In vitro activity of cefiderocol and other newly approved antimicrobials against multi-drug resistant Gram-negative pathogens recovered in intensive care units in Spain and Portugal.

OBJECTIVE: The antimicrobial resistance is a significant public health threat, particularly for healthcare-associated infections caused by carbapenem-resistant Gram-negative pathogens which are increasingly reported worldwide. The aim of this study was to provide data on the in vitro antimicrobial activity of cefiderocol and that of commercially available comparator antibiotics against a defined collection of recent clinical multi-drug resistant (MDR) microorganisms, including carbapenem resistant Gram-negative bacteria collected from different regions in Spain and Portugal. METHODS: A total of 477 clinical isolates of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia were prospectively (n=265) and retrospectively (n=212) included (2016-2019). Susceptibility testing was performed using standard broad microdilution and results were interpreted using CLSI-2021 and EUCAST-2021 criteria. RESULTS: Overall, cefiderocol showed a good activity against Enterobacterales isolates, being 99.5% susceptible by CLSI and 94.5% by EUCAST criteria. It also demonstrated excellent activity against P. aeruginosa and S. maltophilia isolates, all being susceptible to this compound considering CLSI breakpoints. Regarding A. baumannii (n=64), only one isolate was resistant to cefiderocol. CONCLUSIONS: Our results are in agreement with other studies performed outside Spain and Portugal highlighting its excellent activity against MDR gram-negative bacteria. Cefiderocol is a therapeutic alternative to those available for the treatment of infections caused by these MDR bacteria.

Treatment guidelines for multidrug-resistant Gram-negative microorganisms.

In recent years, new antimicrobials have been introduced in therapeutics, including new beta-lactam-beta-lactamase inhibitor combinations and cefiderocol in response to therapeutic needs in the face of increasing resistance. There are also different treatment guidelines for infections caused by these microorganisms that have been approved by different professional societies, including those of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Disease Society of America (IDSA) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). All of them are based on scientific evidence, but with differences in the weight of expert opinion in their recommendations. Both ESCMID and IDSA include recommendations for the treatment of extended-spectrum beta-lactamase-producing microorganisms. The IDSA is the only one including AmpC producers, all address the treatment of infections caused by carbapenem-resistant Enterobacterales and Acinetobacter baumannii and multidrug-resistant or difficult-to-treat Pseudomonas aeruginosa, and the IDSA and SEIMC include recommendations on the treatment of Stenotrophomonas maltophilia. Future guidelines should integrate new antimicrobials and new innovative management options not covered by current guidelines.

Antibacterial spectrum of cefiderocol.

Cefiderocol, a siderophore catechol cephalosporin, recently introduced in the market has been developed to enhance the in vitro activity of extended spectrum cephalosporins and to avoid resistance mechanisms affecting cephalosporins and carbapenems. The in vitro study of cefiderocol in the laboratory requires iron depleted media when MIC values are determined by broth microdilution. Disk diffusion presents good correlation with MIC values. In surveillance studies and in clinical trials it has been demonstrated excellent activity against Gram-negatives, including carbapenemase producers and non-fermenters such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Few cefiderocol resistant isolates have been found in surveillance studies. Resistance mechanisms are not directly associated with porin deficiency and or efflux pumps. On the contrary, they are related with gene mutations affecting iron transporters, AmpC mutations in the omega loop and with certain beta-lactamases such us KPC-variants determining also ceftazidime-avibactam resistance, certain infrequent extended-spectrum betalactamases (PER, BEL) and metallo-beta-lactamases (certain NDM variants and SPM enzyme).

COVID-19: Impact on prescribing and antimicrobial resistance.

The onset of the COVID-19 pandemic challenged healthcare systems focusing their activity on patients infected with SARS-CoV-2. Previous experience with co-infections and superinfections in patients infected with other coronaviruses (SARS-CoV and MERS), the influenza patients admitted to hospitals and prevention of the unknown led to the increased empirical use of broad-spectrum antibiotics in hospitals. The breakdown of antimicrobial stewardship and infection control programs determine an increase in infections due to multidrug-resistant bacteria, particularly in intensive care units. Most of these infections are related to high-risk carbapenemase-producing clones and occasionally with resistance to new ß-lactam-ß-lactamase inhibitor combinations. On the contrary, in the primary care, there has been a decrease in the use of antimicrobials during the first wave, although it would not have had a significant impact on pathogens associated with community-acquired infections. The accumulated experience reaffirms the need to maintain antimicrobial stewardship and infection control programs in future health crises.

Etiology and antimicrobial susceptibility profiles of anaerobic bacteria isolated from clinical samples in a university hospital in Madrid, Spain.

