Antimicrobial and Antibiofilm Activities of the Fungal Metabolites Isolated from the Marine Endophytes Epicoccum nigrum M13 and Alternaria alternata 13A.

Epicotripeptin (1), a new cyclic tripeptide along with four known cyclic dipeptides (2-5) and one acetamide derivative (6) were isolated from seagrass-associated endophytic fungus Epicoccum nigrum M13 recovered from the Red Sea. Additionally, two new compounds, cyclodidepsipeptide phragamide A (7) and trioxobutanamide derivative phragamide B (8), together with eight known compounds (9-16), were isolated from plant-derived endophyte Alternaria alternata 13A collected from a saline lake of Wadi El Natrun depression in the Sahara Desert. The structures of the isolated compounds were determined based on the 1D and 2D NMR spectroscopic data, HRESIMS data, and a comparison with the reported literature. The absolute configurations of 1 and 7 were established by advanced Marfey's and Mosher's ester analyses. The antimicrobial screening indicated that seven of the tested compounds exhibited considerable (MIC range of 2.5-5 µg/mL) to moderate (10-20 µg/mL) antibacterial effect against the tested Gram-positive strains and moderate to weak (10-30 µg/mL) antibacterial effect against Gram-negative strains. Most of the compounds exhibited weak or no activity against the tested Gram-negative strains. On the other hand, four of the tested compounds showed considerable antibiofilm effects against biofilm forming Gram-positive and Gram-negative strains.

In Vitro Activity of Plazomicin Compared to Amikacin, Gentamicin, and Tobramycin against Multidrug-Resistant Aerobic Gram-Negative Bacilli.

The worldwide spread of multidrug-resistant Enterobacterales is a serious threat to public health. Here, we compared the MICs of plazomicin, amikacin, gentamicin, and tobramycin against 303 multinational multidrug-resistant Gram-negative bacilli. We followed Clinical and Laboratory Standards Institute (CLSI) guidelines and applied CLSI breakpoints as well as those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for amikacin, gentamicin, and tobramycin and of the U.S. Food and Drug Administration for plazomicin. Overall, the highest percentage of susceptible isolates (80.2%) was demonstrated for plazomicin, which had the lowest MIC50 (1 µg/ml) of the aminoglycosides studied. Of the 42 isolates resistant to plazomicin, 34 had MICs of ≥128 µg/ml, with 33 of the 34 having MICs of >128 µg/ml for amikacin, gentamicin, and tobramycin. Among the 42 blaNDM-positive isolates, 35.7% were plazomicin susceptible, with the percentage of isolates susceptible to amikacin being 38.1% or 35.7% when applying the CLSI or EUCAST breakpoint, respectively. The 20 blaOXA-48-like-positive isolates showed 50.0% susceptibility to plazomicin. Among 35 isolates with blaCTX-M as their only characterized resistance mechanism, 68.6% were plazomicin susceptible, while the percentage susceptible to amikacin was 74.3% or 62.9% when applying the CLSI or EUCAST breakpoint, respectively. Among the 117 blaKPC-positive isolates, 94.9% were susceptible to plazomicin, whereas when the CLSI and EUCAST breakpoints were applied, 43.6% and 25.6%, respectively, were susceptible to amikacin; 56.4% and 44.4%, respectively, were susceptible to gentamicin; and 5.1% and 4.3%, respectively, were susceptible to tobramycin.

Norfloxacin salts of carboxylic acids curtail planktonic and biofilm mode of growth in ESKAPE pathogens.

