Josep M. Sierra - Academia.edu (original) (raw)

Papers by Josep M. Sierra

Research paper thumbnail of Adherence of S. epidermidis on different metals. A comparative in vitro study

Journal of Applied Biomaterials & Functional Materials, 2014

Staphylococcus epidermidis is the most common cause of orthopedic infections. Adhesion and biofil... more Staphylococcus epidermidis is the most common cause of orthopedic infections. Adhesion and biofilm formation on orthopedic implant surfaces play an important role in the physiopathology of these infections. The aim of our study was to evaluate the adhesion of S. epidermidis on the surface of metals usually used in orthopedics. Previously sterilized circular metal plates of titanium (Ti), porous titanium (p-Ti), cobalt chromium (CoCr) and stainless steel (SS) were hung completely submerged in a liquid medium with a known concentration of S. epidermidis (RP62A). They were incubated for 1 h or 24 h at 36°C. After incubation, each plate was washed with PBS and sonicated during 5 minutes in 10 mL of saline. Different dilutions were performed and 100 µL from each sample was cultured on agar plates. 26 metal plates were incubated for 1 h and other 55 metal plates for 24 h. The lowest bacterial count (cfu/mm2) at 1 h was observed in CoCr plates while in p-Ti it was 6 times higher. At 24 h the highest bacterial count was observed in SS plates while the lowest in Ti. However, these differences were not statistically significant. After 1 h and 24 h of exposure, the lowest adherence was observed in CoCr and Ti plates, respectively. However, bacterial attachment occurred with all materials. It is necessary to further investigate new materials able to avoid bacterial attachment.

Research paper thumbnail of A Role for Human SPα as a Pattern Recognition Receptor

Journal of Biological Chemistry, Oct 20, 2005

Human Sp␣ is a soluble protein belonging to group B of the scavenger receptor cysteine-rich (SRCR... more Human Sp␣ is a soluble protein belonging to group B of the scavenger receptor cysteine-rich (SRCR) superfamily for which little functional information is available. It is expressed by macrophages present in lymphoid tissues (spleen, lymph node, thymus, and bone marrow), and it binds to myelomonocytic and lymphoid cells, which suggests that it may play an important role in the regulation of the innate and adaptive immune systems.

Research paper thumbnail of Prevalence of two different genes encoding NorA in 23 clinical strains of Staphylococcus aureus

Journal of Antimicrobial Chemotherapy

Research paper thumbnail of ComplutenseUniversityofMadrid,Madrid28040,Spain

Research paper thumbnail of In Vitro Acinetobacter baumannii Colistin Resistant Mutants Show an Increased LPS Production and Outer Membrane Protein Modification

Background: Acinetobacter baumannii is an opportunistic pathogen causing infections mainly in pat... more Background: Acinetobacter baumannii is an opportunistic pathogen causing infections mainly in patients in intensive care units, where the extensive use of antimicrobial agents can select for the emergence of multidrug resistant strains. Colistin remains as the last solution to treat infections caused by these multiresistant clinical isolates. The objective of this work was to determine the mechanisms of resistance to colistin in an A.baumannii clinical isolate. Methods: A. baumannii clinical isolate 77778 was subjected to increased colistin concentrations. The final mutant strain was able to grow in media with 256 mg/L of colistin and was stable to passages in non-selective media. LPS were obtained after proteinase K digestion of whole cells and were separated by SDS-PAGE. Cultures were grown in presence and absence of different amounts of colistin. Cell envelope protein extracts were also analysed by SDS-PAGE electrophoresis to study changes in protein expression. Results: The LPS ...

Research paper thumbnail of Prevalence and Molecular Characterization of Methicillin-Resistant Staphylococcus aureus ST398 Resistant to Tetracycline at a Spanish Hospital over 12 Years

