Antibiotic resistance

OBJECTIVES: The emergence of antibiotic-resistant bacteria presents a severe challenge to medicine and public health. While bacteriophage therapy is a promising alternative to traditional antibiotics, the general inability of bacteriophages to penetrate eukaryotic cells limits their use against resistant bacteria, causing intracellular diseases like tuberculosis. Bacterial vectors show some promise in carrying therapeutic bacteriophages into cells, but also bring a number of risks like an overload of bacterial antigens or the acquisition of virulence genes from the pathogen...

Carbapenems (imipenem, meropenem, biapenem, ertapenem, and doripenem) are β-lactam antimicrobial agents. Because carbapenems have the broadest spectra among all β-lactams and are primarily used to treat infections by multi-resistant Gram-negative bacteria, the emergence and spread of carbapenemases became a major public health concern. Carbapenemases are the most versatile family of β-lactamases that are able to hydrolyze carbapenems and many other β-lactams. According to the dependency of divalent cations for enzyme activation, carbapenemases can be divided into metallo-carbapenemases (zinc-dependent class B) and non-metallo-carbapenemases (zinc-independent classes A, C, and D)...

Escherichia coli sequence type 131 (ST131) and Klebsiella pneumoniae ST258 emerged in the 2000s as important human pathogens, have spread extensively throughout the world, and are responsible for the rapid increase in antimicrobial resistance among E. coli and K. pneumoniae strains, respectively. E. coli ST131 causes extraintestinal infections and is often fluoroquinolone resistant and associated with extended-spectrum β-lactamase production, especially CTX-M-15. K. pneumoniae ST258 causes urinary and respiratory tract infections and is associated with carbapenemases, most often KPC-2 and KPC-3...

BACKGROUND: Livestock-associated Staphylococcus aureus (LA-SA) has been documented worldwide. However, much remains unknown about LA-SA colonization and infection, especially in rural environments. METHODS: We conducted a large-scale prospective study of 1342 Iowans, including individuals with livestock contact and a community-based comparison group. Nasal and throat swabs were collected to determine colonization at enrollment, and skin infection swabs over 17 months were assessed for S...

Antimicrobial resistance in microbes poses a global and increasing threat to public health. The horizontal transfer of antimicrobial resistance genes was thought to be due largely to conjugative plasmids or transposons, with only a minor part being played by transduction through bacteriophages. However, whole-genome sequencing has recently shown that the latter mechanism could be highly important in the exchange of antimicrobial resistance genes between microorganisms and environments. The transfer of antimicrobial resistance genes by phages could underlie the origin of resistant bacteria found in food...

Increasing incidence of resistance of gram-negative bacteria against even newer antibiotic including carbapenem has generated interest in the old antibiotic colistin, which are being used as salvage therapy in the treatment of multidrug resistant infection. Colistin has excellent bactericidal activity against most gram-negative bacilli. It has shown persist level in the liver, kidney, heart, and muscle; while it is poorly distributed to the bones, cerebrospinal fluid, lung parenchyma, and pleural cavity. Being an old drug, colistin was never gone through the drug development process needed for compliance with competent regulatory authorities that resulted in very much limited understanding of pharmacokinetic (PK) and pharmacodynamic (PD) parameters, such as C max/MIC ratio, AUC/MIC and T > MIC that could predict the efficacy of colistin...

The spread of extended-spectrum β-lactamase (ESBL) genes in Enterobacteriaceae such as Escherichia coli or Klebsiella spp is a major challenge to modern medical practice. Carbapenems are the treatment of choice for serious infections caused by ESBL producers; however, carbapenem resistance has increased globally. ESBL producers might be susceptible to β-lactam-β-lactamase inhibitor (BLBLI) combination antibiotics such piperacillin-tazobactam or amoxicillin-clavulanate. These drugs are frequently avoided in serious infections caused by ESBL producers because of the inoculum effect in-vitro (especially for piperacillin-tazobactam), animal data suggesting inferior efficacy when compared with carbapenems, concerns about pharmacokinetic-pharmacodynamic drug target attainment with standard doses, and poor outcomes shown in some observational studies...

Two isolates, Escherichia coli ella00 and Pseudomonas aeruginosa ella01, obtained from bronchoalveolar lavage, were found to be closely associated in clusters in agar medium. Escherichia coli ella00 was multidrug resistant and CTXM-15 extended-spectrum β-lactamase producer, while P. aeruginosa ella01 was susceptible to all antimicrobials tested. These observations impelled for further studies aimed to understand their microbial interaction. The P. aeruginosa ella01 biofilm-forming capacity was reduced and not affected when it was co-cultured with E...

The rapid onset of resistance reduces the efficacy of most conventional antimicrobial drugs and is a general cause of concern for human well-being. Thus, there is great demand for a continuous supply of novel antibiotics to combat this problem. Bacteria-derived antimicrobial peptides (AMPs) have long been used as food preservatives; moreover, prior to the development of conventional antibiotics, these AMPs served as an efficient source of antibiotics. Recently, peptides produced by members of the genus Bacillus were shown to have a broad spectrum of antimicrobial activity against pathogenic microbes...

