beta-Lactamase-based biosensor for the electrochemical determination of benzylpenicillin in milk

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hypersensitivity reactions to non beta-lactam antimicrobial agents, a statement of the WAO special committee on drug allergy

Antibiotics are used extensively in the treatment of various infections. Consequently, they can be considered among the most important agents involved in adverse reactions to drugs, including both allergic and non-allergic drug hypersensitivity [J Allergy Clin Immunol 113:832–836, 2004]. Most studies published to date deal mainly with reactions to the beta-lactam group, and information on hypersensitivity to each of the other antimicrobial agents is scarce. The present document has been produced by the Special Committee on Drug Allergy of the World Allergy Organization to present the most relevant information on the incidence, clinical manifestations, diagnosis, possible mechanisms, and management of hypersensitivity reactions to non beta-lactam antimicrobials for use by practitioners worldwide.

Antibacterial activity of beta-lactam antibiotics in experimental meningitis due to Streptococcus pneumoniae

In order to define the characteristics of the antibacterial activity of beta-lactam antibiotics in the treatment of bacterial meningitis, the relationship between cerebrospinal fluid (CSF) drug concentrations and the rate of bacterial killing was investigated for penicillin G and four new cephalosporins in an animal model of meningitis due to Streptococcus pneumoniae. All five drugs showed a significant correlation between increasing drug concentrations in CSF and increasing bactericidal rates. Minimal activity was observed in CSF at drug concentrations of approximately the broth minimal bactericidal concentration (MBC). Maximal activity occurred with CSF concentrations 10-30 times higher. In vitro tests did not reproduce the unique correlation of increasing drug concentrations and killing activity found in vivo. When evaluating new beta-lactam antibiotics for the treatment of bacterial meningitis, it is reasonable to establish a minimum standard of CSF drug concentrations of greater than or equal to 30 times the MBC against the infecting organism.

Importance of antibiotic class to the development of Clostridium difficile infection (CDI) in adults: A systematic review

C. difficile causes gastrointestinal infections in humans, including severe diarrhea. It is implicated in 20%-30% of cases of antibiotic-associated diarrhea, in 50%-70% of cases of antibiotic-associated colitis, and in >90% of cases of antibiotic-associated pseudomembranous colitis. Exposure to antimicrobial agent, hospitalization and age are some of the risk factors that predispose to CDI. Virtually all hospitalized patients with nosocomially-acquired CDI have a history of treatment with antimicrobials or neoplastic agent within the previous 2 months. The development of CDI usually occurs during treatment with antibiotics or some weeks after completing the course of the antibiotics. ^ After exposure to the organism (often in a hospital), the median incubation period is less than 1 week, with a median time of onset of 2days. The difference in the time between the use of antibiotic and the development of the disease relate to the timing of exogenous acquisition of C. difficile. ^ This paper reviewed the literature for studies on different classes of antibiotics in association with the rates of primary CDI and RCDI from the year 1984 to 2012. The databases searched in this systematic review were: PubMed (National Library of Medicine) and Medline (R) (Ovid). RefWorks was used to store bibliographic data. ^ The search strategy yielded 733 studies, 692 articles from Ovid Medline (R) and 41 articles from PubMed after removing all duplicates. Only 11 studies were included as high quality studies. Out of the 11 studies reviewed, 6 studies described the development of CDI in non-CDI patients taking antibiotics for other purposes and 5 studies identified the risk factors associated with the development of recurrent CDI after exposure to antibiotics. ^ The risk of developing CDI in non-CDI patients receiving beta lactam antibiotics was 2.35%, while fluoroquinolones, clindamycin/macrolides and other antibiotics were associated with 2.64%, 2.54% and 2.35% respectively. Of those who received beta lactam antibiotic, 26.7% developed RCDI, while 36.8% of those who received any fluoroquinolone developed RCDI, 26.5% of those who received either clindamycin or macrolides developed RCDI and 29.1% of those who received other antibiotics developed RCDI. Continued use of non-C. difficile antibiotics especially fluoroquinolones was identified as an important risk factor for primary CDI and recurrent CDI. ^

Synthesis and evaluation of antibacterial activity of the dual-action agents: beta-lactamase inhibitors with cytotoxic agents or beta-lactam antibiotics

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Screening of Variables Influencing the Clavulanic Acid Production by Streptomyces DAUFPE 3060 Strain

Clavulanic acid (CA) is a beta-lactam antibiotic, which has a potent beta-lactamase inhibiting activity. The influence of five variables, namely pH (6.0, 6.4, and 6.8), temperature (28A degrees C, 30A degrees C, and 32A degrees C), agitation intensity (150, 200, and 250 rpm), glycerol concentration (5.0, 7.5, and 10 g/L) and soybean flour concentration (5.0, 12.5, and 20 g/L), on CA production by a new isolate of Streptomyces (DAUFPE 3060) was investigated in 250-mL Erlenmeyer flasks using a fractional factorial design. Temperature and soybean flour concentration were shown to be the two variables that exerted the most important effects on the production of CA at 95% confidence level. The highest CA concentration (494 mg/L) was obtained after 48 h at 150 rpm, 32A degrees C, pH 6.0, 5.0 g/L glycerol, and 20 g/L soybean flour concentrations. Under these conditions, the yields of biomass and product on consumed substrate were 0.26 g(X)/g(S) and 64.3 mg(P)/g(S), respectively. Fermentations performed in 3.0-L bench-scale fermenter allowed increasing the CA production by about 60%.

