In- Vitro Activity of Meropenem,a New Carbapenem,Against Imipenem-Resistant Pseudomonas aeruginosa and Xanthomonas maltophilia

Summary

The activity of meropenem, a new carbapenem, as well as imipenem, ceftazidime, aztreonam, tobramycin, amikacin and ciprofloxacin against 18 strains of Xanthomonas maltophilia and 23 strains of Pseudotnonas aeruginosa resistant to imipenem was tested. All strains of X. maltophilia were resistant to both penems. Ceftazidime, tobramycin and ciprofloxacin were the most active antimicrobial agents against this specie. 17% of imipenem-resistant strains of P. aeruginosa were sensitive to meropenem. Ciprofloxacin, amikacin and aztreonam were the most effective agents against these strains.     

In-vitro activity of ciprofloxacin and other beta-lactam antibiotics against gentamicin- and carbenicillin-resistant isolates of Pseudomonas aeruginosa

The susceptibilities of gentamicin- and carbenicillin-resistant clinical isolates of Pseudomonas aeruginosa to newer beta-lactams, netilmicin and ciprofloxacin were studied by a broth microdilution technique. Imipenem, aztreonam and ceftazidime were active against most of the P. aeruginosa strains with minimum inhibitory concentration (MIC) for 90% of the isolates at clinically achievable levels. Piperacillin, azlocillin, cefotaxime, ceftriaxone, cefsulodin, cefoperazone and netilmicin showed poor activity against these organisms, ciprofloxacin exhibited poor activity, inhibiting only 30% of these strains.     

In vitro evaluation of the antimicrobial activity of meropenem in combination with polymyxin B and gatifloxacin against Pseudomonas aeruginosa and Acinetobacter baumannii

The antimicrobial activity of meropenem combined with either polymyxin B or gatifloxacin was evaluated by the checkerboard method against Pseudomonas aeruginosa (10 strains) and Acinetobacter baumannii (10 strains). In addition, the triple combination of polymyxin B, gatifloxacin, and meropenem was also studied as well as the polymyxin B and gatifloxacin combination. A partial synergism interaction between meropenem and polymyxin B was observed for 80% of the A. baumannii strains. In contrast, this combination showed an indifferent effect for 80% of the P. aeruginosa strains tested. The combination of meropenem and gatifloxacin showed synergism only for two strains of A. baumannii, and partial synergism and additive effect for seven strains and indifference for four strains of both species. For the strains of P. aeruginosa, the double combination of polymyxin B and gatifloxacin and the triple combination of meropenem, polymyxin B and gatifloxacin were indifferent for the majority of the strains tested, that is, 90 and 80% respectively.     

Enhanced in-vitro activity of liposome-trapped penicillin-G against Pseudomonas aeruginosa

The growth inhibition of four Pseudomonas aeruginosa strains by liposome-trapped penicillin-G was investigated. There were indications of an association of the efficacy of liposomal penicillin-G with the nature of the 0-antigenic polymeric side chain. Namely, P28-800 and PCF-95 strains, characterized by a rough polysaccharide chain, were the most susceptible, whereas strain P28-0, possessing an intact lipopolysaccharide, resisted the activity of the entrapped drug. Among the rough strains, P642, a beta-lactamase producer, was not affected by the encapsulated drug. The composition of liposomes seems to have a significant impact in arresting the growth of the P. aeruginosa strain.     

Clonal spread of imipenem-resistant Pseudomonas aeruginosa in the intensive care unit of a Turkish hospital.