PLoS ONE, 2013

Methicillin-resistant Staphylococcus aureus (MRSA) ST398, associated with livestock animals, was ... more Methicillin-resistant Staphylococcus aureus (MRSA) ST398, associated with livestock animals, was described in 2003 as a new lineage infecting or colonizing humans. We evaluated the prevalence and molecular characteristics of MRSA ST398 isolated in the Hospital Universitari de Bellvitge from January 2000 to June 2011. Tetracycline resistant (Tet-R) MRSA isolates from single patients (pts) were screened by SmaI-pulsed field gel electrophoresis (PFGE). Nontypable MRSA strains by SmaI (NT Sma I)-MRSA were further analysed by ApaI-PFGE, spa, SCCmec, agr, MLST typing, and by DNA microarray hybridization. Among 164 pts harboring Tet-R MRSA, NT Sma I-MRSA ST398-agrI was found in 33 pts (20%). Although the first pt was detected in 2003, 22/33 pts (67%) were registered in the 2010-2011 period. Ten pts (30%) were infected and cancer was the most frequent underlying disease. In one case, death was due to MRSA-ST398-related infection. Five pulsotypes (A-E) were detected using ApaI-PFGE, with type A accounting for 76% of the strains. The majority of the studied isolates presented spa type t011 (70%) and SCCmec type V (88%). One strain was spa negative both by PCR and microarray analysis. Forty-nine percent of the studied isolates showed resistance to 3 or more antibiotic classes, in addition to beta-lactams. Ciprofloxacin resistance was 67%. Tet-R was mediated by tet(M) and tet(K) in 26 isolates. All isolates lacked Panton-Valentine Leukocidin production, as well as other significant toxins. This study displays the molecular features of MRSA-ST398 clone and shows the increase in tetracycline resistance together with arise in MRSA-ST398 isolates infecting or colonizing patients in our clinical setting.

Research paper thumbnail of Analysis of the clonal relationship among clinical isolates of Salmonella enterica serovar Infantis by different typing methods

Revista do Instituto de Medicina Tropical de São Paulo, 2003

Salmonella Infantis has been the second most common serovar in Argentina in the last two years, b... more Salmonella Infantis has been the second most common serovar in Argentina in the last two years, being isolated mostly from paediatric hospitalised patients. In order to determine the clonal relationship among Salmonella Infantis strains, we examined 15 isolates from paediatric patient faeces in Argentina (12 geographically related and 3 geographically non-related) by using antimicrobial susceptibility, plasmid profiling, repetitive extragenic palindromic (REP) PCR, enterobacterial repetitive intergenic consensus (ERIC) PCR, and low-frequency restriction analysis of chromosomal DNA by pulsed field gel electrophoresis (PFGE). Four Spanish strains were included as controls of clonal diversity in molecular techniques. Antibiotype and plasmid profile was not useful as epidemiological tools. PFGE and REP-PCR were able to discriminate between Argentinean and Spanish isolates of Salmonella Infantis allowing to detect genetically related strains in three different cities. This finding indicates that a possible spread of a clone of this serovar in the North-eastern Region of Argentina has taken place in 1998. MERINO, L.A.; RONCONI, M.C.; NAVIA, M.M.; RUIZ, J.; SIERRA, J.M.; CECH, N.B.; LODEIRO, N.S. & VILA, J. -Analysis of the clonal relationship among clinical isolates of Salmonella enterica serovar Infantis by different typing methods. Rev. Inst. Med. trop. S. Paulo, 45(3):119-123, 2003.

Research paper thumbnail of Tratamiento de la infección aguda de la artroplastia total o parcial de cadera con desbridamiento y régimen antibiótico oral

Medicina Clínica, 2003

Información del artículo Tratamiento de la infección aguda de la artroplastia total o parcial de ... more Información del artículo Tratamiento de la infección aguda de la artroplastia total o parcial de cadera con desbridamiento y régimen antibiótico oral.

Research paper thumbnail of Bacterial Load And Biofilm Thickness Of Endotracheal Tubes From Ventilated Piglets With MRSA Pneumonia And Antimicrobial Treatment

B52. VENTILATOR ASSOCIATED AND NOSOCOMIAL PNEUMONIA, 2010

Research paper thumbnail of Low Prevalence of Cfr-Mediated Linezolid Resistance among Methicillin-Resistant Staphylococcus aureus in a Spanish Hospital: Case Report on Linezolid Resistance Acquired during Linezolid Therapy

PLoS ONE, 2013

Linezolid is an effective antimicrobial agent to treat methicillin-resistant Staphylococcus aureu... more Linezolid is an effective antimicrobial agent to treat methicillin-resistant Staphylococcus aureus (MRSA). Resistance to linezolid due to the cfr gene is described worldwide. The present study aimed to analyze the prevalence of the cfr-mediated linezolid resistance among MRSA clinical isolates in our area. A very low prevalence of cfr mediated linezolid resistance was found: only one bacteremic isolate out of 2 215 screened isolates. The only linezolid resistant isolate arose in a patient, previously colonized by MRSA, following linezolid therapy. Despite the low rate of resistance in our area, ongoing surveillance is advisable to avoid the spread of linezolid resistance. Citation: Sierra JM, Camoez M, Tubau F, Gasch O, Pujol M, et al. (2013) Low Prevalence of Cfr-Mediated Linezolid Resistance among Methicillin-Resistant Staphylococcus aureus in a Spanish Hospital: Case Report on Linezolid Resistance Acquired during Linezolid Therapy. PLoS ONE 8(3): e59215.