AIMS: To enhance the antimicrobial and antibiofilm activity of norfloxacin against the planktonic and biofilm mode of growth in ESKAPE pathogens using chemically modified norfloxacin salts. METHODS AND RESULTS: Antimicrobial testing, synergy testing and time-kill curve analysis were performed to evaluate antibacterial effect of norfloxacin carboxylic acid salts against ESKAPE pathogens. In vivo efficacy to reduce bacterial bioburden was evaluated in zebrafish infection model. Crystal violet assay and live-dead staining were performed to discern antibiofilm effect. Membrane permeability, integrity and molecular docking studies were carried out to ascertain the mechanism of action. The carboxylic acid salts, relative to parent molecule norfloxacin, displayed two- to fourfold reduction in minimum inhibitory concentration against Staphylococcus aureus and Pseudomonas aeruginosa, in addition to displaying potent bacteriostatic effect against certain members of ESKAPE pathogens. In vivo treatments revealed that norfloxacin tartrate (SRIN2) reduced MRSA bioburden by greater than 1 log fold relative to parent molecule in the muscle tissue. In silico docking with gyrA of S. aureus showed increased affinity of SRIN2 towards DNA gyrase. The enhanced antibacterial effect of norfloxacin salts could be partially accounted by altered membrane permeability in S. aureus and perturbed membrane integrity in P. aeruginosa. Antibiofilm studies revealed that SRIN2 (norfloxacin tartrate) and SRIN3 (norfloxacin benzoate) exerted potent antibiofilm effect particularly against Gram-negative ESKAPE pathogens. The impaired colonization of both S. aureus and P. aeruginosa due to improved norfloxacin salts was further supported by live-dead imaging. CONCLUSION: Norfloxacin carboxylic acid salts can act as potential alternatives in terms of drug resensitization and reuse. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study shows that carboxylic acid salts of norfloxacin could be effectively employed to treat both planktonic- and biofilm-based infections caused by select members of ESKAPE pathogens.

Molecular ß-Lactamase Characterization of Aerobic Gram-Negative Pathogens Recovered from Patients Enrolled in the Ceftazidime-Avibactam Phase 3 Trials for Complicated Intra-abdominal Infections, with Efficacies Analyzed against Susceptible and Resistant Subsets.

The correlation of the clinical efficacy of ceftazidime-avibactam (plus metronidazole) with that of meropenem was evaluated in subjects infected with Gram-negative isolates having characterized ß-lactam resistance mechanisms from the complicated intra-abdominal infection (cIAI) phase 3 clinical trials. Enterobacteriaceae isolates displaying ceftriaxone and/or ceftazidime MIC values of ≥2 µg/ml and Pseudomonas aeruginosa isolates with ceftazidime MIC values of ≥16 µg/ml were characterized for extended-spectrum-ß-lactamase (ESBL) content. Enterobacteriaceae and P. aeruginosa isolates with imipenem and meropenem MIC values of ≥2 and ≥8 µg/ml, respectively, were tested for carbapenemase genes. The primary efficacy endpoint was clinical cure at test of cure (TOC) among the members of the microbiologically modified intention-to-treat (mMITT) population. A total of 14.5% (56/387) and 18.8% (74/394) of patients in the ceftazidime-avibactam and meropenem arms had isolates that met the MIC screening criteria at the baseline visit, respectively. CTX-M variants alone (29.7%; 41/138) or in combination with OXA-1/30 (35.5%; 49/138), most commonly, blaCTX-M group 1 variants (79/90; 87.8%), represented the ß-lactamases most frequently observed among Enterobacteriaceae isolates. Among the patients infected with pathogens that did not meet the screening criteria, 82.2% showed clinical cure in the ceftazidime-avibactam group versus 85.9% in the meropenem group. Among patients infected with any pathogens that met the MIC screening criteria, clinical cure rates at TOC were 87.5% and 86.5% for the ceftazidime-avibactam and meropenem groups, respectively. Ceftazidime-avibactam had clinical cure rates of 92.5% to 90.5% among patients infected with ESBL- and/or carbapenemase-producing Enterobacteriaceae strains at the baseline visit, while meropenem showed rates of 84.9% to 85.4%. The ceftazidime-avibactam and meropenem groups had cure rates of 75.0% and 86.7%, respectively, among patients having any pathogens producing AmpC enzymes. The efficacy of ceftazidime-avibactam was similar to that of meropenem for treatment of cIAI caused by ESBL-producing organisms. (This study has been registered at ClinicalTrials.gov under registration no. NCT01499290 and NCT01500239.).

