Whole-Genome Sequencing To Guide the Selection of Treatment for Drug-Resistant Tuberculosis.
PMID: 30054376 [PubMed - in process] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 31, 2018 Category: Microbiology Authors: Dookie N, Naidoo K, Padayatchi N Tags: Antimicrob Agents Chemother Source Type: research

Reply to Dookie et al., "Whole-Genome Sequencing To Guide the Selection of Treatment for Drug-Resistant Tuberculosis".
Reply to Dookie et al., "Whole-Genome Sequencing To Guide the Selection of Treatment for Drug-Resistant Tuberculosis". Antimicrob Agents Chemother. 2018 Aug;62(8): Authors: Köser CU, Heyckendorf J, Andres S, Olaru ID, Schön T, Sturegård E, Beckert P, Schleusener V, Kohl TA, Hillemann D, Moradigaravand D, Parkhill J, Peacock SJ, Niemann S, Lange C, Merker M PMID: 30054377 [PubMed - in process] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 31, 2018 Category: Microbiology Authors: Köser CU, Heyckendorf J, Andres S, Olaru ID, Schön T, Sturegård E, Beckert P, Schleusener V, Kohl TA, Hillemann D, Moradigaravand D, Parkhill J, Peacock SJ, Niemann S, Lange C, Merker M Tags: Antimicrob Agents Chemother Source Type: research

The Fascinating Echinocandin-Treated Mouse Model of Pneumocystis murina To Understand Pneumocystis jirovecii.
PMID: 30054378 [PubMed - in process] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 31, 2018 Category: Microbiology Authors: Nevez G, Totet A, Damiani C, Le Gal S Tags: Antimicrob Agents Chemother Source Type: research

Reply to Nevez et al., "The Fascinating Echinocandin-Treated Mouse Model of Pneumocystis murina To Understand Pneumocystis jirovecii".
Reply to Nevez et al., "The Fascinating Echinocandin-Treated Mouse Model of Pneumocystis murina To Understand Pneumocystis jirovecii". Antimicrob Agents Chemother. 2018 Aug;62(8): Authors: Cushion MT PMID: 30054379 [PubMed - in process] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 31, 2018 Category: Microbiology Authors: Cushion MT Tags: Antimicrob Agents Chemother Source Type: research

Tolerability of prosthetic joint infection empirical antimicrobial therapy: a prospective cohort study.
Conclusions: The EAT of PJI is associated with an important rate of AE, linked with the use of the vancomycin and piperacillin/tazobactam combination. These results corroborate recent finding suggesting a synergic toxicity of these drugs in comparison with vancomycin-cefepime, which remain to be evaluated in PJI. PMID: 30038037 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 23, 2018 Category: Microbiology Authors: Triffault-Fillit C, Valour F, Guillo R, Tod M, Goutelle S, Lustig S, Fessy MH, Chidiac C, Ferry T, Lyon BJI study group Tags: Antimicrob Agents Chemother Source Type: research

Relative Contribution of the ABC Transporters Cdr1, Pdh1, and Snq2 to Azole Resistance in Candida glabrata.
Abstract The utility of the azole antifungals for the treatment of invasive candidiasis is severely hampered by azole resistance in Candida glabrata This resistance is mediated almost exclusively by activating mutations in the zinc cluster transcription factor Pdr1, which controls the genes encoding the multidrug resistance transporters Cdr1, Pdh1, and Snq2. However, the specific relative contribution of these transporters to resistance is not known. To address this question, the SAT1 flipper method was used to delete CDR1, PDH1, and SNQ2 in a strain of C. glabrata engineered to carry a clinically relevant activat...
Source: Antimicrobial Agents and Chemotherapy - July 23, 2018 Category: Microbiology Authors: Whaley SG, Zhang Q, Caudle KE, Rogers PD Tags: Antimicrob Agents Chemother Source Type: research

Population Pharmacokinetics of the Antimalarial Amodiaquine: A Pooled Analysis to Optimize Dosing.
Abstract Amodiaquine plus artesunate is the recommended antimalarial treatment in many malaria-endemic countries. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over three days. Plasma concentration-time profiles for both parent drug and metabolite were characterized using nonlinear mixed-effects modelling. Amodiaquine pharm...
Source: Antimicrobial Agents and Chemotherapy - July 23, 2018 Category: Microbiology Authors: Ali AM, Penny MA, Smith TA, Workman L, Sasi P, Adjei GO, Aweeka F, Kiechel JR, Jullien V, Rijken MJ, McGready R, Mwesigwa J, Kristensen K, Stepniewska K, Tarning J, Barnes KI, Denti P, WWARN amodiaquine PK study group Tags: Antimicrob Agents Chemother Source Type: research

In Vitro Activity of LYS228, a Novel Monobactam Antibiotic, against Multidrug-resistant Enterobacteriaceae.
Abstract LYS228 is a novel monobactam with potent activity against Enterobacteriaceae LYS228 is stable to metallo-β-lactamases (MBLs) and serine carbapenemases, including Klebsiella pneumoniae carbapenemases (KPCs), resulting in potency against the majority of extended spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE) strains tested. Overall, LYS228 demonstrated potent activity against 271 Enterobacteriaceae strains, including multidrug-resistant isolates. Based upon MIC90 values, LYS228 (MIC90= 1 μg/mL) was ≥32-fold more active against these strains than were ...
Source: Antimicrobial Agents and Chemotherapy - July 23, 2018 Category: Microbiology Authors: Blais J, Lopez S, Li C, Ruzin A, Ranjitkar S, Dean CR, Leeds JA, Casarez A, Simmons RL, Reck F Tags: Antimicrob Agents Chemother Source Type: research

