This research report assessed the differences in resistance rates and antimicrobial usage-versus-susceptibility relationships of Pseudomonas aeruginosa found in various hospital patient care areas. A simplified case control study was also performed to identify patient-specific risk factors associated with cefepime-resistant P. aeruginosa isolates. Last, we determined the consequence of combining mucoid and non-mucoid derived antimicrobial susceptibilities of P. aeruginosa into hospital antibiograms. Overall, susceptibility rates remained lower in the intensive care units (ICUs) compared to the non-ICU patient care areas, except for cefepime over the last time period. Cefepime utilization and antimicrobial-resistance rates among P. aeruginosa isolates had a significant relationship. Decreased meropenem exposure was associated with lower resistance rates relative to cefepime. Risk factors independently associated with cefepime-resistant P. aeruginosa were structural lung disease, ICU admission, recent third generation cephalosporin use, frequent hospital admission and non-urine isolates. Large and statistically significant differences were observed between non-mucoid and combined percent susceptibility data for aminoglycosides. To control antimicrobial resistance and optimize initial empiric antimicrobial therapy, antimicrobial susceptibility and utilization patterns in specific patient care areas should be monitored and risk factors for antimicrobial resistance should be assessed. Mucoid strains of P. aeruginosa should not be included into antimicrobial susceptibility data as this may underestimate activity of most antipseudomonal agents. Full article

A small library of truncated neomycin-conjugates is prepared by consecutive removal of 2,6-diaminoglucose rings, oxidation-reductive amination of ribose, oxidation-conjugation of aminopyridine/aminoquinoline and finally dimerization. The dimeric conjugates were evaluated for antibacterial activity with a unique hemocyanin-based biosensor. Based on the outcome of these results, a second-generation set of monomeric conjugates was prepared and found to display significant antibacterial activity, in particular with respect to kanamycin-resistant E. coli. Full article

Bacterial infections are common in the neonates and are a major cause of morbidity and mortality. Sixty percent of preterm infants admitted to neonatal intensive care units received at least one antibiotic during the first week of life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%, respectively. Kinetic parameters such as the half-life (t_1/2), clearance (Cl), and volume of distribution (Vd) change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. The aim of this study is to review the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate in a single article in order to provide a critical analysis of the literature and thus provide a useful tool in the hands of physicians. The bibliographic search was performed electronically using PubMed, as the search engine, until February 2^nd, 2010. Medline search terms were as follows: pharmacokinetics AND (penicillins OR cephalosporins OR aminoglycosides) AND infant, newborn, limiting to humans. Penicillins, cephalosporins and aminoglycosides are fairly water soluble and are mainly eliminated by the kidneys. The maturation of the kidneys governs the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate. The renal excretory function is reduced in preterms compared to term infants and Cl of these drugs is reduced in premature infants. Gestational and postnatal ages are important factors in the maturation of the neonate and, as these ages proceed, Cl of penicillins, cephalosporins and aminoglycosides increases. Cl and t_1/2 are influenced by development and this must be taken into consideration when planning a dosage regimen with these drugs. More pharmacokinetic studies are required to ensure that the dose recommended for the treatment of sepsis in the neonate is evidence based. Full article

Mycobacterium tuberculosis is an extraordinarily successful human pathogen, infecting one-third of the world’s population and causing nearly two million deaths each year. In this article, current trends in worldwide tuberculosis (TB) incidence, prevalence, and mortality are discussed along with standard TB treatment regimens, characteristics of first-line and second-line anti-tuberculosis drugs, and mechanisms of antibiotic resistance. The global TB emergency has been further exacerbated by extensively drug-resistant (XDR) TB strains that are resistant to our best antibiotics and very difficult to treat. This review also focuses on the emergence of XDR-TB strains, the global health impact, and existing treatment options and outcomes for XDR-TB disease. Finally, this review briefly describes new anti-tuberculosis drugs currently in Phase II clinical evaluations and the impetus for discovering new antibacterial compounds to target drug-resistant M. tuberculosis and improve tuberculosis therapy. Full article

Linezolid, the first oxazolidinone to be used clinically, is effective in the treatment of infections caused by various Gram-positive pathogens, including multidrug resistant enterococci and methicillin-resistant Staphylococus aureus. It has been used successfully for the treatment of patients with endocarditis and bacteraemia, osteomyelitis, joint infections and tuberculosis and it is often used for treatment of complicated infections when other therapies have failed. Linezolid resistance in Gram-positive cocci has been encountered clinically as well as in vitro, but it is still a rare phenomenon. The resistance to this antibiotic has been, until now, entirely associated with distinct nucleotide substitutions in domain V of the 23S rRNA genes. The number of mutated rRNA genes depends on the dose and duration of linezolid exposure and has been shown to influence the level of linezolid resistance. Mutations in associated ribosomal proteins also affect linezolid activity. A new phenicol and clindamycin resistance phenotype has recently been found to be caused by an RNA methyltransferase designated Cfr. This gene confers resistance to lincosamides, oxazolidinones, streptogramin A, phenicols and pleuromutilins, decrease the susceptibility of S. aureus to tylosin, to josamycin and spiramycin and thus differs from erm rRNA methylase genes. Research into new oxazolidinones with improved characteristics is ongoing. Data reported in patent applications demonstrated that some oxazolidinone derivatives, also with improved characteristics with respect to linezolid, are presently under study: at least three of them are in an advanced phase of development. Full article