New polyphenols from a deep sea Spiromastix sp. Fungus, and their antibacterial activities.

Eleven new polyphenols namely spiromastols A-K (1-11) were isolated from the fermentation broth of a deep sea-derived fungus Spiromastix sp. MCCC 3A00308. Their structures were determined by extensive NMR data and mass spectroscopic analysis in association with chemical conversion. The structures are classified as diphenyl ethers, diphenyl esters and isocoumarin derivatives, while the n-propyl group in the analogues is rarely found in natural products. Compounds 1-3 exhibited potent inhibitory effects against a panel of bacterial strains, including Xanthomanes vesicatoria, Pseudomonas lachrymans, Agrobacterium tumefaciens, Ralstonia solanacearum, Bacillus thuringensis, Staphylococcus aureus and Bacillus subtilis, with minimal inhibitory concentration (MIC) values ranging from 0.25 to 4 µg/mL. The structure-activity relationships are discussed, while the polychlorinated analogues 1-3 are assumed to be a promising structural model for further development as antibacterial agents.

Biological activities and DNA interactions of Amanita ovoidea.

CONTEXT: Amanita ovoidea (Bull.) Link (Amanitaceae) is a well-known species due to its pleasant aroma and flavor since ancient times in the worldwide. This species is also known in Turkey and people consume it extensively. OBJECTIVE: To evaluate medicinal importance of A. ovoidea for human health, to explain the effect of mushroom extracts on bacterial DNA, and to find preventive role on bacterial disease. MATERIALS AND METHODS: Chloroform, acetone, and methanol extracts of A. ovoidea were tested for the antimicrobial activities against four Gram-positive bacteria, five Gram-negative bacteria, and yeast using a micro-dilution method. In addition, DNA binding, DNA cleavage activity, and restriction enzyme digestion of the methanol extract of A. ovoidea were examined at different concentrations (40.000-78.125 µg/mL). RESULTS: The highest minimum inhibitory concentration (MIC) value observed against the test micro-organisms was with the chloroform extract (MIC 19.5 µg/mL concentration) against Candida albicans. Other highest antimicrobial effects observed against the test micro-organisms were with the methanol extracts against Bacillus subtilis, Staphylococcus aureus, Listeria monocytogenes, Streptococcus pyogenes, Candida albicans, Klebsiella pneumoniae, Proteus vulgaris, and Salmonella enteritidis (MICs, 78 µg/mL concentrations). All concentrations reduced the mobility of plasmid DNA. BamHI and HindIII targeted specially to supercoils and cut them. Amanita ovoidea extract prevented cutting with HindIII by binding especially to the AA region in open circular DNA. DISCUSSION AND CONCLUSION: Present results demonstrated that A. ovoidea has excellent antimicrobial and antifungal activities by its DNA interaction activity on pBR322.

Antioxidant, antibacterial, and anti-inflammatory activities of standardized brazilin-rich Caesalpinia sappan extract.

CONTEXT: Brazilin is a major active principle of Caesalpinia sappan L. (Leguminosae or Fabaceae). For industry aspects, brazilin-rich extract (BRE) has been prepared and standardized to contain 39% w/w brazilin. BRE may have more advantages than brazilin in term of a lower-cost production process. OBJECTIVES: To investigate the antioxidant, antibacterial, and anti-inflammatory activities of BRE. MATERIAL AND METHODS: BRE was prepared by a simple one-step purification of the crude ethanol extract of C. sappan heartwood (CSE) using a Diaion® HP-20 column. The antioxidant activities were determined using three methods, including DPPH radical scavenging, reducing power, and ß-carotene bleaching assays, at concentration ranges of 1-10, 10-100, and 10-100 µg/mL, respectively. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of BRE (15.6-1000 µg/mL) against Gram-positive and Gram-negative bacteria were determined by the broth microdilution method. Anti-inflammatory activity of BRE (0.1-5 µg/mL) was evaluated as anti-denaturation activity using bovine serum albumin as a substrate. RESULTS AND DISCUSSION: On the basis of ß-carotene bleaching assay, BRE showed antioxidant activity with an EC50 value of 60.5 µg/mL, which was almost equal to that of pure brazilin (52.1 µg/mL). Gram-positive bacteria were more sensitive to all tested samples than Gram-negative bacteria. BRE possessed higher antibacterial activities than CSE, but lower than brazilin. MIC/MBC values of 62.5-125/125 and 250-500/250-500 µg/mL were obtained for BRE against Gram-positive and Gram-negative bacteria, respectively. A low concentration (0.1 µg/mL) of brazilin, BRE, and CSE showed anti-inflammatory activity by inhibiting protein denaturation up to 46.8, 54.1, and 61.9%, respectively.