Lysostaphin lysibody leads to effective opsonization and killing of methicillin resistant Staphylococcus aureus in a murine model.
Abstract The cell wall of Gram-positive bacteria contains abundant surface-exposed carbohydrate structures that are highly conserved. While these properties make surface carbohydrates ideal targets for immunotherapy, carbohydrates elicit a poor immune response resulting primarily in low-affinity IgM antibodies. In a previous publication we introduced the lysibody approach to address this shortcoming. Lysibodies are engineered molecules that combine a high-affinity carbohydrate-binding domain from bacterial or bacteriophage origin and an Fc effector portion of a human IgG antibody, thus directing effective immunity...
Source: Antimicrobial Agents and Chemotherapy - July 23, 2018 Category: Microbiology Authors: Raz A, Serrano A, Thaker M, Alston T, Fischetti VA Tags: Antimicrob Agents Chemother Source Type: research

Effects of phage endolysin SAL200 combined with antibiotics on Staphylococcus aureus infection.
Abstract Phages and its derivatives are increasingly reconsidered for the treatment of bacterial infections, due to rising antibiotic resistance. We assessed the anti-staphylococcal effect of the endolysin SAL200 in combination with standard-of-care (SOC) antibiotics. SAL200 activity combined with SOC antibiotics was assessed in vitro by checkerboard and time-kill assays, and in vivo with murine bacteremia and Galleria mellonella infection models. SAL200 reduced SOC antibiotic MICs and showed a ≥3-log10CFU/mL reduction of S. aureus within 30 minutes in time-kill assays. Combinations of SAL200 and SOC antibiotic...
Source: Antimicrobial Agents and Chemotherapy - July 23, 2018 Category: Microbiology Authors: Kim NH, Park WB, Cho JE, Choi YJ, Choi SJ, Jun SY, Kang CK, Song KH, Choe PG, Bang JH, Kim ES, Park SW, Kim NJ, Oh MD, Kim HB Tags: Antimicrob Agents Chemother Source Type: research

The co-identification of mcr-4.6 and blaNDM-1 in a clinical Enterobacter cloacae isolate from China.
Abstract Here we describe the first report of a clinical colistin-resistant ST84 Enterobacter cloacae isolate co-harboring mcr-4.6 (previously named mcr-4.2) and blaNDM-1 from a patient in China. The blaNDM-1-harboring IncX3 plasmid and the novel mcr-4.6-harboring ColE plasmid were completely sequenced. Although this isolate showed high level resistance to colistin, mcr-4.6 plasmid transformation, gene subcloning, susceptibility testing and lipid A matrix-assisted laser desorption ionization mass spectrometry analysis indicate that mcr-4.6 itself doesn't confer resistance to colistin. PMID: 30038043 [PubMed -...
Source: Antimicrobial Agents and Chemotherapy - July 23, 2018 Category: Microbiology Authors: Chavda B, Lv J, Hou M, Chavda KD, Kreiswirth BN, Feng Y, Chen L, Yu F Tags: Antimicrob Agents Chemother Source Type: research

No Resistance to Tenofovir Alafenamide Detected Through 96 Weeks of Treatment in Patients with Chronic Hepatitis B.
Abstract Tenofovir alafenamide (TAF) has shown equivalent efficacy and improved safety profiles for patients with chronic hepatitis B (CHB) compared to tenofovir disoproxil fumarate (TDF). However, limited data are available for its resistance profiles. In 2 clinical trials, 1298 HBeAg-positive and HBeAg-negative patients with CHB were randomized 2:1 and treated with TAF (n=866) or TDF (n=432). Baseline nucleos(t)ide analog resistance substitutions in HBV polymerase/reverse transcriptase (pol/RT) were assessed using INNO-LiPA Multi DR v2/v3. Resistance surveillance was conducted for patients with viremia (HBV DNA ...
Source: Antimicrobial Agents and Chemotherapy - July 23, 2018 Category: Microbiology Authors: Cathcart AL, Chan HL, Bhardwaj N, Liu Y, Marcellin P, Pan CQ, Shalimar, Buti M, Cox S, Parhy B, Zhou E, Martin R, Chang S, Lin L, Flaherty JF, Kitrinos KM, Gaggar A, Izumi N, Lim YS Tags: Antimicrob Agents Chemother Source Type: research

Various sequence types of Enterobacteriaceae carrying blaNDM-5 gene from commercial chicken farms in China.
Abstract A total of 108 meropenem-resistant Enterobacteriaceae isolates were obtained from 1658 rectal swabs collected from 15 unrelated commercial chicken farms in China between 2014 and 2016. These samples yielded sixteen Escherichia coli and two Klebsiella pneumoniae isolates of diverse sequence types carrying a blaNDM-5-bearing IncX3 plasmid. Klebsiella pneumoniae strain sequence type 709 (ST709) has two blaNDM-5-carrying plasmids that were transferred together to E.coli. PMID: 30038045 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 23, 2018 Category: Microbiology Authors: Xiang R, Zhang AY, Ye XL, Kang ZZ, Lei CW, Wang HN Tags: Antimicrob Agents Chemother Source Type: research