Since their reintroduction into the clinic in the 1980s, the polymyxin antibiotics colistin-administered intravenously as an inactive prodrug, colistin methanesulfonate (CMS)-and polymyxin B have assumed an important role as salvage therapy for otherwise untreatable gram-negative infections. However, the emerging pharmacodynamic and pharmacokinetic data on CMS/colistin and polymyxin B indicate that polymyxin monotherapy is unlikely to generate plasma concentrations that are reliably efficacious. Additionally, regrowth and the emergence of resistance with monotherapy are commonly reported even when concentrations exceed those achieved clinically...

BACKGROUND: Variation in prescription of antibiotics in primary care can indicate poor clinical practice that contributes to the increase of resistant strains. General Practitioners (GPs), as a professional group, are expected to have a fairly homogeneous prescribing style. In this paper, we describe variation in prescribing style within and across groups of GPs from six countries. METHODS: Cross-sectional study with the inclusion of 457 GPs and 6394 sore throat patients...

Antibiotic resistance is a global challenge and represents a growing threat on human health worldwide. Wastewater treatment plants (WWTPs) are generally considered as hotspots for control and/or dissemination of antibiotic resistance. The role of antibiotics, antibacterial residues, and heavy metals played on the evolution and spread of antibiotic resistance is still not well understood. Here, the occurrence of antibiotics (i.e., macrolides, tetracyclines, sulfonamides, and quinolones), antibacterial residues (i...

New Delhi metallo β-lactamases are one of the most significant emerging resistance determinants towards carbapenem drugs. Their persistence and adaptability often depends on their genetic environment and linkage. This study reports a unique and novel arrangement of blaNDM-1 gene within clinical isolates of Pseudomonas aeruginosa from a tertiary referral hospital in north India. Three NDM positive clonally unrelated clinical isolates of P. aeruginosa were recovered from hospital patients. Association of integron with blaNDM-1 and presence of gene cassettes were assessed by PCR...

In recent years, carbapenem-resistant Enterobacteriaceae has become endemic in many countries. Because of limited treatment options, the abandoned "old antibiotics", polymyxins, have been reintroduced to the clinic. To evaluate the clinical efficacy of polymyxins in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae, we systemically searched the PubMed, Embase, and Cochrane Library databases and analyzed the available evidence. The Preferred Reporting Items for Systematic reviews and Meta-Analysis statement were followed, and the I(2) method was used for heterogeneity...

Outcomes from methicillin-resistant Staphylococcus aureus (MRSA) infections are relatively poor, at least in part due to the limitations of vancomycin (the current standard treatment for MRSA). Combination antibiotic treatment for MRSA infections is an attractive alternative as it could address most of vancomycin's shortcomings, including poor tissue penetration, slow bacterial killing, and emerging resistance in some strains of MRSA. However, the theoretical promise of combination therapy for MRSA infections has not been borne out in most in vitro and animal studies...

There has been a welcome increase in the number of agents available for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin remains an acceptable treatment option, with moves toward individualized dosing to a pharmacokinetic/pharmacodynamic (PK/PD) target. Numerous practicalities, however, would need to be resolved before implementation. Lipoglycopeptides as a class show excellent in vitro potency. Their long half-lives and complex PKs may preclude these agents being used in critically ill patients...

Pseudomonas aeruginosa is a formidable pathogen in the infection arena. It is able to easily adapt to the environment which it inhabits and can also colonize and invade the human host to cause serious infections. In 2011, it was responsible for 7.1% of all health care-associated infection in the United States. The morbidity and mortality of both blood stream infections and ventilator-associated pneumonia are significant. On a global scale, we have seen the development of not only multidrug resistance but also extensive and pan drug resistance in this organism...

The production of β-lactamase is the principal mechanism by which gram-negative bacteria resist the action of β-lactam antibiotics. In recent decades, there has been an alarming explosion in the diversity, global dissemination, host range, and spectrum of activity of β-lactamases. This has been most clearly reflected by the marked increase in infections caused by bacteria that express extended-spectrum β-lactamases (ESBLs). Some bacterial species possess chromosomally encoded broad-spectrum cephalosporinases (AmpC) that may be expressed at high level by mutational loss of regulatory genes and are intrinsic in some common Enterobacteriaceae, such as Enterobacter spp...

BACKGROUND: Treatment of recalcitrant chronic rhinosinusitis (CRS) is a challenge with increasing antibiotic resistance, leading to re-emergence of topical therapies. The aim of this study was to assess safety and efficacy of topical colloidal silver solution for the treatment of Staphylococcus aureus biofilms in a sheep model. METHODS: In the safety study, normal saline (control) and 30-ppm colloidal silver solution (test) was used to flush the frontal sinuses for 14 days in 8 sheep (4 sheep each)...

Melioidosis is a tropical bacterial infection caused by Burkholderia pseudomallei (B. pseudomallei; Bpm), a Gram-negative bacterium. Current therapeutic options are largely limited to trimethoprim-sulfamethoxazole and β-lactam drugs, and the treatment duration is about 4 months. Moreover, resistance has been reported to these drugs. Hence, there is a pressing need to develop new antibiotics for Melioidosis. Inhibition of enoyl-ACP reducatase (FabI), a key enzyme in the fatty acid biosynthesis pathway has shown significant promise for antibacterial drug development...