[Antimicrobial susceptibilityof clinical isolates of aerobic gram-negative bacteria in 2008].

We determined MICs of antibacterial agents against 1145 clinical strains of aerobic Gram-negative bacteria (22 species) isolated at 16 Japanese facilities in 2008. MICs were determined using mostly broth microdilution method and antibacterial activity was assessed. Strains producing extended-spectrum beta-lactamases (ESBL) accounted for 3.8% of Escherichia coli, 2.6% of Klebsiella pneumoniae, 6.8% of Klebsiella oxytoca, 5.5% of Proteus mirabilis and 1.8% of Proteus vulgaris. ESBL produced strains were 6.8% at K. oxytoca that increased compared with 3.2% and 5.5% at P. mirabilis that decreased compared with 18.8% in 2006. Among Haemophilus influenzae, 61.7% that decreased compared with 67.7% in 2006, equaled 58.7% in 2004, were strains when classified by penicillin-binding protein 3 mutation. Against Pseudomonas aeruginosa, the activity of most antibacterial agents was similar to that in 2006. Although two antibacterial agents that tobramycin showed an MIC90 of 1 microg/mL and doripenem showed an MIC90 of 4 microg/mL against P. aeruginosa have potent activity. Of all P. aeruginosa strains, 4.3% were resistant to six agents of nine antipseudomonal agents, that decreased compared to 12.2% in 2004 and 5.7% in 2006. Against other glucose-non-fermentative Gram-negative rods, the activity of most antibacterial agents was similar to that in 2006.

Efficacy of different washing solutions and contact times on the microbial quality and safety of fresh-cut paprika.

The role of different washing solutions and contact times was investigated to determine their use as potential sanitizers for maintaining the microbial quality and food safety of fresh-cut paprika. Samples were cut into small pieces, washed for both 90 and 180 s by different washing solutions: tap water, chlorinated water (100 mg/L and pH 6.5-7), electrolyzed water (pH 7.2) and ozonized water (4 mg/L). Then, samples were packaged in 50 µm polypropylene bags and stored at 5 °C for 12 days, followed by an evaluation of the antimicrobial efficacy of the treatments. Various quality and safety parameters, such as gas composition, color, off-odor, electrical conductivity and microbial numbers, were evaluated during storage. Results revealed insignificant differences in gas composition, and no off-odor was observed in any of the samples during the storage period. However, longer contact time resulted in slightly lower hue angle value than a short one for all washing solutions. Moreover, samples washed with ozone washings showed lower electrolyte leakage than other washing solutions. Samples washed for longer contact time except those washed in ozonized water showed increased microbial numbers during storage. Hence, it has been concluded that longer contact time with ozone has positive effects, whereas the other washing solutions adversely affect the microbial quality and safety aspects of fresh-cut paprika.

Prevalence and Molecular Characterization of Extended Spectrum ß-Lactamase, Plasmid-Mediated Quinolone Resistance, and Carbapenemase-Producing Gram-Negative Bacilli in Burkina Faso.