In Vivo Efficacy of Meropenem, with a novel non- β-lactam β-lactamase Inhibitor, Nacubactam, against Gram-negative Organisms Exhibiting Various Resistance Mechanisms in a Murine Complicated Urinary Tract Infection Model.
In Vivo Efficacy of Meropenem, with a novel non-β-lactam β-lactamase Inhibitor, Nacubactam, against Gram-negative Organisms Exhibiting Various Resistance Mechanisms in a Murine Complicated Urinary Tract Infection Model. Antimicrob Agents Chemother. 2018 Jul 16;: Authors: Monogue ML, Giovagnoli S, Bissantz C, Zampaloni C, Nicolau DP Abstract Urinary tract infections (UTIs) are a tremendous burden to the healthcare system due to the vast number of infections resulting in antibiotic therapy and/or hospitalization. Additionally, these infections are frequently caused by multi-drug resistant (MDR...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Monogue ML, Giovagnoli S, Bissantz C, Zampaloni C, Nicolau DP Tags: Antimicrob Agents Chemother Source Type: research

Ambroxol induces autophagy and potentiates Rifampin antimycobacterial activity.
Abstract Host-directed therapy (HDT) in tuberculosis is a potential adjunct to antibiotic chemotherapy directed at Mycobacterium tuberculosis A lead compound, ambroxol emerged from a screen for autophagy-inducing drugs. Ambroxol, at clinically-relevant relevant doses, induced autophagy in vitro and in vivo, and promoted mycobacterial killing in macrophages. Ambroxol also potentiated rifampin activity in a murine tuberculosis model. PMID: 30012752 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Choi SW, Gu Y, Peters RS, Salgame P, Ellner JJ, Timmins GS, Deretic V Tags: Antimicrob Agents Chemother Source Type: research

Combination of tenofovir and emtricitabine with efavirenz does not moderate inhibitory effect of efavirenz on mitochondrial function and cholesterol biosynthesis in human T lymphoblastoid cell line.
Abstract Efavirenz (EFV), the most popular non-nucleoside reverse transcriptase inhibitor, has been associated with mitochondrial dysfunction in most in vitro studies. However, in real life the prevalence of EFV-induced mitochondrial toxicity is relatively low. We hypothesized that the agents given in combination with EFV might moderate the effect of EFV on mitochondrial function. To test this hypothesis, we cultured human T lymphoblastoid cell line (CEM cells) with EFV alone and in combination with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) to investigate the effects on mitochondrial respiration ...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Li M, Sopeyin A, Paintsil E Tags: Antimicrob Agents Chemother Source Type: research

Structure-based drug design and characterization of sulfonyl-piperazine benzothiazinone inhibitors of DprE1 from Mycobacterium tuberculosis.
Abstract Macozinone (MCZ) is a tuberculosis (TB) drug candidate that specifically targets the essential flavoenzyme DprE1 thereby blocking synthesis of the cell wall precursor decaprenyl phosphoarabinose (DPA) and provoking lysis of Mycobacterium tuberculosis As part of the MCZ back-up program we exploited structure-guided drug design to produce a new series of sulfone-containing derivatives, 2-sulphonylpiperazin 8-nitro 6-trifluoromethyl 1,3-benzothiazin-4-one, or sPBTZ. These compounds are less active than MCZ but have a better solubility profile and some derivatives display enhanced stability in microsomal assa...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Piton J, Vocat A, Lupien A, Foo C, Riabova O, Makarov V, Cole ST Tags: Antimicrob Agents Chemother Source Type: research

Pharmacodynamics of Daptomycin Against Enterococcus faecium and Enterococcus faecalis in the Murine Thigh Infection Model.
Abstract The Clinical Laboratory Standards Institute (CLSI) daptomycin MIC susceptibility breakpoint for the treatment of enterococcal infections is ≤4 μg/mL. However, patients receiving daptomycin for enterococci with MICs ≤4 μg/mL may experience treatment failures. We assessed the pharmacodynamics of daptomycin against enterococci in a neutropenic murine thigh infection model and determined exposures necessary for bacteriostasis and 1 log10 CFU reduction against Enterococcus faecalis and Enterococcus faecium We further characterized daptomycin efficacy at clinically achievable exposures.Six E. faeciu...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Kidd JM, Abdelraouf K, Asempa TE, Humphries RM, Nicolau DP Tags: Antimicrob Agents Chemother Source Type: research

Murepavadin, a novel antipseudomonal antibiotic: Pharmacokinetics, tolerability and safety in subjects with mild, moderate, and severe renal function impairment.
Abstract This open-label, non-randomized, single-dose, Phase I study evaluated the pharmacokinetics and safety of murepavadin, a novel peptide antibiotic for the treatment of serious Pseudomonas aeruginosa infections. The study was conducted in 32 subjects of either sex in 4 groups (in up to 8 per group) with mild (group A), moderate (group B), severe (group C) renal function impairment or with normal renal function (group D). The degree of renal impairment of the subjects was classified at screening according to the estimated creatinine clearance (CLCr) according to the Cockcroft-Gault equation. All subjects rece...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Dale GE, Halabi A, Petersen-Sylla M, Wach A, Zwingelstein C Tags: Antimicrob Agents Chemother Source Type: research

