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 bla_CMY-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]

Activity of daptomycin, ciprofloxacin, clindamycin and cotrimoxazole against coagulase-negative Staphylococcus strains with diminished susceptibility to vancomycin

M. FAJARDO, R. HIDALGO, S. RODRÍGUEZ, E. GARDUNO, F. F. RODRÍGUEZ, M. ROBLES 

Introduction. Coagulase Negative Staphylococci (CNS) have become one of the most common nosocomial pathogens and it has a high mortality rate due to the increased of seriously ill patients survival, long states immunosuppression and presence of foreign bodies, such as catheters, prostheses, pacemakers, etc. In addition, there is a significant increase in resistance to antimicrobial drugs, especially beta-lactams, and the increase in the MIC for vancomycin leads to a loss of clinical efficacy. This necessitates the search for new therapeutic alternatives, such as daptomycin. The aim of this paper is to study the activity of daptomycin, ciprofloxacin, clindamycin and cotrimoxazole in two groups of clinically significant CNS. a MIC₉₀ with vancomycin ≤ 1 mg/L and the other with MIC₉₀ 2 mg/L.
Methods. We identified and studied MIC₉₀ to ciprofloxacin, clindamycin and cotrimoxazole from 54 strains of clinically significant by the CNS Combo 22 Microscan panels (Dade Behring, Siemens). The MIC₉₀ for daptomycin was performed using Etest (AB BioMérieux, Solna, Sweden) on Mueller Hinton plates (BioMérieux, France).

Results. In Group I (vancomycin MIC₉₀ ≤ 1 mg/L) were 19 strains whereas in Group II (vancomycin MIC₉₀ = 2 mg/L) were 35 strains. Expressed in mg/L, MIC₉₀ ranges for daptomycin were 0.047-0.5 in Group I and 0.064-0.5 in Group II. For ciprofloxacin were 8 sensitive strains and 11 resistant in Group I and 10 sensitive and 25 resistant in Group II. For clindamycin were 7 sensitive strains and 12 resistant in Group I and 16 sensitive and 19 resistant in Group II. Finally, for cotrimoxazole were 10 sensitive strains and 9 resistant in Group I and 19 sensitive and 16 resistant in Group II.
Conclusions. The MIC levels to daptomycin were not influenced by the increase in the MIC for vancomycin. There was no statistically significant difference for the sensitivity of ciprofloxacin between the two groups of vancomycin. Regardless of vancomycin, there were a clear relationship between the sensitivity of ciprofloxacin with clindamycin and cotrimoxazole.

 
Rev Esp Quimioter 2010:23(2):81-86 [pdf]

Methicillin-resistant Staphylococcus aureus: changes in the susceptibility pattern to daptomycin during a 10-year period (2001-2010)  

J. J. PICAZO, C. BETRIU, E. CULEBRAS, I. RODRÍGUEZ-AVIAL, M. GÓMEZ, F. LÓPEZ-FABAL AND VIRA GROUP           

Introduction. The objective of this study was to evaluate the activity of daptomycin and other agents against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from 2001 to 2010, in order to determine changes and to detect resistance trends.
Methods. The study included a total of 1,130 MRSA isolates collected as part of a multicenter surveillance program for antibiotic resistance, Estudio de Vigilancia de Resistencia a los Antimicrobianos (VIRA study), from 51 medical centers throughout Spain between 2001 and 2010. Broth microdilution test was performed according to the Clinical Laboratory Standards Institute guidelines.
Results. Daptomycin showed excellent activity and maintained its activity over time; only one MRSA isolate collected in 2001 was nonsusceptible to this agent (MIC=2 mg/L). Based on the MIC90, daptomycin was 2-4 dilutions more active than vancomycin, teicoplanin and linezolid. Daptomycin retained activity against MRSA isolates that were resistant to linezolid, to quinupristin-dalfopristin, or showed intermediate susceptibility to vancomycin.
Conclusions. Our data and those of other studies, coupled with daptomycin’s rapid bactericidal activity, suggest that this antimicrobial could be an alternative in the treatment of severe infections caused by multiresistant S. aureus.

 
Rev Esp Quimioter 2011:24(2):107-111 [pdf]

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]

Comparative study of the susceptibility to daptomycin and other antimicrobials against Staphylococcus spp. resistant to methicillin and Enterococcus spp. using Wider, E-test, and microdilution methods

J. L. GÓMEZ-GARCÉS, F. LÓPEZ-FABAL, A. BURILLO, Y. GIL 

The human and material costs of inappropriate antimicrobial therapy are high. This study was designed to search for a rapid, simple and effective antimicrobial susceptibility test capable of identifying the best treatment strategy against microorganisms causing hospital infections showing resistance or reduced susceptibility to the more traditional antibiotics. The tests compared were the E-test, an automated test (Wider) and broth microdilution (as the reference test), to determine the susceptibility to vancomycin, teicoplanin, linezolid and daptomycin of clinical isolates of methicillin resistant Staphylococcus aureus (MRSA), methicillin resistant coagulase negative Staphylococcus spp. and Enterococccus spp. The E-test and Wider methods showed good agreement with the reference method indicating their reliability for routine susceptibility testing of staphylococci and enterococci against vancomycin, teicoplanin, linezolid and daptomycin. Notwithstanding, when faced with a serious enterococcal infection, the MIC of daptomycin should be more accurately determined using a reference technique such as broth microdilution.

 
Rev Esp Quimioter 2010:23(2):87-92 [pdf]