BACKGROUND: The anaerobic infection management is usually based on empirical treatment because anaerobic culture techniques take a long time due to their fastidious nature. The aim of this study was to analyze the etiological profile of severe anaerobic infections and AST data from clinical anaerobic bacteria isolated in a tertiary hospital in Madrid (Spain). MATERIAL AND METHODS: A consecutive study was carried out over 19 months in Ramón y Cajal Universitary Hospital, Madrid. Clinical samples were processed in appropriate anaerobic media and incubated using Anoxomat system. Identification was performed by MALDI-TOF. AST were determined with gradient diffusion method using EUCAST (penicillin, co-amoxiclav, imipenem, clindamycine and metronidazole) or CLSI (cefoxitin) breakpoints. RESULTS: During the period of study, 503 anaerobic microorganisms isolated from 424 clinical samples were included. Twenty-six percent of the cultures were monomicrobial, while 70.0% also contained aerobic bacteria. The most common source of infection was abscesses (26%), while blood infections represented the 11%. Anaerobic gram-negative bacilli were predominant (41%), being Bacteroides fragilis (13%) the most prevalent overall; anaerobic gram-positive bacilli represented 35%, anaerobic gram-positive cocci 19% and anaerobic gram-negative cocci 5%. Metronidazole and imipenem were the most effective agents tested against anaerobic bacteria, while clindamycin presented higher resistance rates. CONCLUSION: Antimicrobial susceptibility surveillance of anaerobic bacteria should be performed to monitor changes in resistance patterns and to be able to optimize empiric antimicrobial treatment. Reliable species identification and quick reporting of results would guide clinicians to select the optimal antimicrobial therapy.

Emergence of ESBL-producing Escherichia coli ST131-C1-M27 clade colonizing patients in Europe.

Background: The ST131 Escherichia coli clone is associated with the global dissemination of ESBLs. It has been hypothesized that ST131 could take advantage of better colonizing abilities. However, the data on colonization prevalence of ESBL-ST131 in European hospitals are scarce. Objectives: To assess the prevalence of the ST131 clone and its microbiological characteristics among colonizing ESBL-producing E. coli (ESBL-Ec) from hospitalized patients in four European hospitals (Berlin, Geneva, Madrid and Utrecht) during the R-GNOSIS study. Methods: ESBL-Ec isolates (n = 688) were obtained from rectal swabs of hospitalized patients from March 2014 to February 2015 using selective media. The ST131 clone and its subclones were sought using PCR and positive isolates were further studied. blaESBL genes were characterized (PCR and sequencing), antibiotic susceptibility testing was performed, clonal relationships were studied by PFGE and fimH allele and O type (PCR) were assessed. Results: ST131 prevalence was 20.5% (141/688); C1/H30R1 isolates were significantly more prevalent in Geneva (49%) and C2/H30Rx in Madrid (67%). C1/H30R1 isolates showed less resistance to amikacin than C2/H30Rx (4% versus 35%) and all were susceptible to penicillin/inhibitor combinations. CTX-M-15 was the most common enzyme (49%) followed by CTX-M-27 (27%). C1/H30R1 isolates were significantly associated with CTX-M-27 (72%) and all of these isolates belonged to the C1-M27 clade. Moreover, C2/H30Rx isolates and CTX-M-15 were also significantly related (88%). Conclusions: The predominance of C2/H30Rx-CTX-M-15 in Madrid and C1/H30R1-CTX-M-27 in Geneva demonstrates a changing epidemiology of ESBLs in Europe caused by ST131 subclones; in particular, the emergence of the C1-M27 clade in Europe.

Predictors of outcome in patients with severe sepsis or septic shock due to extended-spectrum ß-lactamase-producing Enterobacteriaceae.

PURPOSE: There are few data in the literature regarding sepsis or septic shock due to extended-spectrum ß-lactamases (ESBL)-producing Enterobacteriaceae (E). The aim of this study was to assess predictors of outcome in septic patients with bloodstream infection (BSI) caused by ESBL-E. METHODS: Patients with severe sepsis or septic shock and BSI due to ESBL-E were selected from the INCREMENT database. The primary endpoint of the study was the evaluation of predictors of outcome after 30 days from development of severe sepsis or septic shock due to ESBL-E infection. Three cohorts were created for analysis: global, empirical-therapy and targeted-therapy cohorts. RESULTS: 367 septic patients were analysed. Overall mortality was 43.9% at 30 days. Escherichia coli (62.4%) and Klebsiella pneumoniae (27.2%) were the most frequent isolates. ß-lactam/ß-lactamase inhibitor (BLBLI) combinations were the most empirically used drug (43.6%), followed by carbapenems (29.4%). Empirical therapy was active in vitro in 249 (67.8%) patients, and escalation of antibiotic therapy was reported in 287 (78.2%) patients. Cox regression analysis showed that age, Charlson Comorbidity Index, McCabe classification, Pitt bacteremia score, abdominal source of infection and escalation of antibiotic therapy were independently associated with 30-day mortality. No differences in survival were reported in patients treated with BLBLI combinations or carbapenems in empirical or definitive therapy. CONCLUSIONS: BSI due to ESBL-E in patients who developed severe sepsis or septic shock was associated with high 30-day mortality. Comorbidities, severity scores, source of infection and antibiotic therapy escalation were important determinants of unfavorable outcome.