Clinical Outcomes of the Oral Suspension versus Delayed-release Tablet Formulations of Posaconazole for Prophylaxis of Invasive Fungal Infections.
In conclusion, incidence of breakthrough IFI was low among patients receiving posaconazole prophylaxis, and not significantly different between patients receiving the tablet versus oral suspension formulations. PMID: 30012757 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Furuno JP, Tallman GB, Noble BN, Bubalo JS, Forrest GN, Lewis JS, Bienvenida AF, Holmes CA, Weber BR, McGregor JC Tags: Antimicrob Agents Chemother Source Type: research

Effect of the synthetic bile salt analog CamSA on the hamster model of Clostridium difficile infection.
Abstract Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea and has gained worldwide notoriety due to emerging hypervirulent strains and high incidence of recurrence. We previously reported protection of mice from CDI using the anti-germinant bile salt analog CamSA. Here we describe the effects of CamSA on the hamster model of CDI. CamSA treatment of hamsters showed no toxicity and did not affect the richness or diversity of gut microbiota; however, minor changes in community composition were observed. Treatment of C. difficile-challenged hamsters with CamSA doubled the me...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Howerton A, Seymour CO, Murugapiran SK, Liao Z, Phan JR, Estrada A, Wagner AJ, Mefferd CC, Hedlund BP, Abel-Santos E Tags: Antimicrob Agents Chemother Source Type: research

In vitro minimal inhibitory concentrations of rifampin and ethambutol, and treatment outcome in Mycobacterium avium complex lung disease.
This study investigated the association between treatment outcome and in vitro MICs of rifampin and ethambutol in patients with MAC-LD. Among patients diagnosed with macrolide-susceptible MAC-LD between January 2008 and December 2013, 274 patients treated with a standard regimen for ≥12 months until August 2017 and whose in vitro MIC results were available were enrolled at a tertiary referral center in South Korea. The MIC of antimicrobial agents was determined using the broth microdilution method. The mean age of the included patients was 60.4 years. The overall treatment success rate was 79.6% (218/274 patients) and t...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Kwon BS, Kim MN, Sung H, Koh Y, Kim WS, Song JW, Oh YM, Lee SD, Lee SW, Lee JS, Lim CM, Choi CM, Huh JW, Hong SB, Park S, Shim TS, Chong YP, Jo KW Tags: Antimicrob Agents Chemother Source Type: research

Screening of preselected libraries targeting Mycobacterium abscessus for drug discovery.
Abstract Mycobacterium abscessus (Mabs) is intrinsically resistant to many antimycobacterial antibiotics, which presents serious problems in therapy. Here we describe the development of a novel phenotypic-based microscopic and computerized imaging drug screening approach. A pilot screen of 568 compounds from two libraries identified 17 hits. Eleven of these compounds are described for the first time as active against Mabs The impact of growth media on these compounds' activity was tested revealing that cation-adjusted Mueller Hinton (MHII) broth supports better growth of actively replicating Mabs and improves the ...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Richter A, Strauch A, Chao J, Ko M, Av-Gay Y Tags: Antimicrob Agents Chemother Source Type: research

Broad spectrum and safety of oral treatment with a promising nitrosylated chalcone in murine leishmaniasis.
This study shows the therapeutic potential of an orally active and hepato/nephroprotective chalcone against both cutaneous and visceral leishmaniasis. PMID: 30012761 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Sousa-Batista AJ, Escrivani-Oliveira D, Falcão CAB, Philippon CIMDS, Rossi-Bergmann B Tags: Antimicrob Agents Chemother Source Type: research

Characterization of the AmpC β-lactamase from Burkholderia multivorans.
Characterization of the AmpC β-lactamase from Burkholderia multivorans. Antimicrob Agents Chemother. 2018 Jul 16;: Authors: Becka SA, Zeiser ET, Barnes MD, Taracila MA, Nguyen K, Singh I, Sutton GG, LiPuma JJ, Fouts DE, Papp-Wallace KM Abstract Burkholderia multivorans is a member of the Burkholderia cepacia complex, a group of>20 related species of nosocomial pathogens that commonly infect individuals suffering from Cystic Fibrosis. β-Lactam antibiotics are recommended as therapy for infections due to B. multivorans, which possesses two β-lactamase genes, blapenA and blaAmpC PenA is...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Becka SA, Zeiser ET, Barnes MD, Taracila MA, Nguyen K, Singh I, Sutton GG, LiPuma JJ, Fouts DE, Papp-Wallace KM Tags: Antimicrob Agents Chemother Source Type: research

Impact of Antibiotic Treatment on the Burden of Nasal Staphylococcus aureus Among Hospitalized Patients.
We examined the impact of systemic antibiotics on the burden of nasal Staphylococcus aureus in hospitalized patients. Of 1482 patients, 237 (16%) had nasal methicillin-susceptible S. aureus (MSSA) and 92 (6%) had nasal methicillin-resistant S. aureus (MRSA) on admission. Treatment regimens including agents with inhibitory activity against MRSA or MSSA significantly reduced the burden of carriage, whereas regimens lacking anti-MRSA activity, including fluoroquinolones, promoted MRSA overgrowth. PMID: 30012763 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Kanwar A, Cadnum JL, Jencson AL, Donskey CJ Tags: Antimicrob Agents Chemother Source Type: research