In general antibiotics interact cooperatively with host defences, weakening and decreasing the virulence of microbial pathogens, thereby increasing vulnerability to phagocytosis and eradication by the intrinsic antimicrobial systems of the host. Antibiotics, however, also interact with host defences by several other mechanisms, some harmful, others beneficial. Harmful activities include exacerbation of potentially damaging inflammatory responses, a property of cell-wall targeted agents, which promotes the release of pro-inflammatory microbial cytotoxins and cell-wall components. On the other hand, inhibitors of bacterial protein synthesis, especially macrolides, possess beneficial anti-inflammatory/cytoprotective activities, which result from interference with the production of microbial virulence factors/cytotoxins. In addition to these pathogen-directed, anti-inflammatory activities, some classes of antimicrobial agent possess secondary anti-inflammatory properties, unrelated to their conventional antimicrobial activities, which target cells of the innate immune system, particularly neutrophils. This is a relatively uncommon, potentially beneficial property of antibiotics, which has been described for macrolides, imidazole anti-mycotics, fluoroquinolones, and tetracyclines. Although of largely unproven significance in the clinical setting, increasing awareness of the pro-inflammatory and anti-inflammatory properties of antibiotics may contribute to a more discerning and effective use of these agents. Full article

Many bacteria grow on surfaces forming biofilms. In this structure, they are well protected and often high dosages of antibiotics cannot clear infectious biofilms. The formation and stabilization of biofilms are mediated by diffusible autoinducers (e.g. N-acyl homoserine lactones, small peptides, furanosyl borate diester). Metabolites interfering with this process have been identified in plants, animals and microbes, and synthetic analogues are known. Additionally, this seems to be not the only way to control biofilms. Enzymes capable of cleaving essential components of the biofilm matrix, e.g. polysaccharides or extracellular DNA, and thus weakening the biofilm architecture have been identified. Bacteria also have mechanisms to dissolve their biofilms and return to planktonic lifestyle. Only a few compounds responsible for the signalling of these processes are known, but they may open a completely novel line of biofilm control. All these approaches lead to the destruction of the biofilm but not the killing of the pathogens. Therefore, a combination of biofilm-destroying compounds and antibiotics to handle biofilm infections is proposed. In this article, different approaches to combine biofilm-controlling compounds and antibiotics to fight biofilm infections are discussed, as well as the balance between biofilm formation and virulence. Full article

Antibiotics have made a significant contribution to improving patient health, but policy makers and health care payers are concerned about the costs of antibiotics in addition to their effectiveness. This paper aims to assess the value of antibiotics by examining incremental cost-utility ratios of antibiotics. Evidence was derived from cost-utility analyses of antibiotics included in the Tufts-New England Center Cost-Effectiveness Analysis Registry through September 2009. The analysis included 85 incremental cost-utility ratios from 23 cost-utility analyses. The findings showed that 38.8% of incremental cost-utility ratios related to dominant antibiotics (i.e., more effective and less costly than the comparator); 45.9% referred to antibiotics that improved effectiveness, but also increased costs; and 15.3% related to dominated antibiotics (i.e., less effective and more costly than the comparator). The median ratio was 748 € per quality-adjusted life year. Using threshold values of 20,000 € per quality-adjusted life year and 50,000 € per quality-adjusted life year, the probability that an antibiotic provides value for money was 64% and 67%, respectively. The current evidence base suggests that the majority of antibiotics provide value for money and that antibiotics can aid decision makers to attain further population health improvements, whilst containing pharmaceutical expenditures. Full article

Lysostaphin is an antimicrobial agent belonging to a major class of antimicrobial peptides and proteins known as the bacteriocins. Bacteriocins are bacterial antimicrobial peptides which generally exhibit bactericidal activity against other bacteria. Bacteriocin production is a self-protection mechanism that helps the microorganisms to survive in their natural habitats. Bacteriocins are currently distributed into three main classes. Staphylococcins are bacteriocins produced by staphylococci, which are Gram-positive bacteria of medical and veterinary importance. Lysostaphin is the only class III staphylococcin described so far. It exhibits a high degree of antistaphylococcal bacteriolytic activity, being inactive against bacteria of all other genera. Infections caused by staphylococci continue to be a problem worldwide not only in healthcare environments but also in the community, requiring effective measures for controlling their spread. Since lysostaphin kills human and animal staphylococcal pathogens, it has potential biotechnological applications in the treatment of staphylococcal infections. In vitro and in vivo studies performed with lysostaphin have shown that this staphylococcin has potential to be used, solely or in combination with other antibacterial agents, to prevent or treat bacterial staphylococcal infectious diseases. Full article

Functional gastrointestinal symptoms such us bloating, fullness, flatulence, diarrhea, and constipation due to irritable bowel syndrome (IBS) were recently attributed to small bowel bacterial overgrowth, a condition depending on the presence of an increased number of bacteria in the small bowel. However, the methodology used to describe this association may be harshly criticized, since it has already been shown to be quite inaccurate. As a result an inappropriate use of antibiotics was consequently generated. In fact, antibiotics could be effective in the treatment of functional complaints, but only in a limited subgroup of patients, characterized by an increase of fermentation at colonic level. In this review, we have examined the papers suggesting a pathophysiological link between IBS and small bowel bacterial overgrowth, underlining its inappropriateness, and put forth our personal view on the rationale for antibiotic use in IBS. Full article