Pseudomonas aeruginosa may cause life-threatening infections, especially in nosocomial settings. Although carbapenems are considered as one of the most effective alternatives in antipseudomonal therapy, resistance to the carbapenem group of antibacterials is a growing problem. In the first 6 months of 1997, P. aeruginosa isolates that were resistant to almost all antipseudomonal agents including imipenem were recovered from various specimens from intensive, care unit (ICU) patients. Isolates with the same antibiogram profile caused a small outbreak in May 1997. A retrospective case-control study revealed that the major risk factors for infection/colonization with multiresistant P. aeruginosa were prolonged stay in the ICU (p<0.001), previous and lengthy imipenem usage (p<0.001 and p<0.0001, respectively), and mechanical ventilation (p<0.001). Analytical isoelectric focusing of the sonicates prepared from the isolates showed that each isolate produced 1-5 beta-lactamases, enzymes with isoelectric points (pIs) of 5.1, 6.4, 8.5-8.7 being the most prevalent. DNA macrorestriction patterns of imipenem-resistant isolates were distinct from those of the imipenem-sensitive isolates recovered from ICU patients during the same interval and from the environmental isolates (controls). Thus, our results indicate that colonized patients appear to be the major source for cross-contamination of other patients and if imipenem is selected for empirical therapy, emergence of resistant strains should be anticipated and appropriate precautions taken.     

In-vitro susceptibility of clinical isolates of Pseudomonas aeruginosa to beta-lactam and aminoglycoside antibiotics

The in-vitro susceptibilities of 198 isolates of Pseudomonas aeruginosa from clinical human specimens were determined by an agar dilution technique against beta-lactams and aminoglycosides. These isolates were susceptible to imipenem, aztreonam and ceftazidime with the minimum inhibitory concentration (MIC) for 90% of the strains tested being 8, 16 and 8 micrograms/ml, respectively. Aminoglycosides, except amikacin, had low activity (MIC90 greater than 128 micrograms/ml).     

In-vitro activity of ofloxacin against Chlamydia trachomatis

The in-vitro activity of ofloxacin was evaluated against recently isolated Chlamydia trachomatis strains from patients suffering from non-gonococcal urethritis. The minimal inhibitory concentration (MIC) proved to be 1 mg/l against 8 of the 10 strains assayed (the MICs for the other two strains were 0.5 and 2 mg/l). The data obtained confirm that ofloxacin is active against Chlamydia trachomatis at concentrations achievable with the routine dosage regimen. The drug may thus be regarded as potentially useful for the treatment of non-gonococcal urethritis due to Chlamydia.     

In-vitro activity of roxithromycin against Chlamydia trachomatis

Ten Chlamydia trachomatis isolates were tested for their sensitivity to roxithromycin, in comparison with erythromycin and tetracycline. The minimum inhibitory and minimum bactericidal concentrations of roxithromycin ranged from 0.03-0.12 and 0.25-1 microg/ml, respectively.     

Antimicrobial activity of tobramycin against respiratory cystic fibrosis Pseudomonas aeruginosa isolates from Bulgaria

Tobramycin solution for inhalation (TSI) (Novartis pharmaceuticals) is indicated as chronic suppressive treatment for cystic fibrosis (CF) patients aged 6 years and older who are chronically infected by Pseudomonas aeruginosa . Inhaled administration of tobramycin assures high concentrations in the lungs of CF patients, improving the therapeutic ratio over that of parenteral tobramycin levels. Clinical and laboratory Standards institute (CLSI) breakpoints only consider parenteral levels and do not take into account these high antimicrobial concentrations. Therefore, the Spanish meNSURA Group has defined specific values for inhaled tobramycin when testing CF P. aeruginosa isolates (susceptible: minimal inhibitory concentration (MIC) ≤ 64 μg/ml; resistant: ≥ 128 μg/ml). In this study the antimicrobial activity of tobramycin against 120 respiratory CF P. aeruginosa isolates was determined by high-range etest strips (LIOFILCHEM). Applying MENSURA breakpoints, 95% of the strains were categorized as susceptible. With CLSI breakpoints, the susceptibility rate decreased to 92.5%. The activity against non-mucoid P. aeruginosa was higher than that against mucoid isolates (MIC(50)=0.75 and MIC(90)=2 μg/ml vs. MIC(50)=1 and MIC(90)=4 μg/ml). The isolates obtained from patients untreated with TSI were more susceptible to the drug than those from patients receiving maintenance therapy with TSI (MIC(50)=0.75 and MIC(90) =1.5 μg/ml vs. MIC(50)=1.5 and MIC(90)=6 μg/ml). The isolates from patients with long-term P. aeruginosa colonization (over 5 years) revealed the highest tobramycin MICs (MIC(50)=1.00 and MIC(90)>1024 μg/ml). In conclusion, tobramycin has excellent in vitro activity against the studied CF isolates. Some factors such as isolate morphotype, pre-administration of TSI and duration of colonization influence its activity. Whenever TSI is considered for therapy, the CF P. aeruginosa strains categorized as intermediate or resistant to tobramycin according to the CLSI criteria should be recategorized by using the MENSURA interpretive criteria.     