Validation of Heelstick Microsampling to Optimize Micafungin Doses in Neonates and Young Infants.
Abstract Major gaps exist in our knowledge of antimicrobial pharmacokinetics in critically ill neonates and infants that require validated microsampling and bioanalysis methods to support therapeutic drug monitoring. We compared serially collected intravenous (IV) and heel-stick capillary (HSC) sampled plasma concentrations of micafungin (8 mg/kg) in eight infants born preterm, with systemic candidiasis. The mean (SD) micafungin AUCinf was 316 (65.0) h·mg/L based on HSC concentrations that strongly correlated (R2= 0.92) with IV values to support dose adjustment. PMID: 30012764 [PubMed - as supplied by ...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Auriti C, Goffredo BM, Ronchetti MP, Piersigilli F, Cairoli S, Bersani I, Dotta A, Pai MP Tags: Antimicrob Agents Chemother Source Type: research

Evaluation of Oritavancin in Combination with Rifampin, Gentamicin or Linezolid Against Prosthetic Joint Infection-Associated Methicillin-Resistant Staphylococcus aureus Biofilms by Time-Kill Assays.
Abstract The anti-biofilm activity of oritavancin in combination with rifampin, gentamicin or linezolid was evaluated against ten prosthetic joint infection (PJI) related methicillin-resistant Staphylococcus aureus (MRSA) by time-kill assays. Oritavancin combined with rifampin demonstrated statistically significant bacterial reductions compared to either antimicrobial alone for all ten isolates (P ≤0.001), with synergy being observed for 80% (8/10) of the isolates. Oritavancin and rifampin combination therapy may be an option for treating MRSA PJI. PMID: 30012765 [PubMed - as supplied by publisher] (Source...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Yan Q, Karau MJ, Raval YS, Patel R Tags: Antimicrob Agents Chemother Source Type: research

Significantly improved pharmacokinetics enhances in vivo efficacy of APX001 against echinocandin and multidrug resistant Candida isolates in a mouse model of invasive candidiasis.
Abstract APX001 is a first-in-class, intravenous and orally available broad-spectrum antifungal agent in clinical development for the treatment of life-threatening invasive fungal infections. The half-life of APX001A, the active moiety of APX001, is significantly shorter in mice than in humans (1.4 - 2.75 h in mice vs 2 - 2.5 days in humans), making exploration of efficacy in mouse models difficult. With pre-treatment of 1-aminobenzotriazole (ABT), a non-specific cytochrome P450 inhibitor, greatly increased plasma exposure of APX001A was observed in different mice strains of both genders. As a consequence, 26 mg/k...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Zhao Y, Lee MH, Paderu P, Lee A, Jimenez-Ortigosa C, Park S, Mansbach RS, Shaw KJ, Perlin DS Tags: Antimicrob Agents Chemother Source Type: research

Increased Doses Lead to Higher Drug Exposures of Levofloxacin for the Treatment of Tuberculosis.
Abstract Patients with multidrug-resistant tuberculosis in Peru and South Africa were randomized to weight-banded nominal doses of 11, 14, 17 or 20 mg/kg/day levofloxacin (minimum 750 mg) in combination with other second-line agents. 101 patients were included in noncompartmental pharmacokinetic analyses. Respective median AUC0-24 were 109.49, 97.86, 145.33 and 207.04 h*mcg/ml. Median Cmax were 11.90, 12.02, 14.86, and 19.17 mcg/ml. Higher levofloxacin doses, up to 1500 mg daily, resulted in higher exposures. ClinicalTrials.gov Identifier: NCT01918397. PMID: 30012767 [PubMed - as supplied by publisher] (Sourc...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Peloquin CA, Phillips PPJ, Mitnick CD, Eisenach K, Patientia RF, Lecca L, Gotuzzo E, Gandhi NR, Butler D, Diacon AH, Martel B, Santillan J, Hunt KR, Vargas D, von Groote-Bidlingmaier F, Seas C, Dianis N, Moreno-Martinez A, Kaur P, Horsburgh CR Tags: Antimicrob Agents Chemother Source Type: research

Comprehensive substrate characterization of 22 antituberculosis drugs for multiple solute carrier (SLC) uptake transporters, in vitro.
In conclusion, this is the first study that, demonstrated 22 antituberculosis drugs interactions with transporters. This study will be helpful for mechanistic understanding of the disposition, drug-drug interactions and pharmacokinetics of these antituberculosis drugs. PMID: 30012768 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Parvez MM, Kaisar N, Shin HJ, Lee YJ, Shin JG Tags: Antimicrob Agents Chemother Source Type: research

Impact of an antifungal stewardship programme in a tertiary respiratory medicine setting: A prospective real-world study.
Abstract There has been an increase in fungal infections in patients with chronic lung disease over the past decades, which is associated with rapidly increasing costs to healthcare systems.An antifungal stewardship team was introduced to a tertiary cardiopulmonary hospital, consisting of a medical mycologist and pharmacy support providing weekly stewardship ward rounds, twice monthly multidisciplinary team meetings and a dedicated weekly outpatient clinic. A database was set up to record the activity of the stewardship team.During the first eighteen months of implementation the antifungal stewardship team had revie...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Nwankwo L, Periselneris J, Cheong J, Thompson K, Darby P, Leaver N, Schelenz S, Armstrong-James D Tags: Antimicrob Agents Chemother Source Type: research