The spreading of carbapenemase-producing gram-negative bacilli (GNB) must be considered as an "urgent" threat. The aim of this study was to determine the prevalence of extended spectrum ß-lactamase (ESBL), plasmid-mediated quinolone resistance (PMQR), and carbapenemase-producing GNB and to characterize the supporting genes in GNB specimens isolated from patients and healthy volunteers in Burkina Faso. From April to June 2016, carbapenemase-producing GNB screening was performed in 1,230 consecutive clinical specimens, and 158 fecal samples from inpatients and healthy volunteers without digestive pathology at Souro Sanou University Hospital, Bobo Dioulasso. Strains were identified by matrix-assisted laser desorption ionization-time of flight and antimicrobial susceptibility was tested with the disk diffusion method on Müller-Hinton agar. The presence of carbapenemase, ESBL, and PMQR genes was assessed by multiplex PCR. The molecular epidemiological study was performed using multilocus sequence typing analysis. From the 1,230 clinical samples, 443 GNB strains were isolated among which 4 (0.9%) were carbapenemase-producing isolates (Escherichia coli, n = 1; Acinetobacter baumannii, n = 3). Among the 158 fecal samples tested for carbapenemase-producing Enterobacteriaceae carriage, 13 (8.2%) were carbapenemase-producing isolates (E. coli, n = 4; Klebsiella pneumoniae, n = 6; A. baumannii, n = 2; Acinetobacter nosocomialis, n = 1; Acinetobacter bereziniae, n = 1). The strains from the two groups were resistant to broad-spectrum cephalosporins (100% for both), gentamicin (100% and 64.3%), levofloxacin (100% and 85.7%), and to amikacin (0% and 7.1%). The carbapenemase-encoding genes blaNDM-1, blaOxa-58, blaOxa-181, and blaVIM-2 were detected in clinical and in fecal samples. The majority (10/11) of the enterobacterial strains carried also blaCTX-M-15. The majority of the strains belonged to ST692 for E. coli, to ST147 for K. pneumoniae and to ST2 for A. baumannii. This study confirms the presence of carbapenemase-producing GNB in samples from patients and healthy volunteers. More effective active surveillance activities are needed.

Comparative in vitro activity profiles of novel bis-indole antibacterials against gram-positive and gram-negative clinical isolates.

Antimicrobial susceptibilities of 233 gram-positive and 180 gram-negative strains to two novel bis-indoles were evaluated. Both compounds were potent inhibitors of gram-positive bacteria, with MIC(90) values of 0.004 to 0.5 microg/ml. One bis-indole, MBX 1162, exhibited potent activity against all gram-negative strains, with MIC(90) values of 0.12 to 4 microg/ml, even against high-level-resistant pathogens, and compared favorably to all comparator antibiotics. The bis-indole compounds show promise for the treatment of multidrug-resistant clinical pathogens.

In vitro activity of ceftaroline against 623 diverse strains of anaerobic bacteria.

The in vitro activities of ceftaroline, a novel, parenteral, broad-spectrum cephalosporin, and four comparator antimicrobials were determined against anaerobic bacteria. Against Gram-positive strains, the activity of ceftaroline was similar to that of amoxicillin-clavulanate and four to eight times greater than that of ceftriaxone. Against Gram-negative organisms, ceftaroline showed good activity against beta-lactamase-negative strains but not against the members of the Bacteroides fragilis group. Ceftaroline showed potent activity against a broad spectrum of anaerobes encountered in respiratory, skin, and soft tissue infections.

Emerging resistant Gram-negative aerobic bacilli in hospital-acquired infections.

The increasing emergence of serious multidrug-resistant (MDR) Gram-negative infections has led to a new health-care crisis. These infections predominately include MDR Pseudomonas aeruginosa, extended-spectrum beta-lactamase-producing Enterobacteriaceae and MDR Acinetobacter baumannii. These organisms are present in a variety of clinical settings, but there is a distinct paucity of antibiotics to effectively treat these infections. The increasing use of broad-spectrum antibiotics and lack of good stewardship have contributed to the increase in these MDR organisms. This review focuses on the main MDR Gram-negative infections contributing to the current crisis in health care, their mechanisms of resistance and various treatment options for empiric therapy.

[Antimicrobial susceptibility of clinical isolates of aerobic Gram-negative bacteria in 2006].