Research paper thumbnail of A Role for Human SP  as a Pattern Recognition Receptor

Journal of Biological Chemistry, 2005

Human Sp␣ is a soluble protein belonging to group B of the scavenger receptor cysteine-rich (SRCR... more Human Sp␣ is a soluble protein belonging to group B of the scavenger receptor cysteine-rich (SRCR) superfamily for which little functional information is available. It is expressed by macrophages present in lymphoid tissues (spleen, lymph node, thymus, and bone marrow), and it binds to myelomonocytic and lymphoid cells, which suggests that it may play an important role in the regulation of the innate and adaptive immune systems.

Research paper thumbnail of Mechanisms of resistance to ampicillin, chloramphenicol and quinolones in multiresistant Salmonella typhimurium strains isolated from fish

Journal of Antimicrobial Chemotherapy, 1999

Research paper thumbnail of Prevalence of two different genes encoding NorA in 23 clinical strains of Staphylococcus aureus

Journal of Antimicrobial Chemotherapy, 2000

Research paper thumbnail of In vitro activity of rifaximin against bacterial enteropathogens causing diarrhoea in children under 5 years of age in Ifakara, Tanzania

Journal of Antimicrobial Chemotherapy, 2001

Research paper thumbnail of Antibacterial evaluation of a collection of norfloxacin and ciprofloxacin derivatives against multiresistant bacteria

International Journal of Antimicrobial Agents, 2006

The objective of this study was to analyse an array of ciprofloxacin and norfloxacin derivatives ... more The objective of this study was to analyse an array of ciprofloxacin and norfloxacin derivatives in order to determine those with good activity against bacteria that already present fluoroquinolone resistance associated with mutations in the gyrA and/or parC genes. Four norfloxacin and 20 ciprofloxacin derivatives were synthesised and tested against quinolone-susceptible and -resistant Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus strains using a microdilution test. Among the derivatives, the 4methyl-7-piperazine ciprofloxacin derivative showed a minimum inhibitory concentration for 50% of the organisms that was 16-and 8-fold lower than ciprofloxacin for A. baumannii and S. maltophilia, respectively. When the methyl group at position 4 in the piperazine ring was substituted by ethyl, butyl or heptyl groups, activity against A. baumannii steadily decreased. The 7-(4-methyl)-piperazine ciprofloxacin derivative (UB-8902) showed very good activity against these multiresistant microorganisms including A. baumannii and S. maltophilia.

Research paper thumbnail of In vitro activity of gemifloxacin against clinical isolates of Neisseria gonorrhoeae with and without mutations in the gyrA gene

International Journal of Antimicrobial Agents, 2003

The MIC of gemifloxacin and five other quinolones was tested against 31 clinical isolates of Neis... more The MIC of gemifloxacin and five other quinolones was tested against 31 clinical isolates of Neisseria gonorrhoeae ; strains were analyzed for the presence of mutations in both the gyr A and par C genes. Only seven strains were resistant to nalidixic acid due to a mutation in the gyr A gene but not in the par C gene, with six and two considered intermediate to ciprofloxacin and levofloxacin, respectively. The activity of gemifloxacin was similar to that of trovafloxacin and moxifloxacin, but was more active than nalidixic acid, ciprofloxacin or levofloxacin against the gyr A mutant strains. Gemifloxacin is a valid therapeutic alternative to treat infections with N. gonorrhoeae , retaining its activity against strains already presenting a mutation in gyr A. #

Research paper thumbnail of P881 Altered outer membrane protein profiles of Pseudomonas aeruginosa highly susceptible to the effiux pump inhibitor Phe-Arg-β-naphthylamide