Novel potent capsid assembly modulators regulate multiple steps of the Hepatitis B virus life-cycle.
In this study, novel CAMs JNJ-827 and JNJ-890, were found to be potent inhibitors of HBV replication with a respective half maximal effective concentration of 4.7 and 66 nM in HepG2.117 cells. Antiviral profiling in differentiated HepaRG (dHepaRG) cells and primary human hepatocytes (PHH) revealed that these compounds efficiently inhibited HBV replication, as well as de novo establishment of cccDNA. In addition to these two known effects of CAMs, we observed for the first time that a CAM, here JNJ-827, when added post-infection for a short-term period, significantly reduced HBeAg secretion without affecting the levels of c...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Lahlali T, Berke JM, Vergauwen K, Foca A, Vandyck K, Pauwels F, Zoulim F, Durantel D Tags: Antimicrob Agents Chemother Source Type: research

In silico typing and comparative genomic analysis of IncFIIK plasmids: insights into the evolution of replicons, plasmid backbones and resistance determinant profiles.
This study provides insights into the evolution and structures of IncFIIK plasmids. PMID: 30012771 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Bi D, Zheng J, Li JJ, Sheng ZK, Zhu X, Ou HY, Li Q, Wei Q Tags: Antimicrob Agents Chemother Source Type: research

Extended Duration MK-8591-Eluting Implant as a Candidate for HIV Treatment and Prevention.
Abstract Adherence remains a major hurdle to the success of daily oral drug regimens for the treatment and prevention of HIV infection. Long-acting drug formulations requiring less frequent dosing offer an opportunity to improve adherence and allow for more forgiving options with regard to missed doses. Administration of long-acting formulations in a clinical setting enables healthcare providers to directly track adherence. MK-8591 (4'-ethynyl-2-fluoro-deoxyadenosine; EFdA) is an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) drug candidate under investigation as part of a regimen...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Barrett SE, Teller RS, Forster SP, Li L, Mackey MA, Skomski D, Yang Z, Fillgrove KL, Doto GJ, Wood SL, Lebron J, Grobler JA, Sanchez RI, Liu Z, Lu B, Niu T, Sun L, Gindy ME Tags: Antimicrob Agents Chemother Source Type: research

Effective treatment of the Mycobacterium avium subsp hominissuis and Mycobacterium abscessus sp. infections in macrophages, biofilm and in mice using Liposomal ciprofloxacin.
In this report, we evaluate novel formulations of liposome-encapsulated ciprofloxacin (liposomal ciprofloxacin) in vitro and in vivo Efficacy was examined in macrophages, biofilms and in vivo using intranasal instillation mouse models against Mycobacterium avium and Mycobacterium abscessus Liposomal ciprofloxacin was significantly more active than free ciprofloxacin in macrophages and biofilms against both pathogens. When evaluated in vivo, the liposomal ciprofloxacin formulations were associated with significant decreases in bacterial loads in the lung of animals infected with M. avium and M. abscessusIn summary, topical ...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Blanchard JD, Elias V, Cipolla D, Gonda I, Bermudez LE Tags: Antimicrob Agents Chemother Source Type: research

In vitro antiviral activity of cabotegravir against HIV-2.
We examined the antiviral activity of the integrase inhibitor (INI) cabotegravir against HIV-2 isolates from INI-naïve individuals. HIV-2 was sensitive to cabotegravir in both single-cycle and spreading infection assays, with EC50 values in the low to sub-nanomolar range; comparable results were obtained for HIV-1 in both assay formats. Our findings suggest that cabotegravir should be evaluated in clinical trials as a potential option for ART and PrEP in HIV-2-prevalent settings. PMID: 30012774 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Smith RA, Wu VH, Zavala CG, Raugi DN, Ba S, Seydi M, Gottlieb GS, University of Washington-Dakar HIV-2 Study Group Tags: Antimicrob Agents Chemother Source Type: research

Validation of a dried blood spot ceftriaxone assay in Papua New Guinean children with severe bacterial infections.
In this study we aimed to demonstrate the validity of a DBS ceftriaxone assay in a PK study of children from Papua New Guinea (PNG) with severe illness, a setting in which healthcare resources are limited and anemia is common.Methods: Using a previously validated liquid chromatography-mass spectroscopy (LC-MS/MS) assay, serial plasma and DBS ceftriaxone concentrations were measured in PNG children aged 5-10 years with acute bacterial meningitis or severe pneumonia. The concentration-time data were incorporated into population PK models.Results: Ten children were recruited with an admission hematocrit of 0.22-0.52. Raw data...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Mukap M, Sprod C, Tefuarani N, Laman M, Page-Sharp M, Salman S, Moore BR, Batty KT, Davis TME, Manning L Tags: Antimicrob Agents Chemother Source Type: research

