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Ann Clin Microbiol Antimicrob

Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis.

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Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis.

Ann Clin Microbiol Antimicrob. 2016;15(1):41

Authors: Agyeman AA, Ofori-Asenso R

Abstract
BACKGROUND: Treatment options for drug-resistant tuberculosis are still limited. Linezolid has been recommended for treatment of patients with multidrug-resistant (MDR) or extensively-drug-resistant (XDR) tuberculosis, although uncertainties remain regarding its safety and tolerability in these circumstances.
OBJECTIVE: To systematically evaluate the existing evidence regarding the efficacy and tolerability of linezolid in the treatment of MDR or XDR tuberculosis.
METHODS: We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. Searches were conducted in PubMed, Web of Science and EMBASE followed by direct search of abstracts in the International Journal of Tuberculosis and Lung Disease to retrieve primary studies published between January 2000 and January 2016 assessing linezolid efficacy and safety in the treatment of drug-resistant TB. We evaluated the occurrence of outcomes including culture conversion, treatment success and incidence of adverse events such as myelosuppression and neuropathy.
RESULTS: Twenty-three (23) studies conducted in fourteen (14) countries and involving 507 patients were retrieved. Only 1 randomized controlled trial was identified and none of the identified studies involved participants from Africa. The pooled proportion for treatment success was 77.36 % (95 % CI = 71.38-82.83 %, I(2) = 37.6 %) with culture conversion rate determined as 88.45 % (95 % CI = 83.82-92.38 %, I(2) = 45.4 %). There was no strong evidence for both culture conversion (p = 0.0948) and treatment success (p = 0.0695) between linezolid daily doses ≤ 600 and > 600 mg. Only myelosuppression showed a strong statistical significance (p < 0.0001) between dose comparisons. The incidence of neuropathy and other adverse events leading to permanent discontinuation of linezolid also showed no significance upon dose comparisons (p = 0.3213, p = 0.9050 respectively).
CONCLUSION: Available evidence presents Linezolid as a viable option in the treatment of MDR/XDR TB although patients ought to be monitored closely for the incidence of major adverse events such as myelosuppression and neuropathy. Additionally, highly powered randomized controlled trials including participants from endemic regions are urgently needed to better inform the magnitude and significance of Linezolid treatment effect in MDR and XDR TB patients.

PMID: 27334498 [PubMed – in process]

In vitro potency of amikacin and comparators against E. coli, K. pneumoniae and P. aeruginosa respiratory and blood isolates.

In vitro potency of amikacin and comparators against E. coli, K. pneumoniae and P. aeruginosa respiratory and blood isolates.

Ann Clin Microbiol Antimicrob. 2016;15(1):39

Authors: Sutherland CA, Verastegui JE, Nicolau DP

Abstract
BACKGROUND: The purpose of this study was to define the potency of amikacin and comparator agents against a collection of blood and respiratory nosocomial isolates implicated in ICU based pulmonary infections gathered from US hospitals.
METHODS: Minimum inhibitory concentrations of amikacin, aztreonam, cefepime, ceftazidime, ceftolozane/tazobactam, ceftriaxone, ciprofloxacin, imipenem, meropenem, piperacillin/tazobactam and tobramycin were tested against 2460 Gram-negative isolates. Amikacin had 96 % susceptibility against the combined E. coli and K. pneumoniae isolates and 95 % susceptibility against P. aeruginosa.
RESULTS: Ninety-six percent of all of isolates tested were susceptible (i.e., MICs ≤16 mg/L) to amikacin by current laboratory standards which demonstrates a high level of activity to combat infections caused by these organisms including ESBL, MDR, β-lactam and fluoroquinolone resistant strains. Moreover, 99 % of all organisms had amikacin MICs ≤64 mg/L.
CONCLUSIONS: Overall, these data highlight the continued potency of amikacin and suggest that the achievable lung concentrations of approximately 5000 mg/L with the administration of the amikacin by inhalation (Amikacin Inhale, BAY41-6551) will exceed the MICs typically observed for P. aeruginosa, E. coli and K. pneumoniae in the hospital setting.

PMID: 27316973 [PubMed – as supplied by publisher]

Antifungal activity of amphotericin B and voriconazole against the biofilms and biofilm-dispersed cells of Candida albicans employing a newly developed in vitro pharmacokinetic model.

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Antifungal activity of amphotericin B and voriconazole against the biofilms and biofilm-dispersed cells of Candida albicans employing a newly developed in vitro pharmacokinetic model.