We determined MICs of antibacterial agents against 1280 clinical strains of aerobic Gram-negative bacteria (19 genus or species) isolated at 16 Japanese facilities in 2006. MICs were determined using mostly broth microdilution method and antibacterial activity was assessed. Strains producing extended-spectrum beta-lactamases (ESBL) accounted for 3.7% of Escherichia coli, 2.7% of Klebsiella spp., and 11.4% of Proteus spp. Notably, 18.8% of Proteus mirabilis was found to produce ESBL higher than 16.7% in 2004. This result was higher extremely than other species. Among Haemophilus influenzae, only 1.2% produced beta-lactamase and 62.8% that increased compared with 57.7% in 2004, were beta-lactamase-negative ampicillin-resistant strains when classified by penicillin-binding protein 3 mutation. Although few antibacterial agents against Pseudomonas aeruginosa have potent activity, only three agents--doripenem, ciprofloxacin, and tobramycin-showed an MIC90 of 4 microg/mL. Of all P aeruginosa strains, 5.7% were resistant to six or more agents of nine antipseudomonal agents, a decrease compared to 8.7% in 2004. Against other glucose-non-fermentative Gram-negative bacteria, the activity of most antibacterial agents was similar to that in 2004.

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents --special references to bacteria isolated between April 2008 and March 2009].

Bacteria isolated from infections in abdominal surgery during the period from April 2008 to March 2009 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 712 strains including 18 strains of Candida spp. were isolated from 173 (80.5%) of 215 patients with surgical infections. Three hundred and sixty-six strains were isolated from primary infections, and 346 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from postoperative infections aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp., and Staphylococcus spp. in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from postoperative infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa, in this order, and from postoperative infections, P aeruginosa was most predominantly isolated, followed by E. coli, Enterobacter cloacae, and K. pneumoniae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Streptococcus constellatus and Gemella morbillorum, and from postoperative infections, E. lenta was most predominantly isolated. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis was the highest from primary infections, followed by Bacteroides thetaiotaomicron, Bacteroides ovatus and Bilophila wadsworthia, and from postoperative infections, B. fragilis was most predominantly isolated, followed by B. thetaiotaomicron, B. wadsworthia and B. ovatus, in this order. In this series, we noticed no vancomycin-resistant methicillin-resistant S. aureus, and Enterococcus spp., nor multidrug-resistant P aeruginosa. We should carefully follow up B. wadsworthia which was resistant to various antibiotics, and also Bacteroides spp. which was resistant to many beta-lactam antibiotics.

Species distribution and antimicrobial susceptibility of gram-negative aerobic bacteria in hospitalized cancer patients.

BACKGROUND: Nosocomial infections pose significant threats to hospitalized patients, especially the immunocompromised ones, such as cancer patients. METHODS: This study examined the microbial spectrum of gram-negative bacteria in various infection sites in patients with leukemia and solid tumors. The antimicrobial resistance patterns of the isolated bacteria were studied. RESULTS: The most frequently isolated gram-negative bacteria were Klebsiella pneumonia (31.2%) followed by Escherichia coli (22.2%). We report the isolation and identification of a number of less-frequent gram negative bacteria (Chromobacterium violacum, Burkholderia cepacia, Kluyvera ascorbata, Stenotrophomonas maltophilia, Yersinia pseudotuberculosis, and Salmonella arizona). Most of the gram-negative isolates from Respiratory Tract Infections (RTI), Gastro-intestinal Tract Infections (GITI), Urinary Tract Infections (UTI), and Bloodstream Infections (BSI) were obtained from leukemic patients. All gram-negative isolates from Skin Infections (SI) were obtained from solid-tumor patients. In both leukemic and solid-tumor patients, gram-negative bacteria causing UTI were mainly Escherichia coli and Klebsiella pneumoniae, while gram-negative bacteria causing RTI were mainly Klebsiella pneumoniae. Escherichia coli was the main gram-negative pathogen causing BSI in solid-tumor patients and GITI in leukemic patients. Isolates of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, and Acinetobacter species were resistant to most antibiotics tested. There was significant imipenem -resistance in Acinetobacter (40.9%), Pseudomonas (40%), and Enterobacter (22.2%) species, and noticeable imipinem-resistance in Klebsiella (13.9%) and Escherichia coli (8%). CONCLUSION: This is the first study to report the evolution of imipenem-resistant gram-negative strains in Egypt. Mortality rates were higher in cancer patients with nosocomial Pseudomonas infections than any other bacterial infections. Policies restricting antibiotic consumption should be implemented to avoid the evolution of newer generations of antibiotic resistant-pathogens.