Microdialysis Study of Aztreonam-Avibactam Distribution in Peritoneal Fluid and Muscle of Rats with or without Experimental Peritonitis.
Abstract The purpose of this study was to investigate aztreonam (ATM) and avibactam (AVI) distribution in intraperitoneal fluid and muscle interstitial fluid by microdialysis in rats, with or without peritonitis, and to compare the unbound concentrations in tissue with the unbound concentrations in blood. Microdialysis probes were inserted into the jugular vein, hind leg muscle and peritoneal cavity of control rats (n = 5) and rats with intra-abdominal sepsis (n = 9) induced by cecal ligation and punctures. ATM and AVI probe recoveries in each media were determined for both molecules in each rat by retrodialysis b...
Source: Antimicrobial Agents and Chemotherapy - July 16, 2018 Category: Microbiology Authors: Chauzy A, Lamarche I, Adier C, Couet W, Marchand S Tags: Antimicrob Agents Chemother Source Type: research

Efficacy of short-course antibiotic treatments for community-acquired pneumonia in adults: A systematic review and meta-analysis.
Conclusion: In CAP, short-course antibiotic treatment (≤6 days) is equally effective and potentially superior, in terms of mortality and serious adverse events, compared to longer-course treatment. PMID: 29987137 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 9, 2018 Category: Microbiology Authors: Tansarli GS, Mylonakis EE Tags: Antimicrob Agents Chemother Source Type: research

β-lactam dosage regimens in septic patients with augmented renal clearance.
β-lactam dosage regimens in septic patients with augmented renal clearance. Antimicrob Agents Chemother. 2018 Jul 09;: Authors: Jacobs A, Taccone FS, Roberts JA, Jacobs F, Cotton F, Wolff F, Creteur J, Vincent JL, Hites M Abstract Augmented renal clearance is commonly observed in septic patients and may result in insufficient β-lactam serum concentrations. The aims of this study were to evaluate potential correlations between drug concentrations or total body clearance of β-lactam antibiotics and measured creatinine clearance, and to quantify the need for drug dosage adjustments in sept...
Source: Antimicrobial Agents and Chemotherapy - July 9, 2018 Category: Microbiology Authors: Jacobs A, Taccone FS, Roberts JA, Jacobs F, Cotton F, Wolff F, Creteur J, Vincent JL, Hites M Tags: Antimicrob Agents Chemother Source Type: research

Bioequivalence of a Fixed-Dose Combination Tablet of the Complete 2-Drug Regimen Dolutegravir and Rilpivirine for the Treatment of HIV-1 Infection.
Conclusions: The dolutegravir/rilpivirine fixed-dose combination tablet is bioequivalent to a combination of separate tablets and no new safety signals emerged. PMID: 29987139 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 9, 2018 Category: Microbiology Authors: Mehta R, Wolstenholme A, Di Lullo K, Fu C, Joshi S, Crauwels H, Givens N, Vanveggel S, Wynne B, Adkison K Tags: Antimicrob Agents Chemother Source Type: research

Repurposing strategy of atorvastatin against Trypanosoma cruzi: in vitro monotherapy and combined therapy with benznidazole exhibits synergistic trypanocidal activity.
Abstract Statins are inhibitors of cholesterol synthesis but other biological properties, like antimicrobial effects, have been assigned leading to the designation of their pleiotropic aspect. Our goal was investigate the activity and selectivity of atorvastatin (AVA) against T. cruzi using in vitro models aiming more effective and safer therapeutic options through drug repurposing proposals under monotherapy and in combination with benznidazole (BZ). Phenotypic screening used different strains (Tulahuen (DTU VI) and Y (DTU II)) and forms (intracellular forms, bloodstream and tissue-derived trypomastigotes) of the...
Source: Antimicrobial Agents and Chemotherapy - July 9, 2018 Category: Microbiology Authors: Araujo-Lima CF, Peres RB, Silva PB, Batista MM, Aiub CAF, Felzenszwalb I, Soeiro MNC Tags: Antimicrob Agents Chemother Source Type: research

Synergy between circular bacteriocin AS-48 and ethambutol against Mycobacterium tuberculosis.
ueda M, Aínsa JA Abstract The increasing incidence of multi-drug resistant Mycobacterium tuberculosis and the very few drugs available for treatment is promoting the discovery and development of new molecules that could help in the control of this disease. Bacteriocin AS-48 is an antibacterial peptide produced by Enterococcus faecalis, active against several Gram-positive bacteria. We have found that AS-48 was active against Mycobacterium tuberculosis, including H37Rv and other reference and clinical strains, and also against some non-tuberculous clinical mycobacterial species. The combination of AS-48 with...
Source: Antimicrobial Agents and Chemotherapy - July 9, 2018 Category: Microbiology Authors: Aguilar-Pérez C, Gracia B, Rodrigues L, Vitoria A, Cebrián R, Deboosère N, Song OR, Brodin P, Maqueda M, Aínsa JA Tags: Antimicrob Agents Chemother Source Type: research

Pharmacokinetics of ciprofloxacin in children with complicated urinary tract infection: results of a multicenter population pharmacokinetic study.
Abstract Resistance rates for ciprofloxacin, which is labeled for treating complicated urinary tract infections in children, are rapidly rising. As there is limited knowledge on developmental pharmacology of ciprofloxacin, the primary aim of this study was to develop a population pharmacokinetic model for ciprofloxacin in children treated for complicated urinary tract infections. Children to whom ciprofloxacin was prescribed, intravenous (10-15 mg/kg body weight every 12 h) or per os (15-20 mg/kg every 12 h), were enrolled. 108 Serum and 119 urine samples were obtained during 10 intravenous and 13 oral courses of ...
Source: Antimicrobial Agents and Chemotherapy - July 9, 2018 Category: Microbiology Authors: Meesters K, Michelet R, Mauel R, Raes A, Van Bocxlaer J, Vande Walle J, Vermeulen A Tags: Antimicrob Agents Chemother Source Type: research