In-vitro and in-vivo activity of roxithromycin against Chlamydia trachomatis

The object of study was the evaluation of both the in-vitro and in-vivo activity of roxithromycin against Chlamydia trachomatis. In-vitro activity against C. trachomatis was achieved by means of minimum inhibitory concentration (MIC) determinations and was recorded as 0.05 mg/l. In vivo activity was tested in 15 of 60 women, attending the Planning Clinic, who were positive for C. trachomatis. Microbiological diagnosis of chlamydial infection was achieved by using a monoclonal direct smear test (Biomerieux-C trachomatis direct IF). All the patients and their partners were treated with 150 mg of roxithromycin twice a day for 15 days. All the patients were requested to avoid unprotected sexual intercourse up to the end of the therapy. The criterion for clinical efficacy was defined as disappearance of clinical signs and the criterion for microbiological efficacy was evidence of eradication of C. trachomatis at the follow-up (mean time: 30 days). A clinical cure and chlamydial eradication was recorded for all the patients at the end of the treatment and at follow-up. Clinical safety was also satisfactory.     

High prevalence of imipenem-resistant and metallo-beta-lactamase-producing Pseudomonas aeruginosa in the Burns Hospital in Tunisia: detection of a novel class 1 integron

Pseudomonas aeruginosa is one of the most important causes of nosocomial infections, and its eradication is very difficult due to its multidrug resistance. The objective of the present study was to characterize the metallo-beta-lactamases (MBLs), integrons, OprD modifications and virulence factors of P. aeruginosa strains isolated from burn patients and to analyze their genetic relatedness by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Sixty-seven P. aeruginosa isolates were recovered from different clinical samples of burn patients hospitalized in the Intensive Care Burn Unit of the Centre de Traumatologie et des Grands Brulés (Ben Arous, Tunisia), and MBLs and alterations in porin OprD were analyzed among imipenem-resistant isolates. Class 1 and 2 integrons were studied by PCR and sequencing of corresponding variable regions. The presence of eight genes involved in the virulence of P. aeruginosa was investigated by PCR. Fourteen of the 36 imipenem-resistant P. aeruginosa (IRPA) isolates (38.8%) were MBLs producers and harbored the bla_VIM-2 gene, in all cases included into class 1 integrons. A new class 1 integron was identified (intI1-bla_OXA-10-aadB-bla_VIM-2-aadB-bla_OXA-10). Five sequence types were detected among IRPA isolates: ST1, ST112, ST238, ST308 and ST395. P. aeruginosa is a major nosocomial pathogen in patients suffering burns, and the spreading of multidrugs resistant and MBL-producing isolates should be controlled in burn units. Moreover, the implantation of infection control guidelines is crucial to decrease the morbidity and mortality of nosocomial infections due to multidrug resistant P. aeruginosa.     