Stability of clavulanic acid under variable pH, ionic strength and temperature conditions. A new kinetic approach

Clavulanic acid (CA) is a beta-lactam antibiotic that alone exhibits only weak antibacterial activity, but is a potent inhibitor of beta-lactamases enzymes. For this reason it is used as a therapeutic in conjunction with penicillins and cephalosporins. However, it is a well-known fact that it is unstable not only during its production phase, but also during downstream processing. Therefore, the main objective of this study was the evaluation of CA long-term stability under different conditions of pH and temperature, in the presence of variable levels of different salts, so as to suggest the best conditions to perform its simultaneous production and recovery by two-phase polymer/salt liquid-liquid extractive fermentation. To this purpose, the CA stability was investigated at different values of pH (4.0-8.0) and temperature (20-45 degrees C), and the best conditions were met at a pH 6.0-7.2 and 20 degrees C. Its stability was also investigated at 30 degrees C in the presence of NaCl, Na(2)SO(4), CaCl(2) and MgSO(4) at concentrations of 0.1 and 0.5 M in Mcllvaine buffer (pH 6.5). All salts led to increased CA instability with respect to the buffer alone, and this effect decreased in following sequence: Na(2)SO(4) > MgSO(4) > CaCl(2) > NaCl. Kinetic and thermodynamic parameters of CA degradation were calculated adopting a new model that took into consideration the equilibrium between the active and a reversibly inactivated form of CA after long-time degradation. (C) 2009 Elsevier B.V. All rights reserved.

Fastidious intracellular bacteria as causal agents of community-acquired pneumonia.

Intracellular bacteria are common causes of community-acquired pneumonia that grow poorly or not at all on standard culture media and do not respond to beta-lactam antibiotic therapy. Apart from well-established agents of pneumonia such as Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci and Coxiella burnetii, some new emerging pathogens have recently been recognized, mainly Parachlamydia acanthamoebae and Simkania negevensis, two Chlamydia-related bacteria. Most of them are causes of benign and self-limited infections. However, they may cause severe pneumonia in some cases (i.e., Legionnaires' disease) and they may cause outbreaks representing a public health problem deserving prompt recognition and appropriate therapy. Although extrapulmonary manifestations are often present, no clinical features allow them to be distinguished from classical bacterial agents of pneumonia such as Streptococcus pneumoniae. Thus, specific molecular diagnostic tools are very helpful for early recognition of the offending bacteria, whereas serology often only allows retrospective or late diagnosis. Macrolides remain the best empirical treatment of intracellular respiratory pathogens, although some observational studies suggest that quinolones may be superior for the treatment of legionellosis.

EFEITO DE SURFACTANTES NA ESTABILIDADE DE COMPOSTOS DE USO TERAPEUTICO

A critical revision of literature as regards to the drug stability in the presence of surfactants were realized. The functional groups envolved in the drug decomposition were used to the development of the discussion. The analysis indicated that the detergent effect can be used to control the rates and mechanisms of drug decomposition and to obtain specific information about the drug reactivity in the environment of pharmacological action.

Avaliacao da atividade da nova cefalosporina de quarta geracao cefpiroma contra amostras clinicas isoladas em unidades de terapia intensiva e unidades de oncoematologia de varios hospitais brasileiros

Objective: To evaluate the in vitro activity of the fourth-generation cephalosporin cefpirome in comparison to that of ceftazidime, ceftriaxone, cefotaxime and imipenem in a multicenter study involving nine hospitals from six cities (four states). Material and methods: A total of 804 isolates from patients hospitalized in either intensive care units or Oncology/Hematology units was evaluated. The isolates were collected between June and November of 1995, i.e. before cefpirome became commercially available in Brazil, and susceptibility tested by broth microdilution following the NCCLS procedures. All isolates resistant to cefpirome were retested by B-test. Results: Against Enterobacteriaceae (n = 344), cefpirome demonstrated an activity 2 to 32-fold higher than that of the third-generation cephalosporins (TGCs) and similar to that of imipenem. The percentages of Enterobacteriaceae susceptible were: 88%, 69% and 96% for cefpirome, TGCs and imipenem, respectively, The cefpirome spectrum were greater or equal to that of imipenem against Citrobacter freundii, Enterobacter aerogenes, Morganellao morganii and Serratia marcescens. Against Acinetobacter sp. (n = 77), cefpirome was slightly more active than ceftazidime; however, the percentages of isolates resistant to these compounds were high (84% and 88%, respectively). The activities of cefpirome, ceftazidime and imipenem were very similar against P. aeruginosa isolates (n = 128), with MIC50 (μg/ml) percent susceptible of 8/59%, 8/62% and 4/62% respectively, Against aerobic gram-positive bacteria, the cefpirome activity was 4 to 16-fold higher than that of TGCs but 2 to 8-fold lower than that of imipenem. Conclusion: The results of our study suggest that, in Brazil, cefpirome has a spectrum of activity which is higher than that of the TGCs against aerobic gram-negative (Enterobacteriaceae and non-Enterobacteriaceae) and gram-positive bacteria and similar to that of imipenem against some Enterobacteriaceae species and P. aeruginosa.