Role of ascorbic acid as supporting in the therapeutic of chagas disease: benefits in the association with low dose of benznidazole.
ROLE OF ASCORBIC ACID AS SUPPORTING IN THE THERAPEUTIC OF CHAGAS DISEASE: BENEFITS IN THE ASSOCIATION WITH LOW DOSE OF BENZNIDAZOLE. Antimicrob Agents Chemother. 2018 Jul 09;: Authors: Providello MV, Carneiro ZA, Portapilla GB, do Vale GT, Camargo RS, Tirapelli CR, de Albuquerque S Abstract The acute phase of Chagas disease (CD) is characterized by high parasitic proliferation and intense inflammation, exacerbating the generation of reactive oxygen and nitrogen species (ROS and RNS, respectively). These reactive molecules are also increased by the metabolism of the nitroheterocyclic compounds Benznida...
Source: Antimicrobial Agents and Chemotherapy - July 9, 2018 Category: Microbiology Authors: Providello MV, Carneiro ZA, Portapilla GB, do Vale GT, Camargo RS, Tirapelli CR, de Albuquerque S Tags: Antimicrob Agents Chemother Source Type: research

Malaria Prophylaxis Using Naphthoquine-Azithromycin Combination: Randomized, Double-Blind, Placebo-Controlled Studies to Assess Safety and Protective Efficacy in Southeast Asia.
Abstract New prophylactic drugs against malaria infections are urgently needed. We conducted randomized, double-blind, placebo-controlled, phase 2 trials of a new antimalarial drug combination, naphthoquine-azithromycin (NQAZ), to determine its safety and protective efficacy in a low-endemicity area of Southeast Asia. In the first trial, 127 healthy volunteers were randomized to receive two single-doses of either 400 mg of NQAZ (200 mg of each drug), 800 mg of NQAZ (400 mg of each drug), or placebo on day 0 and day 30. Weekly follow-ups were performed for two months, and physical and clinical laboratory exams were...
Source: Antimicrobial Agents and Chemotherapy - July 9, 2018 Category: Microbiology Authors: Yang H, Wang J, Liu H, Li X, Nie R, Li C, Wang H, Wang Q, Cao Y, Cui L Tags: Antimicrob Agents Chemother Source Type: research

Effect of cumulative intravenous voriconazole dose on renal function in hematological patients.
Abstract The intravenous voriconazole (VRC) is formulated by the incorporation of sulfobutylether-β-cyclodextrin (SBECD), which may accumulate to adversely affect renal function. However, the effect of long-term use of intravenous VRC on renal function is unclear. Our retrospective data confirmed that worsening of renal function was significantly associated with cumulative dose of intravenous VRC (≥ 400mg/kg), suggesting that a higher cumulative dose of intravenous VRC was a risk factor for renal dysfunction. PMID: 29987145 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - July 9, 2018 Category: Microbiology Authors: Yasu T, Konuma T, Kuroda S, Takahashi S, Tojo A Tags: Antimicrob Agents Chemother Source Type: research

Echinocandin treatment of Candida albicans biofilms enhances neutrophil extracellular trap (NET) formation.
Abstract The nosocomial pathogen Candida albicans forms biofilms on medical devices that persist in the face of antifungals and host defenses. Echinocandins, the most effective anti-biofilm drugs, have recently been shown to augment the activity of neutrophils against biofilms through an unknown mechanism. Here we show that treatment of C. albicans biofilms with sub-inhibitory concentrations of echinocandins promotes the formation of neutrophil extracellular traps (NETs), structures of DNA, histones, and antimicrobial proteins with antifungal activity. PMID: 29987146 [PubMed - as supplied by publisher] (Sourc...
Source: Antimicrobial Agents and Chemotherapy - July 9, 2018 Category: Microbiology Authors: Hoyer AR, Johnson CJ, Hoyer MR, Kernien JF, Nett JE Tags: Antimicrob Agents Chemother Source Type: research

Efficiency of Target Larvicides is Conditioned by ABC-Mediated Transport in the Zoonotic Nematode Anisakis pegreffii.
ina C Abstract Anisakiasis is among the most significant emerging food-borne parasitoses contracted through consumption of thermally unprocessed seafood harbouring infective Anisakis spp. larvae. The efficacy of the currently applied anthelminthic therapy in humans and in model organisms has not proven sufficient, so alternative solutions employing natural compounds combined with chemical inhibitors should be explored. By testing toxicity of the natural monoterpenes nerolidol and farnesol, and conventional anthelminthics abamectin and levamisole, in the presence/absence of MK-571 and Valspodar that inhibit the ABC...
Source: Antimicrobial Agents and Chemotherapy - July 9, 2018 Category: Microbiology Authors: Mladineo I, Trumbić Ž, Hrabar J, Vrbatović A, Bušelić I, Ujević I, Roje-Busatto R, Babić I, Messina C Tags: Antimicrob Agents Chemother Source Type: research