In vitro antibacterial activity of S-4661, a new parenteral carbapenem,against urological pathogens isolated from patients with complicated urinary tract infections

The antibacterial activity of S-4661, a new parenteral carbapenem antibiotic, was assessed against the major urological pathogens isolated from patients with complicated urinary tract infections. S-4661 was slightly less active than imipenem and panipenem, but more active than meropenem and ceftazidime against Gram-positive bacteria. Against Gram-negative bacteria, S-4661 was similar to meropenem, similar to or more effective than imipenem, and more active than panipenem and ceftazidime. Thus S-4661 possesses potent and well-balanced wide-spectrum antibacterial activity against various urological pathogens.     

Microbiological and epidemiological characterization of imipenem-resistant Pseudomonas aeruginosa strains from a Brazilian tertiary hospital: report from the SENTRY Antimicrobial Surveillance Program

OBJECTIVES: To evaluate the antimicrobial susceptibility profile, the genetic similarity, and the mechanisms of carbapenem resistance among imipenem-resistant Pseudomonas aeruginosa isolates collected from a Brazilian tertiary teaching hospital. METHODS: Seventy-eight consecutive samples of P. aeruginosa were evaluated during 2000 and 2001. The antimicrobial susceptibility was evaluated by reference broth microdilution methods and the imipenem-resistant isolates were screened for metallo-beta-lactamase (MbetaL) production throughout disc approximation test and MbetaL Etest strips and isolates with positive screen test result were submitted to PCR assays using primers blaIMP-1, bla VIM-1, blaVIM-2 e blaSPM-1. The genetic similarity of MbetaL-producing strains was evaluated by automated ribotyping for epidemiological typing purpose. RESULTS: Resistance rates were high to the majority of antimicrobial agents tested except polymyxin B, which inhibited all samples at the Clinical and Laboratory Standards Institute breakpoint (< or = 2 microg/ml). Twenty-nine (37.2%) isolates were resistant to imipenem and these isolates showed great genomic variability. MbetaL production was demonstrated in two imipenem-resistant isolates, which were detected using blaSPM-1 and blaIMP-2-specific primers. Sequence analysis revealed the presence of blaSPM-1 and a novel blaIMP-type gene, blaIMP-16. CONCLUSION: The results of this study showed high resistance rates to the majority of antimicrobial agents among P. aeruginosa samples. High imipenem resistance rates were probably due to continuous selection of resistant mutants. The production of MbetaL did not represent a frequent mechanism of carbapenem resistance in this medical center; but a novel MbetaL was identified. Continued antimicrobial surveillance and infection control measures should be emphasized to minimize the emergence and dissemination of antimicrobial resistance.     

In Vitro Activity of Meropenem against Ciprofloxacin-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

Abstract

The in-vitro susceptibilities of a total of 174 ciprofloxacin-resistant Enterobacteriaceae and Pseudomonas aeruginosa were determined. According to the BSAC and NCCLS breakpoints, meropenem, aztreonam, ceftibuten, ceftazidime, imipenem and cefotaxime were the most active (>90%) antimicrobial agents tested against Enterobacteriaceae. Susceptibility of these strains to piperacillin/tazobactam, cefpodoxime and cefixime (84.96%) was higher than that to tobramycin, gentamicin and fosfomycin (50-75%). More than 90% of P. aeruginosa were susceptible to meropenem when both interpretative susceptibility breakpoint criteria were used. Piperacillin, piperacillin/tazobactam and ceftazidime were active against 50-75% of the same strains. Meropenem was the most active antimicrobial tested against all ciprofloxacin-resistant clinical isolates assayed.     

