antimicrobial susceptibility and synergism of fosfomycin with meropenem. We tested for resistance genes and performed typing using PCR and WGS. Results: Thirteen patients received fosfomycin (seven immunosuppressed); they had bloodstream infections (n = 11; 85%), ventilator-associated pneumonia (n = 1; 8%) and surgical site infection (n = 1; 8%), caused by Klebsiella pneumoniae (n = 9), Serratia marcescens (n = 3) and Pseudomonas aeruginosa (n = 1). Overall, eight (62%) patients were cured. Using time-kill assays, synergism between fosfomycin and meropenem occurred in 9 (82%) of 11 isolates. Typing demonstrated that K. pneumoniae were polyclonal. Eight patients (62%) had possible adverse events, but therapy was not discontinued. Conclusions: Fosfomycin may be safe and effective against infections caused by pan-drug-resistant Gram-negative microorganisms with different antimicrobial resistance mechanisms and there seems to be synergism with meropenem.
Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Synergism , Fosfomycin/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Negative Bacterial Infections/drug therapy , Meropenem/pharmacology , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Fosfomycin/administration & dosage , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/microbiology , Humans , Male , Meropenem/administration & dosage , Microbial Sensitivity Tests , Microbial Viability/drug effects , Middle Aged , Pneumonia, Ventilator-Associated/drug therapy , Pneumonia, Ventilator-Associated/microbiology , Sepsis/drug therapy , Sepsis/microbiology , Surgical Wound Infection/drug therapy , Surgical Wound Infection/microbiology , Young AdultABSTRACT
We described 27 polyclonal colistin-resistant Enterobacteriaceae (MIC 4-16 µg/mL) infections (12 pneumonia, 12 urinary tract infection (UTI), two Bacteremia, and one skin/soft tissue infection) in which 74% harbored KPC. The isolates were polyclonal, 6 STs were identified and the colistin resistance was due to chromosome mutations. Eight patients with UTI received monotherapy, and combination therapy was given to 19 patients. Overall mortality was 37%. In vitro synergy using time-kill assay was observed in 14 of 19 (74%) isolates tested; the synergistic effect was observed for almost all isolates for the combination of three drugs: colistin, amikacin, and tigecycline. The Kaplan-Meier survival curve showed no significant difference comparing combination therapy with 2, 3, or more drugs and risk factors associated with death were dialysis and shock. These findings reinforce the fact that colistin in combination with other classes of drugs can be useful in treating infections caused by colistin-resistant CRE.
Subject(s)
Amikacin/therapeutic use , Anti-Bacterial Agents/pharmacology , Colistin/therapeutic use , Drug Therapy, Combination , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae/drug effects , Minocycline/analogs & derivatives , Bacterial Proteins/genetics , Drug Resistance, Multiple, Bacterial/genetics , Drug Synergism , Enterobacteriaceae/genetics , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Microbial Sensitivity Tests , Middle Aged , Minocycline/therapeutic use , Pneumonia/drug therapy , Pneumonia/microbiology , Prospective Studies , Soft Tissue Infections/drug therapy , Soft Tissue Infections/microbiology , Tigecycline , Urinary Tract Infections/drug therapy , Urinary Tract Infections/microbiology , beta-Lactamases/geneticsABSTRACT
BACKGROUND: To describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death. METHODS: A prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA). RESULTS: One hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the Bla KPC gene was found in 75.6 % of isolates, and 27 % of isolates were resistant to colistin. Mortality related to infection was 34.6 %, and was higher among patients with pneumonia (61.4 %). Combination therapy was used in 98 (77.2 %), and monotherapy in 22.8 %; 96.5 % of them were UTI patients. Shock, age, and dialysis were independent risk factors for death. There was no difference in infection-related death comparing colistin-susceptible and colistin-resistant infections (p = 0.46); neither in survival rate comparing the use of combination therapy with two drugs or more than two drugs (p = 0.32). CONCLUSIONS: CRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the bla KPC gene was the only carbapenemase found. Shock, dialysis, and age over 60 years were independent risk factors for death.