Ann Clin Microbiol Antimicrob. 2015;14:21

Authors: El-Azizi M, Farag N, Khardori N

Abstract
BACKGROUND: Candida albicans is a common cause of a variety of superficial and invasive disseminated infections the majority of which are associated with biofilm growth on implanted devices. The aim of the study is to evaluate the activity of amphotericin B and voriconazole against the biofilm and the biofilm-dispersed cells of Candida albicans using a newly developed in vitro pharmacokinetic model which simulates the clinical situation when the antifungal agents are administered intermittently.
METHODS: RPMI medium containing 1-5 X 10(6) CFU/ml of C. albicans was continuously delivered to the device at 30 ml/h for 2 hours. The planktonic cells were removed and biofilms on the catheter were kept under continuous flow of RPMI medium at 10 ml/h. Five doses of amphotericin B or voriconazole were delivered to 2, 5 and 10 day-old biofilms at initial concentrations (2 and 3 μg/ml respectively) that were exponentially diluted. Dispersed cells in effluents from the device were counted and the adherent cells on the catheter were evaluated after 48 h of the last dose.
RESULTS: The minimum inhibitory concentration of voriconazole and amphotericin B against the tested isolate was 0.0325 and 0.25 μg/ml respectively. Amphotericin B significantly reduced the dispersion of C. albicans cells from the biofilm. The log10 reduction in the dispersed cells was 2.54-3.54, 2.30-3.55, and 1.94-2.50 following addition of 5 doses of amphotericin B to 2-, 5- and 10-day old biofilms respectively. The number of the viable cells within the biofilm was reduced by 18 (±7.63), 5 and 4% following addition of the 5 doses of amphotericin B to the biofilms respectively. Voriconazole showed no significant effect on the viability of C. albicans within the biofilm.
CONCLUSION: Both antifungal agents failed to eradicate C. albicans biofilm or stop cell dispersion from them and the resistance progressed with maturation of the biofilm. These findings go along with the need for removal of devices in spite of antifungal therapy in patients with device-related infection. This is the first study which investigates the effects of antifungal agents on the biofilm and biofilm-dispersion of C. albicans in an in vitro pharmacokinetic biofilm model.

PMID: 25885806 [PubMed – indexed for MEDLINE]

The potential of bacteriophage cocktail in eliminating Methicillin-resistant Staphylococcus aureus biofilms in terms of different extracellular matrices expressed by PIA, ciaA-D and FnBPA genes.

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The potential of bacteriophage cocktail in eliminating Methicillin-resistant Staphylococcus aureus biofilms in terms of different extracellular matrices expressed by PIA, ciaA-D and FnBPA genes.

Ann Clin Microbiol Antimicrob. 2015;14(1):49

Authors: Abdulamir AS, Jassim SA, Hafidh RR, Bakar FA

Abstract
BACKGROUND: This study assessed novel approach of using highly lytic phages against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) biofilms with and without biofilm extracellular matrix- disrupting chemical.
METHOD: The resultant phage-based control was assessed in relation to the type of biofilm extracellular matrix namely, polysaccharide intercellular adhesion (PIA) or proteinacious fibronectin-binding protein A (FnBPA). The biofilms were formed in vitro by 24 h incubation of bacteria in 96 wells microtiter plates at room temperature. The formed biofilms were assessed by tissue culture plate (TCP). Moreover, the nature of the biofilm was assessed by scanning electron microscopy (SEM) and PCR assay for detecting PIA genes, ciaA-D and FnBPA genes.
RESULTS: this study showed that applied phages with 0.08 % benezenthonium chloride, for PIA biofilms, and 0.06 % ethanol, for proteinacious FnBPA biofilms, exerted 100 % eradication for MSSA biofilms and about 78 % of MRSA biofilms. The phage-based control of biofilms with chemical adjuvant showed significantly higher efficiency than that without adjuvant (P < 0.05). Moreover, FnBPA biofilms were more common in MRSA than in MSSA while PIA biofilms were more common in MSSA than in MRSA. And the most resistant type of biofilms to phage-based control was FnBPA in MRSA where 50 % of biofilms were reduced but not eradicated completely.
CONCLUSIONS: It is concluded that PIA-disturbing agent and protein denaturing alcohol can increase the efficiency of attacking phages in accessing host cell walls and lysing them which in turn lead to much more efficient MRSA and MSSA biofilm treatment and prevention.

PMID: 26558683 [PubMed – in process]