International Journal of Antimicrobial Agents, 2007

Both the PAO1deltamutS and the wild-type PAO1 P. aeruginosa strains (5×109−1×1010 cfu/mL) were ex... more Both the PAO1deltamutS and the wild-type PAO1 P. aeruginosa strains (5×109−1×1010 cfu/mL) were exposed to agar plates containing different antibiotic concentrations (range 0.25-256 mg/L) of tobramycin (TOB), ceftazidime (CAZ), imipenem (IMP), ciprofloxacin (CIP), and levofloxacin (LEV). Sixty five mutants recovered from plates immediately below the mutant prevention concentration were selected and susceptibility (standard CLSI agar dilution) to different antibiotics was determined. Topoisomerase (II and IV) mutations, expression of efflux pumps (MexAB-OprM, MexCD-OprJ, and MexXY) and AmpC b-lactamase, and OprD deficiency were analyzed in selected mutants. Results: The original PAO1deltamutS strain was less susceptible than its parental wild-type PAO1 strain for CAZ (8 and 1 mg/L, respectively) and TOB (2 and 0.5 mg/L). Mutants derived form the PAO1deltamutS strain were obtained in plates with higher CAZ, IMP, or TOB antibiotic concentrations (1−2 log dilutions) than those permitting the growth of mutants originated in normo-mutable PAO1 strain. Indeed mutants obtained from PAO1deltamutS strain were regularly less susceptible (1−4 log dilutions) than those selected form the wild-type PAO1 strain. Mutants selected on CAZ and IMP have reduced susceptibility restricted to b-lactam antibiotics. In these mutants, the MICs and enzymatic activity were compatible with a higher production of chromosomal AmpC enzyme in the case of CAZ selected mutants, whereas AmpC hyper-production superimposed with OprD reduction was observed in the case of IMP. In mutants selected with CIP or LEV, overproduction of efflux pumps was mainly observed with PAO1 strain and overproduction of pumps superimposed with gyrA mutations with PAO1deltamutS strain. Conclusions: The higher antibiotic resistance levels of mutants derived from dense populations of PAO1deltamutS P. aeruginosa when compared with those from the corresponding normo-mutable PAO1 wild-type strain might result from the selection of cells carrying double mutations. Hyper-mutable strains contribute to the single-step selection of variants with higher levels of antibiotic resistance.

Research paper thumbnail of P879 Cloning of a mdfA-like gene, encoding an effiux pump of an Acinetobacter baumannii clinical isolate

International Journal of Antimicrobial Agents, 2007

association of the different amino acid substitutions with resistance patterns to other fluoroqui... more association of the different amino acid substitutions with resistance patterns to other fluoroquinolones.

Research paper thumbnail of Characterization of sparfloxacin-resistant mutants of Staphylococcus aureus obtained in vitro

International Journal of Antimicrobial Agents, 2001

A sparfloxacin-susceptible clinical isolate of Staphylococcus aureus was grown in increased conce... more A sparfloxacin-susceptible clinical isolate of Staphylococcus aureus was grown in increased concentrations of sparfoxacin. The presence of mutations in gyrA, gyrB, grlA and grlB genes was analyzed. The primary point mutation was located in the gyrA gene (Glu-88 to Lys). Two further mutation steps appeared in the amino acid change Ser-80 to Tyr in GrlA. No mutations occurred in the gyrB or grlB genes. Efflux pumps involved in the increase of resistance were also found to affect norfloxacin and ciprofloxacin. This effect may be related to NorA. An overexpression of NorA, may be associated with the increase of the MIC of norfloxacin from 32 mg/l to \200 mg/l in the final mutant. The MICs levels of sparfloxacin were affected by unknown mechanism.

Research paper thumbnail of Antibiotic resistance in orthopaedic surgery: acute knee prosthetic joint infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae

European Journal of Clinical Microbiology & Infectious Diseases, 2010

The aim of this study was to describe the prevalence and characteristics of knee prosthetic joint... more The aim of this study was to describe the prevalence and characteristics of knee prosthetic joint infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. From 2000 to 2007, 132 infections out of 5,076 arthroplasties (2.6%) were registered. Seven out of 132 infections (5.3%) were due to ESBL-producing Enterobacteriaceae, Escherichia coli in six cases and Klebsiella pneumoniae in one. Open debridement and retention of the implant was the first surgical approach and all patients received intravenous carbapenems. Relapse was documented in four cases and remission in three. Therefore, debridement without prosthesis removal was associated with a high failure rate.