In vitro susceptibilities of aerobic and facultatively anaerobic gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: 2005 results from Study for Monitoring Antimicrobial Resistance Trends (SMART).

BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) is examining aerobic and facultatively anaerobic gram-negative bacilli (GNB) isolated from intra-abdominal infections. This report summarizes the 2005 annual data. METHODS: During 2005, 76 medical centers in 31 countries in five regions collected intra-abdominal GNB for antimicrobial susceptibility testing using broth microdilution according to the Clinical and Laboratory Standards Institute guidelines. RESULTS: A total of 5,476 unique aerobic and facultatively anaerobic GNB were isolated. Enterobacteriaceae accounted for 86% (4,711) of the total isolates. Among the 12 antimicrobial agents tested, the carbapenems and amikacin were the most reliably active against the Enterobacteriaceae, whereas ampicillin/sulbactam most often was the least active. Escherichia coli was the species most commonly isolated, at 48% (2,654). Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically in 12% (325/2,329) of E. coli and 18% (151/856) of Klebsiella spp. In general, ESBL producers demonstrated lower susceptibility to the majority of the antibiotics than the non-producers; however, ESBL producers usually were susceptible to the carbapenems tested. CONCLUSIONS: In 2005, antibiotic resistance continued to be a problem among GNB isolated from intra-abdominal infections, with the highest resistance rates observed in the Asia/Pacific region. Imipenem-cilastatin, ertapenem, and amikacin were the agents most consistently active in vitro against the Enterobacteriaceae isolated.

Antimicrobial activity of tigecycline against nosocomial pathogens in Pakistan: a multicenter study.

OBJECTIVE: To measure the in-vitro activity of various antibiotics including tigecycline against Gram negative and positive nosocomial aerobic isolates. METHODS: A total of 430 clinical isolates of both Gram positive (143) and negative (287) aerobic bacteria were used from 3 centres during the year 2006 and 2007. Minimum inhibitory concentration (MIC) was determined using broth micro dilution panels. Antibiotic resistance was interpreted using CLSI guidelines. RESULTS: Most of the isolates were resistant to more than one drug. Resistance to tigecycline was not found. Tigecycline (1 microg/ml) had low MIC against organisms tested. CONCLUSION: This data indicates that tigecycline, a new drug in its class, has broad-spectrum in-vitro activity against both Gram negative and positive nosocomial isolates. Therefore, it may be a suitable drug to be used for the treatment of highly resistant nosocomial infections.

Sarecycline: a narrow spectrum tetracycline for the treatment of moderate-to-severe acne vulgaris.

Sarecycline is a novel, narrow-spectrum, once-daily tetracycline-derived oral antibiotic that is FDA-approved in the US to be taken with or without food for moderate-to-severe acne vulgaris for ages 9 years of age and older. Sarecycline possesses anti-inflammatory properties and potent activity against Gram-positive bacteria, including activity against multiple strains of Cutibacterium acnes, while exhibiting minimal activity against enteric aerobic Gram-negative bacteria. Unlike many acne studies, sarecycline was investigated for chest and back acne. Significant reduction in inflammatory lesions was seen at week 12 at 1.5 mg/kg/day of sarecycline, with statistically significant improvement seen as early as week 3. No reports of phototoxicity, dizziness, pseudotumor cerebri or lupus but 1.2% nausea and 1.2% vaginal candidiasis was reported in the pivotal Phase III studies.