In vitro activity studies of doripenem and two other carbapenems tested against Pseudomonas aeruginosa and other non-fermentative bacilli

Over the past decade, an increasing prevalence of infections caused by non-fermenting Gram-negative bacteria has been reported in many countries. Among these bacteria, Pseudomonas aeruginosa and Acinetobacter baumannii have been associated with high mortality and treatment failures. Treatment options for multidrug-resistant P. aeruginosa and A. baumannii infections are limited to carbapenems in most cases. The mechanisms of carbapenem resistance have been identified in P. aeruginosa and other Gram-negative non-fermenters, including enzyme production, overexpression of efflux pumps, porin deficiencies, and target- site alterations. This article reviews the in vitro activity of doripenem and compares it with that of imipenem and meropenem against a large collection of non-fermenting Gram-negative bacilli, obtained in worldwide surveillance studies between 2000 and 2010. A detailed examination of the available data demonstrate that doripenem has more potent in vitro antibacterial activity against P. aeruginosa and Acinetobacter species compared to other carbapenems. Furthermore, doripenem has a limited ability to select for carbapenem-resistant mutants in vitro.     

In-vitro activity of nisin against clinical isolates of Clostridium difficile

Nisin is a cationic peptide produced by Lactococcus lactis. Its activity against clinical isolates of Clostridium difficile was compared to that of vancomycin and metronidazole by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill studies. Nisin was more active than the other agents, with a MIC90 of 0.256 mg/L and strong bactericidal activity. Nisin may be a promising agent for the management of C. difficile associated diarrhea.     

In-vitro activity of ceftriaxone combined with newer agents against MRSA

In this study, in vitro synergism in combinations of agents as ceftriaxone/dalbavancin, ceftriaxone/linezolid and ceftriaxone/daptomycin against MRSA strains were investigated. Thirty clinical MRSA strains were tested. The minimum inhibitory concentrations of all antibiotics were determined using reference broth microdilution method. In-vitro activities of antibiotics combined against the strains were tested using two-dimensional checkerboard microdilution method. Results were interpreted as follows: synergy = FICI ≤0.5; ‘no interaction’ effect = FICI ?0.5-≤4; antagonism = FICI ?4. The MIC₅₀, MIC₉₀ and MIC_range of ceftriaxone, daptomycin, dalbavancin and linezolid were found as 128, 1024 and 16-2048 mg/L; 1, 1 and 0.5–1 mg/L; 0.12, 0.12 and 0.03–0.12 mg/L; and 1, 2 and 1–2 mg/L, respectively. Our results showed that the frequency of synergistic effects (FICI: ≤0.5) of three combinations were all at the same rate of 77% (23/30). No in vitro antagonism (FICI >4) was observed.     

In-vitro comparative activity of fluconazole and other antifungal agents against Blastoschizomyces capitatus

Blastoschizomyces capitatus represents an emerging fungal pathogen in acute leukemia patients. The susceptibility to amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole of nine clinical isolates was evaluated. A specific medium (high resolution medium) was used for testing fluconazole. This agent and 5-fluorocytosine were at least four- to eight-fold more active than amphotericin B and ketoconazole against all isolates but one.     

In vitro activity of beta-lactam antimicrobial agents in combination with aztreonam tested against metallo-beta-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii

We evaluate the antimicrobial interactions between aztreonam and selected beta-lactams when tested against metallo-beta-lactamase (MbetaL)-producing clinical strains. Ten Pseudomonsa aeruginosa strains, including nine MbetaL-producers (IMP-1, -2, -13, -16, VIM-1, -2, -7, SPM-1 and GIM-1) and five Acinetobacter baumannii strains, including three MbetaL-producers (IMP-1 and -2) were tested using time kill/bactericidal activity methods. Aztreonam at 4, 8 and 16 mg/L was combined with four other beta-lactam antimicrobials (cefepime, ceftazidime, meropenem and piperacillin/tazobactam or ampicillin/sulbactam), each tested at the recognized susceptible breakpoint concentration. Enhanced activity (synergism or additive effect) was observed with four P. aeruginosa strains (IMP-16, VIM-2, SPM-1 and GIM-1 containing strains) and four A. baumannii strains, while antagonism was observed with two P. aeruginosa (IMP-16 and SPM-1-producing strains) and one A. baumannii (non-MbetaL) strain. All other strains showed indifferent interaction (variation of +/- 1 log10 CFU/ml) with any combination evaluated.