Research paper thumbnail of Adherence of S. epidermidis on different metals. A comparative in vitro study

Journal of Applied Biomaterials & Functional Materials, 2014

Staphylococcus epidermidis is the most common cause of orthopedic infections. Adhesion and biofil... more Staphylococcus epidermidis is the most common cause of orthopedic infections. Adhesion and biofilm formation on orthopedic implant surfaces play an important role in the physiopathology of these infections. The aim of our study was to evaluate the adhesion of S. epidermidis on the surface of metals usually used in orthopedics. Previously sterilized circular metal plates of titanium (Ti), porous titanium (p-Ti), cobalt chromium (CoCr) and stainless steel (SS) were hung completely submerged in a liquid medium with a known concentration of S. epidermidis (RP62A). They were incubated for 1 h or 24 h at 36°C. After incubation, each plate was washed with PBS and sonicated during 5 minutes in 10 mL of saline. Different dilutions were performed and 100 µL from each sample was cultured on agar plates. 26 metal plates were incubated for 1 h and other 55 metal plates for 24 h. The lowest bacterial count (cfu/mm2) at 1 h was observed in CoCr plates while in p-Ti it was 6 times higher. At 24 h the highest bacterial count was observed in SS plates while the lowest in Ti. However, these differences were not statistically significant. After 1 h and 24 h of exposure, the lowest adherence was observed in CoCr and Ti plates, respectively. However, bacterial attachment occurred with all materials. It is necessary to further investigate new materials able to avoid bacterial attachment.

Research paper thumbnail of A Role for Human SPα as a Pattern Recognition Receptor

Journal of Biological Chemistry, Oct 20, 2005

Human Sp␣ is a soluble protein belonging to group B of the scavenger receptor cysteine-rich (SRCR... more Human Sp␣ is a soluble protein belonging to group B of the scavenger receptor cysteine-rich (SRCR) superfamily for which little functional information is available. It is expressed by macrophages present in lymphoid tissues (spleen, lymph node, thymus, and bone marrow), and it binds to myelomonocytic and lymphoid cells, which suggests that it may play an important role in the regulation of the innate and adaptive immune systems.

Research paper thumbnail of Prevalence of two different genes encoding NorA in 23 clinical strains of Staphylococcus aureus

Journal of Antimicrobial Chemotherapy

Research paper thumbnail of ComplutenseUniversityofMadrid,Madrid28040,Spain

Research paper thumbnail of In Vitro Acinetobacter baumannii Colistin Resistant Mutants Show an Increased LPS Production and Outer Membrane Protein Modification

Background: Acinetobacter baumannii is an opportunistic pathogen causing infections mainly in pat... more Background: Acinetobacter baumannii is an opportunistic pathogen causing infections mainly in patients in intensive care units, where the extensive use of antimicrobial agents can select for the emergence of multidrug resistant strains. Colistin remains as the last solution to treat infections caused by these multiresistant clinical isolates. The objective of this work was to determine the mechanisms of resistance to colistin in an A.baumannii clinical isolate. Methods: A. baumannii clinical isolate 77778 was subjected to increased colistin concentrations. The final mutant strain was able to grow in media with 256 mg/L of colistin and was stable to passages in non-selective media. LPS were obtained after proteinase K digestion of whole cells and were separated by SDS-PAGE. Cultures were grown in presence and absence of different amounts of colistin. Cell envelope protein extracts were also analysed by SDS-PAGE electrophoresis to study changes in protein expression. Results: The LPS ...

Research paper thumbnail of Prevalence and Molecular Characterization of Methicillin-Resistant Staphylococcus aureus ST398 Resistant to Tetracycline at a Spanish Hospital over 12 Years

