Rev Esp Quimioter 2012:25(2):89-99


Emergence of plasmid mediated AmpC β-lactamasas: Origin, importance, detection and therapeutical options 
                 
C. SERAL, M. J GUDE, F. J. CASTILLO                                                            

 
AmpC β-lactamases can hydrolyze penicillins, oxyimino-, 7-α-methoxycephalosporins and monobactams. Susceptibility to cefepime or cefpirome is little affected and is unchanged for carbapenems. Originally such genes are thought to have been mobilized to mobile genetic elements from the chromosomal ampC genes from members of Enterobacteriaceae facilitating their spread and now they can appear in bacterial lacking or poorly expressing a chromosomal ampC gene. The prevalence of infection by plasmid mediated AmpC (pAmpC) varies depending on the type of enzyme and geographical location and blaCMY-2 is the most frequently detected worldwide. Typically, pAmpC producing isolates are associated with resistance to multiple antibiotics making the selection of an effective antibiotic difficult. Phenotypic and molecular methods to detect pAmpC are described and the role of different antibiotics in the treatment of these infections is examined. Surveillance studies about the evolution of this emerging resistant mechanism are important in clinical isolates. Evaluate the in vitro susceptibility of these isolates and the clinical efficacy of other therapeutic options is required.
   

Rev Esp Quimioter 2012:25(2):89-99 [pdf]

/por

Rev Esp Quimioter 2012:25(2):100-121

Antibiotheraphy in the 21st century, antibacterials for the second decade. Posibilities or realities in the future? 
           
J. E. GARCÍA-SÁNCHEZ, E. GARCÍA-MERINO, Á.  MARTÍN-DEL-REY, E. GARCÍA-SÁNCHEZ                                                             

 
A review of some antibacterial products is done motivated by the serious situation arisen by the antimicrobial resistance in bacteria. The attention is focus on those drugs with suitable antimicrobial properties that have prospects to be commercialized in the next years because of they are undergoing a clinical development phase (I, II, III). The search for these antibacterial products has been done by an exhaustive study of conference proceedings and web pages of international congresses on chemotherapy, infectious diseases and new antimicrobial drugs. Some of the new antibacterial products acts on known targets, and they belong to already used families. Furthermore, the great majority acts against the gram-positive bacterium. There is also some limited-spectrum antimicrobial drug whose use would minimize the adverse biological effects.
  

 

Rev Esp Quimioter 2012:25(2):100-121 [pdf]

/por

Rev Esp Quimioter 2012:25(2):122-128

Plasmid-mediated AMPc producing Proteus mirabilis in the Health Care Area of Santiago de Compostela: molecular and epidemiological analysis by rep-PCR and MALDI-TOF 
           

M. TREVIÑO, D. NAVARRO, G. BARBEITO, P. ARESES, C. GARCÍA-RIESTRA, B. J. REGUEIRO                                                               

 
Introduction: Proteus mirabilis is an important pathogen isolated from both community-acquired and health-care associated infections. Acquired AmpC-type beta-lactamases represent an important mechanism of resistance to extended-spectrum cephalosporins and are emerging in several European countries. The objective of this work was to know the prevalence of acquired AmpC beta-lactamase producing P. mirabilis over the last three years and eight months and their clonal relationships comparing MALDI-TOF and automated rep-PCR results.
Methods: P. mirabilis isolates (n= 1,396) were obtained from routine cultures at the University Hospital Complex of Santiago de Compostela from January 2006 to August 2009. Identification to the species level and antimicrobial susceptibility testing were achieved with Vitek 2. The isolates showing intermediate or total resistance to amoxicillin-clavulanic and cefoxitin, cefotaxime or ceftazidime were selected for AmpC phenotypic detection by double-disk synergy test, and molecular confirmation by multiplex PCR. Molecular typing of the isolates was performed by automated rep-PCR and MALDI-TOF.
Results: For the last three years and eight months, the prevalence of AmpC-producing P. mirabilis increased from 0.17% to 4.5%, mainly associated with urinary tract infection in elderly outpatients. In all cases, plasmidic AmpC belonging to LAT/CMY lineage were detected. A high genetic variability was seen with both, rep-PCR and MALDI-TOF MS.
Conclusions: AmpC-producing P. mirabilis is an emergent pathogen. The high genetic variability detected suggests that the spread of the resistance mechanism is more probable than a clone dispersion. Automated rep-PCR and MALDI-TOF MS show as fast and decisive methods for bacterial strain typing in clinical microbiology laboratories.
  

