multidrug resistant and extremely drug resistant bacteria are we facing the end of the antibiotic era

Antibiotics are one of the most significant advancements of modern medicine. They have changed the prognosis of several bacterial infections, and made possible advanced medical practices associated with a high risk of infectious complications. Unfortunately, antibiotics are affected by the phenomenon of antibiotic resistance, which jeopardizes their efficacy. In recent years, antibiotic discovery and development has been lagging, due to a lower appeal of this sector for the pharmaceutical industry, while antibiotic resistance has continued to evolve with the eventual emergence and dissemination of bacterial strains which are resistant to most available antibiotics and pose a major challenge to antimicrobial chemotherapy. This worrisome scenario, indicated as the "antibiotic resistance crisis", has been acknowledged by Scientific Societies and Public Health Agencies, and is now gathering an increasing attention from the Media and Governments. This article reviews the antibiotic-resistant pathogens which currently pose major problems in terms of clinical and epidemiological impact, and briefly discuss future perspective in this field

Genome-based study of a spatio-temporal cluster of invasive meningococcal disease due to Neisseria meningitidis serogroup C, clonal complex 11

SummaryObjectivesTo describe a spatio-temporal cluster of invasive meningococcal disease (IMD) due to serogroup C meningococci, occurred in a restricted area of Tuscany between January and October 2015, and the results of whole genome sequencing (WGS).MethodsSurveillance activities and public health measures were implemented in the Region. Bacterial isolates from IMD cases were characterized by the National Reference Laboratory of the Istituto Superiore di Sanità (ISS), and WGS was performed on available strains. The kSNP software was used to identify core genome SNPs.ResultsOverall, 28 IMD cases due to meningococcus C were identified up to 31st October, 2015. Of them, 26 were due to meningococcus C:P1.5-1,10-8: F3-6:ST-11 (cc11) and 2 to C:P1.5-1,10-8: F3-6:ST-2780 (cc11). WGS of 13 meningococci isolated during the outbreak occurred in Tuscany in 2015 showed higher similarity when compared with those of 47 C: P1.5-1,10-8: F3-6:ST-11 (cc11) invasive strains from sporadic cases previously detected in Italy.ConclusionsA highly aggressive meningococcal C strain was involved in the cluster of severe IMD occurred in Tuscany, a Region with high vaccine coverage among children. Whether this was due to low herd immunity related to the short duration of vaccine protection needs further investigation

Changing Epidemiology of Extended-Spectrum β-Lactamases in Argentina: Emergence of CTX-M-15

A multicenter survey, carried out in 2010 in Argentina, showed an increased prevalence of extended-spectrum p-lactamase (ESBL)-producing enterobacteria, with some changes in the molecular epidemiology of circulating ESBLs. While enzymes of the CTX-M-2 group remain endemic, the emergence of CTX-M-15 and of enzymes of the CTX-M-8 and CTX-M-9 groups was observed. The CTX-M-15-positive isolates represented 40% of CTX-M producers and included representatives of Escherichia coli ST131 and Klebsiella pneumoniae ST11.Fil: Sennati, S.. Università degli Studi di Siena; ItaliaFil: Santella, G.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; ArgentinaFil: Di Conza, José Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Pallecchi, L.. Università degli Studi di Siena; ItaliaFil: Pino, Marylú. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Ghiglione, Barbara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Rossolini, G.M.. Università degli Studi di Siena; ItaliaFil: Radice, Marcela Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Management of KPC-Producing Klebsiella pneumoniae Infections

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas

In Vitro Synergism of Colistin and N-acetylcysteine against Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is an emerging global opportunistic pathogen, responsible for a wide range of human infections, including respiratory tract infections. Intrinsic multidrug resistance and propensity to form biofilms make S. maltophilia infections recalcitrant to treatment. Colistin is among the second-line options in case of difficult-to-treat S. maltophilia infections, with the advantage of being also administrable by nebulization. We investigated the potential synergism of colistin in combination with N-acetylcysteine (NAC) (a mucolytic agent with antioxidant and anti-inflammatory properties) against S. maltophilia grown in planktonic phase and biofilm. Eighteen S. maltophilia clinical isolates (comprising three isolates from cystic fibrosis (CF) and two trimethoprim-sulfamethoxazole (SXT)-resistant strains) were included. Checkerboard assays showed a synergism of colistin/NAC combinations against the strains with colistin Minimum Inhibitory Concentration (MIC) >2 \ub5g/mL (n = 13), suggesting that NAC could antagonize the mechanisms involved in colistin resistance. Nonetheless, time-kill assays revealed that NAC might potentiate colistin activity also in case of lower colistin MICs. A dose-dependent potentiation of colistin activity by NAC was also clearly observed against S. maltophilia biofilms, also at sub-MIC concentrations. Colistin/NAC combinations, at concentrations likely achievable by topical administration, might represent a valid option for the treatment of S. maltophilia respiratory infections and should be examined further

Isothermal microcalorimetry minimal inhibitory concentration testing in extensively drug resistant Gram-negative bacilli: a multicentre study

Objectives: To evaluate the performance of an isothermal microcalorimetry (IMC) method for determining the MICs among extensively drug-resistant Gram-negative bacilli. Methods: A collection of 320 clinical isolates (n = 80 of each) of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii from Sweden, Spain, Italy and the Netherlands were tested. The MICs were determined using the IMC device calScreener (Symcel, Stockholm, Sweden) and ISO-broth microdilution as the reference method. Essential agreement, categorical agreement, very major errors (VME), major errors (ME) and minor (mE) errors for each antibiotic were determined. Results: Data from 316 isolates were evaluated. Four errors (two ME, one VME, one mE) among 80 K. pneumoniae, six errors (four ME, one VME, one mE) among 79 E. coli, 15 errors (seven VME, three ME, five mE) among 77 P. aeruginosa and 18 errors (12 VME, two ME, four mE) among 80 A. baumannii were observed. Average essential agreement and categorical agreement of the IMC method were 96.6% (95% confidence interval, 94.2–99) and 97.1% (95% confidence interval, 95.4–98.5) respectively when the MICs were determined at the end of 18 hours. Categorical agreement of the IMC method for prediction of MIC by the end of 8 hours for colistin, meropenem, amikacin, ciprofloxacin and piperacillin/tazobactam were 95%, 91.4%, 94%, 95.2% and 93.7% respectively. Conclusions: The IMC method could accurately determine the MICs among extensively drug-resistant clinical isolates of E. coli, K. pneumoniae, P. aeruginosa and A. baumannii isolates

Redesigning β-lactams to combat resistance: summary and conclusions

AbstractThe relentless emergence and spread of antimicrobial resistance warrant an increased awareness of the problem and improved coordination and standardisation of surveillance systems, as well as resistance control strategies. Moreover, this underscores the urgent need for new antibiotics active against the emerging resistant pathogens. Ceftobiprole is a new β-lactam molecule engineered for bactericidal activity against methicillin-resistant staphylococci that also exhibits an extended broad spectrum of activity covering the most clinically important Gram-positive (methicillin-susceptible staphylococci, penicillin-susceptible and -resistant pneumococci, other streptococci and ampicillin-susceptible enterococci) and Gram-negative (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp., Haemophilus spp. and Moraxella spp.) pathogens. Results from studies with experimental infections and from clinical trials support a role for ceftobiprole in treating complicated skin and skin structure infections caused by Gram-positive pathogens, including methicillin-resistant staphylococci, and suggest a potential role for this drug in treating other types of serious infection caused by Gram-positive and Gram-negative pathogens