PLoS ONE, 2013

Methicillin-resistant Staphylococcus aureus (MRSA) ST398, associated with livestock animals, was ... more Methicillin-resistant Staphylococcus aureus (MRSA) ST398, associated with livestock animals, was described in 2003 as a new lineage infecting or colonizing humans. We evaluated the prevalence and molecular characteristics of MRSA ST398 isolated in the Hospital Universitari de Bellvitge from January 2000 to June 2011. Tetracycline resistant (Tet-R) MRSA isolates from single patients (pts) were screened by SmaI-pulsed field gel electrophoresis (PFGE). Nontypable MRSA strains by SmaI (NT Sma I)-MRSA were further analysed by ApaI-PFGE, spa, SCCmec, agr, MLST typing, and by DNA microarray hybridization. Among 164 pts harboring Tet-R MRSA, NT Sma I-MRSA ST398-agrI was found in 33 pts (20%). Although the first pt was detected in 2003, 22/33 pts (67%) were registered in the 2010-2011 period. Ten pts (30%) were infected and cancer was the most frequent underlying disease. In one case, death was due to MRSA-ST398-related infection. Five pulsotypes (A-E) were detected using ApaI-PFGE, with type A accounting for 76% of the strains. The majority of the studied isolates presented spa type t011 (70%) and SCCmec type V (88%). One strain was spa negative both by PCR and microarray analysis. Forty-nine percent of the studied isolates showed resistance to 3 or more antibiotic classes, in addition to beta-lactams. Ciprofloxacin resistance was 67%. Tet-R was mediated by tet(M) and tet(K) in 26 isolates. All isolates lacked Panton-Valentine Leukocidin production, as well as other significant toxins. This study displays the molecular features of MRSA-ST398 clone and shows the increase in tetracycline resistance together with arise in MRSA-ST398 isolates infecting or colonizing patients in our clinical setting.

Research paper thumbnail of Analysis of the clonal relationship among clinical isolates of Salmonella enterica serovar Infantis by different typing methods

Revista do Instituto de Medicina Tropical de São Paulo, 2003

Salmonella Infantis has been the second most common serovar in Argentina in the last two years, b... more Salmonella Infantis has been the second most common serovar in Argentina in the last two years, being isolated mostly from paediatric hospitalised patients. In order to determine the clonal relationship among Salmonella Infantis strains, we examined 15 isolates from paediatric patient faeces in Argentina (12 geographically related and 3 geographically non-related) by using antimicrobial susceptibility, plasmid profiling, repetitive extragenic palindromic (REP) PCR, enterobacterial repetitive intergenic consensus (ERIC) PCR, and low-frequency restriction analysis of chromosomal DNA by pulsed field gel electrophoresis (PFGE). Four Spanish strains were included as controls of clonal diversity in molecular techniques. Antibiotype and plasmid profile was not useful as epidemiological tools. PFGE and REP-PCR were able to discriminate between Argentinean and Spanish isolates of Salmonella Infantis allowing to detect genetically related strains in three different cities. This finding indicates that a possible spread of a clone of this serovar in the North-eastern Region of Argentina has taken place in 1998. MERINO, L.A.; RONCONI, M.C.; NAVIA, M.M.; RUIZ, J.; SIERRA, J.M.; CECH, N.B.; LODEIRO, N.S. & VILA, J. -Analysis of the clonal relationship among clinical isolates of Salmonella enterica serovar Infantis by different typing methods. Rev. Inst. Med. trop. S. Paulo, 45(3):119-123, 2003.

Research paper thumbnail of Tratamiento de la infección aguda de la artroplastia total o parcial de cadera con desbridamiento y régimen antibiótico oral

Medicina Clínica, 2003

Información del artículo Tratamiento de la infección aguda de la artroplastia total o parcial de ... more Información del artículo Tratamiento de la infección aguda de la artroplastia total o parcial de cadera con desbridamiento y régimen antibiótico oral.

Research paper thumbnail of Bacterial Load And Biofilm Thickness Of Endotracheal Tubes From Ventilated Piglets With MRSA Pneumonia And Antimicrobial Treatment

B52. VENTILATOR ASSOCIATED AND NOSOCOMIAL PNEUMONIA, 2010

Research paper thumbnail of Low Prevalence of Cfr-Mediated Linezolid Resistance among Methicillin-Resistant Staphylococcus aureus in a Spanish Hospital: Case Report on Linezolid Resistance Acquired during Linezolid Therapy

PLoS ONE, 2013

Linezolid is an effective antimicrobial agent to treat methicillin-resistant Staphylococcus aureu... more Linezolid is an effective antimicrobial agent to treat methicillin-resistant Staphylococcus aureus (MRSA). Resistance to linezolid due to the cfr gene is described worldwide. The present study aimed to analyze the prevalence of the cfr-mediated linezolid resistance among MRSA clinical isolates in our area. A very low prevalence of cfr mediated linezolid resistance was found: only one bacteremic isolate out of 2 215 screened isolates. The only linezolid resistant isolate arose in a patient, previously colonized by MRSA, following linezolid therapy. Despite the low rate of resistance in our area, ongoing surveillance is advisable to avoid the spread of linezolid resistance. Citation: Sierra JM, Camoez M, Tubau F, Gasch O, Pujol M, et al. (2013) Low Prevalence of Cfr-Mediated Linezolid Resistance among Methicillin-Resistant Staphylococcus aureus in a Spanish Hospital: Case Report on Linezolid Resistance Acquired during Linezolid Therapy. PLoS ONE 8(3): e59215.