 

Rev Esp Quimioter 2012:25(2):122-128 [pdf]

/por

Rev Esp Quimioter 2012:25(2):129-133

Peripheral venous catheter-related bacteremia in a general hospital     

M. DELGADO-CAPEL, A. GABILLO, L. ELIAS, J. C. YÉBENES, G. SAUCA, J. A. CAPDEVILA                                                               

 
Introduction. Catheter sepsis is a constant and serious problem in our hospitals for the cost it generates, both in terms of morbidity and economics. It’s becoming more frequent also in peripherally inserted catheters. Our study aims to know the importance and characteristics of peripheral venous catheter bacteremia in a general hospital.
Material and methods. Prospective and comparative analysis of all episodes of central and peripheral venous catheter-related bacteraemia, in 2009.
Results. Twenty-eight episodes of catheter-related bacteraemia in a total of 25 patients. Sixteen episodes originated in central catheter (57.2%), 11 in peripheral (39.3%) and 1 in peripherally inserted central catheter (3.5%). Two cases of exitus directly related to the peripheral catheter infection. Etiology: 13 episodes of S. aureus (3 MRSA), including 8 in peripheral catheter (8/13, 61.5%), 12 episodes of plasma coagulase negative staphylococcus, including 2 in peripheral catheter (2/12, 16.6%).
Conclusions. Peripheral catheter-related bacteraemia is an emerging health problem with important clinical and prognostic connotations for patients. It is necessary continuous training on correct handling measures to prevent intravascular catheters infections including peripheral catheters in every hospital ward. 

 

Rev Esp Quimioter 2012:25(2):129-133 [pdf]

/por

Rev Esp Quimioter 2012:25(2):134-138

Rifampin breakpoint for Acinetobacter baumannii based on pharmacokinetic-pharmacodynamic models with Monte Carlo simulation     

J. A LEPE, E. GARCÍA-CABRERA, M.V. GIL-NAVARRO, J. AZNAR                                                                

 
Objective: The aim of this study is to develop a pharmacokinetic–pharmacodynamic (PK–PD) rifampin breakpoint for Acinetobacter baumannii based on Monte Carlo simulation and to compare it with the reference value establish by the French Society for Microbiology (SFM).
Methods: A 10,000 subject’s Monte Carlo simulation for rifampin with intravenous dose of 10 mg/Kg/day and 20 mg/Kg/day was performed. The distribution of MIC was calculated using unique clinical isolates of A. baumannii. The PK–PD parameter calculated was Cmaxfree/MIC.
Results: The isolates rifampin MIC50 and MIC90 were 2 and 32 mg/L respectively, ranging between 0.023-32 mg/L. According to interpretive criteria established by the SFM: 468 (75.8%) isolates were susceptible (MIC ≤ 4 mg/L) and 150 (24.2%) were non susceptible (MIC > 4 mg/L).
For 10 mg/Kg/day dose: the probability (%) of attaining Cmaxfree/ MIC ratio values = 8 by Monte Carlo simulation in the study population was 0.4%, the rifampin MIC cut off value obtained from an optimal treatment (target ≥ 90%), was 0.125 mg/L. The probability of obtaining a Cmaxfree/MIC ratio equal to 10 was 0.2% and the MIC cut off value obtained <0.125 mg/L.
At doses of 20 mg/kg/day: the probability of obtaining a Cmaxfree/MIC ratio equal to 8 was 0.8%, the rifampin MIC cut off value obtained was 0.25 mg/L. For a Cmaxfree/MIC = 10, it was 0.6% and 0.125 mg/L, respectively. The percentage of susceptible isolates ranging 0% to 1%, depending on the dose and therapeutic target used.
Conclusion: the rifampin breakpoints obtained from our PK/PD Monte Carlo simulation differ from those established by SFM, although further clinical studies in patients are needed to confirm our findings and improve the use of this antibiotic. 