Research paper thumbnail of A Role for Human SP  as a Pattern Recognition Receptor

Journal of Biological Chemistry, 2005

Human Sp␣ is a soluble protein belonging to group B of the scavenger receptor cysteine-rich (SRCR... more Human Sp␣ is a soluble protein belonging to group B of the scavenger receptor cysteine-rich (SRCR) superfamily for which little functional information is available. It is expressed by macrophages present in lymphoid tissues (spleen, lymph node, thymus, and bone marrow), and it binds to myelomonocytic and lymphoid cells, which suggests that it may play an important role in the regulation of the innate and adaptive immune systems.

Research paper thumbnail of Mechanisms of resistance to ampicillin, chloramphenicol and quinolones in multiresistant Salmonella typhimurium strains isolated from fish

Journal of Antimicrobial Chemotherapy, 1999

Research paper thumbnail of Prevalence of two different genes encoding NorA in 23 clinical strains of Staphylococcus aureus

Journal of Antimicrobial Chemotherapy, 2000

Research paper thumbnail of In vitro activity of rifaximin against bacterial enteropathogens causing diarrhoea in children under 5 years of age in Ifakara, Tanzania

Journal of Antimicrobial Chemotherapy, 2001

Research paper thumbnail of Antibacterial evaluation of a collection of norfloxacin and ciprofloxacin derivatives against multiresistant bacteria

International Journal of Antimicrobial Agents, 2006

The objective of this study was to analyse an array of ciprofloxacin and norfloxacin derivatives ... more The objective of this study was to analyse an array of ciprofloxacin and norfloxacin derivatives in order to determine those with good activity against bacteria that already present fluoroquinolone resistance associated with mutations in the gyrA and/or parC genes. Four norfloxacin and 20 ciprofloxacin derivatives were synthesised and tested against quinolone-susceptible and -resistant Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus strains using a microdilution test. Among the derivatives, the 4methyl-7-piperazine ciprofloxacin derivative showed a minimum inhibitory concentration for 50% of the organisms that was 16-and 8-fold lower than ciprofloxacin for A. baumannii and S. maltophilia, respectively. When the methyl group at position 4 in the piperazine ring was substituted by ethyl, butyl or heptyl groups, activity against A. baumannii steadily decreased. The 7-(4-methyl)-piperazine ciprofloxacin derivative (UB-8902) showed very good activity against these multiresistant microorganisms including A. baumannii and S. maltophilia.

Research paper thumbnail of In vitro activity of gemifloxacin against clinical isolates of Neisseria gonorrhoeae with and without mutations in the gyrA gene

International Journal of Antimicrobial Agents, 2003

The MIC of gemifloxacin and five other quinolones was tested against 31 clinical isolates of Neis... more The MIC of gemifloxacin and five other quinolones was tested against 31 clinical isolates of Neisseria gonorrhoeae ; strains were analyzed for the presence of mutations in both the gyr A and par C genes. Only seven strains were resistant to nalidixic acid due to a mutation in the gyr A gene but not in the par C gene, with six and two considered intermediate to ciprofloxacin and levofloxacin, respectively. The activity of gemifloxacin was similar to that of trovafloxacin and moxifloxacin, but was more active than nalidixic acid, ciprofloxacin or levofloxacin against the gyr A mutant strains. Gemifloxacin is a valid therapeutic alternative to treat infections with N. gonorrhoeae , retaining its activity against strains already presenting a mutation in gyr A. #

Research paper thumbnail of P881 Altered outer membrane protein profiles of Pseudomonas aeruginosa highly susceptible to the effiux pump inhibitor Phe-Arg-β-naphthylamide