 

Rev Esp Quimioter 2012:25(2):134-138 [pdf]

/por

Rev Esp Quimioter 2012:25(2):139-146

Antibiotic prescribing to the paediatric population of Castilla y León in the last decade: trends, seasonal fluctuations and geographical differences            

M. E. VÁZQUEZ, J. M. EIROS, F. MARTÍN, S. GARCÍA, R. M. BACHILLER, M. J. VÁZQUEZ                                                                   

 
Introduction. The development of antibiotic resistance is a danger to the health of the population, especially for children, due to low antimicrobial arsenal available to them.
Material and methods. We performed a retrospective observational study referred to the prescriptions of systemic antibiotic in the paediatric population of Castilla y León in the years 2001 to 2010.
Results. The total use of antibiotics outside hospitals is around to 20.7 DID (defined daily dose per 1,000 inhabitants per day). There are two different phases: the first from 2001 to 2007 where there is an increase of consumption, with a peak of 25 DID in 2003, following a phase of decline, with a minimum of 18 DID in 2010. Broad-spectrum penicillins are the most used. We also observe changes in prescription trends. It has a clear seasonal prescription profile related to acute respiratory infections (ARI) of winter, stands in February. The use of antibiotics varies substantially between different Health Areas.
Conclusions. We observed a decrease in antibiotic prescription to children in the last three years. Changes in the prescription profile for amoxicillin and at the expense of greater spectrum antibacterial antibiotics indicate a better match to therapeutic guidelines in recent years. The variability found in different Health Areas suggests the need for improvement in the rational use of antibiotic, at least to some.
 

Rev Esp Quimioter 2012:25(2):139-146 [pdf]

/por

Rev Esp Quimioter 2012:25(2):147-154

Prospective comparison of severity scores for predicting mortality in community-acquired pneumonia              

S. LUQUE, J. GEA, P. SABALLS, O. FERRÁNDEZ, N. BERENGUER, S. GRAU                                                                      

 
Introduction. Specific prognostic models for communityacquired pneumonia (CAP) to guide treatment decisions have been developed, such us the Pneumonia Severity Index (PSI) and the Confusion, Urea nitrogen, Respiratory rate, Blood pressure and age ≥ 65 years index (CURB-65). Additionally, general models are available such as the Mortality Probability Model (MPM-II). So far, which score performs better in CAP remains controversial. The objective was to compare PSI and CURB-65 and the general model, MPM-II, for predicting 30-day mortality in patients admitted with CAP.
Methods. Prospective observational study including all consecutive patients hospitalised with a confirmed diagnosis of CAP and treated according to the hospital guidelines. Comparison of the overall discriminatory power of the models was performed by calculating the area under a receiver operator characteristic curve (AUC ROC curve) and calibration through the Goodness-of-fit test.
Results. One hundred and fifty two patients were included (mean age 73.0 years; 69.1% male; 75.0% with more than one comorbid condition). Seventy-five percent of the patients were classified as high-risk subjects according to the PSI, versus 61.2% according to the CURB-65. The 30-day mortality rate was 11.8%. All three scores obtained acceptable and similar values of the AUCs of the ROC curve for predicting mortality. Despite all rules showed good calibration, this seemed to be better for CURB-65. CURB-65 also revealed the highest positive likelihood ratio.
Conclusions. CURB-65 performs similar to PSI or MPMII for predicting 30-day mortality in patients with CAP. Consequently, this simple model can be regarded as a valid alternative to the more complex rules.

 

Rev Esp Quimioter 2012:25(2):147-154 [pdf]

/por