International Journal of Antimicrobial Agents, 2007

Both the PAO1deltamutS and the wild-type PAO1 P. aeruginosa strains (5×109−1×1010 cfu/mL) were ex... more Both the PAO1deltamutS and the wild-type PAO1 P. aeruginosa strains (5×109−1×1010 cfu/mL) were exposed to agar plates containing different antibiotic concentrations (range 0.25-256 mg/L) of tobramycin (TOB), ceftazidime (CAZ), imipenem (IMP), ciprofloxacin (CIP), and levofloxacin (LEV). Sixty five mutants recovered from plates immediately below the mutant prevention concentration were selected and susceptibility (standard CLSI agar dilution) to different antibiotics was determined. Topoisomerase (II and IV) mutations, expression of efflux pumps (MexAB-OprM, MexCD-OprJ, and MexXY) and AmpC b-lactamase, and OprD deficiency were analyzed in selected mutants. Results: The original PAO1deltamutS strain was less susceptible than its parental wild-type PAO1 strain for CAZ (8 and 1 mg/L, respectively) and TOB (2 and 0.5 mg/L). Mutants derived form the PAO1deltamutS strain were obtained in plates with higher CAZ, IMP, or TOB antibiotic concentrations (1−2 log dilutions) than those permitting the growth of mutants originated in normo-mutable PAO1 strain. Indeed mutants obtained from PAO1deltamutS strain were regularly less susceptible (1−4 log dilutions) than those selected form the wild-type PAO1 strain. Mutants selected on CAZ and IMP have reduced susceptibility restricted to b-lactam antibiotics. In these mutants, the MICs and enzymatic activity were compatible with a higher production of chromosomal AmpC enzyme in the case of CAZ selected mutants, whereas AmpC hyper-production superimposed with OprD reduction was observed in the case of IMP. In mutants selected with CIP or LEV, overproduction of efflux pumps was mainly observed with PAO1 strain and overproduction of pumps superimposed with gyrA mutations with PAO1deltamutS strain. Conclusions: The higher antibiotic resistance levels of mutants derived from dense populations of PAO1deltamutS P. aeruginosa when compared with those from the corresponding normo-mutable PAO1 wild-type strain might result from the selection of cells carrying double mutations. Hyper-mutable strains contribute to the single-step selection of variants with higher levels of antibiotic resistance.

Research paper thumbnail of P879 Cloning of a mdfA-like gene, encoding an effiux pump of an Acinetobacter baumannii clinical isolate

International Journal of Antimicrobial Agents, 2007

association of the different amino acid substitutions with resistance patterns to other fluoroqui... more association of the different amino acid substitutions with resistance patterns to other fluoroquinolones.

Research paper thumbnail of Characterization of sparfloxacin-resistant mutants of Staphylococcus aureus obtained in vitro

International Journal of Antimicrobial Agents, 2001

A sparfloxacin-susceptible clinical isolate of Staphylococcus aureus was grown in increased conce... more A sparfloxacin-susceptible clinical isolate of Staphylococcus aureus was grown in increased concentrations of sparfoxacin. The presence of mutations in gyrA, gyrB, grlA and grlB genes was analyzed. The primary point mutation was located in the gyrA gene (Glu-88 to Lys). Two further mutation steps appeared in the amino acid change Ser-80 to Tyr in GrlA. No mutations occurred in the gyrB or grlB genes. Efflux pumps involved in the increase of resistance were also found to affect norfloxacin and ciprofloxacin. This effect may be related to NorA. An overexpression of NorA, may be associated with the increase of the MIC of norfloxacin from 32 mg/l to \200 mg/l in the final mutant. The MICs levels of sparfloxacin were affected by unknown mechanism.

Research paper thumbnail of Antibiotic resistance in orthopaedic surgery: acute knee prosthetic joint infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae

European Journal of Clinical Microbiology & Infectious Diseases, 2010

The aim of this study was to describe the prevalence and characteristics of knee prosthetic joint... more The aim of this study was to describe the prevalence and characteristics of knee prosthetic joint infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. From 2000 to 2007, 132 infections out of 5,076 arthroplasties (2.6%) were registered. Seven out of 132 infections (5.3%) were due to ESBL-producing Enterobacteriaceae, Escherichia coli in six cases and Klebsiella pneumoniae in one. Open debridement and retention of the implant was the first surgical approach and all patients received intravenous carbapenems. Relapse was documented in four cases and remission in three. Therefore, debridement without prosthesis removal was associated with a high failure rate.