Epidemiology of antibiotic resistance in Pseudomonas aeruginosa. Implications for empiric and definitive therapy.

Pseudomonas aeruginosa is one of the major pathogens causing hospital-acquired infections. It can easily develop antibiotic resistance through chromosomal mutations or by horizontal acquisition of resistant determinants. The increasing prevalence of multi-drug-resistant (MDR) or extensively-drug-resistant (XDR) P. aeruginosa isolates is associated with the dissemination of the so-called high-risk-clones, such as ST175. Infections caused by MDR/XDR are a cause of concern as they compromise the selection of appropriate empiric and definitive antimicrobial treatments. Introduction of new antibiotics with potent activity against MDR/XDR P. aeruginosa opens new horizons in the treatment of these infections.

[Epidemiology of multi-drug resistant gramnegative bacilli]. / Epidemiología de los bacilos gramnegativos multirresistentes.

Current antimicrobial resistance in Gram negative bacilli is particularly worrisome due to development of resistance to all available antimicrobial agents. This situation dramatically limits therapeutic options. The microorganisms acquire a multiresistance phenotype as a consequence of different complex processes in which the antimicrobials acts as selective driver of resistance. Dissemination of multiresistant bacteria is driven by the expansion of the high-risk clones. These clones can be selected in the presence of antimicrobials allowing their persistence over time.

Multisite Evaluation of Cepheid Xpert Carba-R Assay for Detection of Carbapenemase-Producing Organisms in Rectal Swabs.

Rapid identification of patients who are colonized with carbapenemase-producing organisms (CPO) is included in multiple national guidelines for containment of these organisms. In a multisite study, we evaluated the performance of the Cepheid Xpert Carba-R assay, a qualitative diagnostic test that was designed for the rapid detection and differentiation of the blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP-1 genes from rectal swab specimens. A double rectal swab set was collected from 383 patients admitted at four institutions (2 in the United States, 1 in the United Kingdom, 1 in Spain). One swab was used for reference culture (MacConkey broth containing 1 mg/liter of meropenem and subcultured to a MacConkey agar plate with a 10-µg meropenem disk) and for sequencing of DNA obtained from carbapenem-nonsusceptible isolates for carbapenemase identification. The other swab was used for the Xpert Carba-R assay. In addition to the clinical rectal swabs, 250 contrived specimens (108 well-characterized CPO and 142 negative controls spiked onto negative rectal swabs) were tested. Overall, 149/633 (23.5%) samples were positive by the Xpert Carba-R assay. In 6 samples, multiple targets were detected (4 VIM/OXA-48, 1 IMP-1/NDM, and 1 NDM/KPC). The Xpert Carba-R assay detected 155 targets (26 IMP-1, 30 VIM, 27 NDM, 33 KPC, 39 OXA-48) within a time range of 32 to 48 min. The sensitivity, specificity, and positive and negative predictive values of the Xpert Carba-R assay compared to those of the reference culture and sequencing results were 96.6% (95% confidence interval [CI], 92.2% to 98.9%), 98.6% (95% CI, 97.1% to 99.4%), 95.3%, and 99.0%, respectively. The Cepheid Xpert Carba-R assay is an accurate and rapid test to identify rectal colonization with CPO, which can guide infection control programs to limit the spread of these organisms.

The rise of ampicillin-resistant Enterococcus faecium high-risk clones as a frequent intestinal colonizer in oncohaematological neutropenic patients on levofloxacin prophylaxis: a risk for bacteraemia?

Levofloxacin extended prophylaxis (LEP), recommended in oncohaematological neutropenic patients to reduce infections, might select resistant bacteria in the intestine acting as a source of endogenous infection. In a prospective observational study we evaluated intestinal emergence and persistence of ampicillin-resistant Enterococcus faecium (AREfm), a marker of hospital adapted high-risk clones. AREfm was recovered from the faeces of 52 patients with prolonged neutropenia after chemotherapy, at admission (Basal), during LEP, and twice weekly until discharge (Pos-LEP). Antibiotic susceptibility, virulence traits and population structure (pulsed-field gel electrophoresis and multilocus sequence typing) were determined and compared with bacteraemic isolates. Gut enterococcal population was monitored using a quantitative PCR quantification approach. AREfm colonized 61.4% of patients (194/482 faecal samples). Sequential AREfm acquisition (25% Basal, 36.5% LEP, 50% Pos-LEP) and high persistent colonization rates (76.9-89.5%) associated with a decrease in clonal diversity were demonstrated. Isolates were clustered into 24 PFGE-patterns within 13 sequence types, 95.8% of them belonging to hospital-associated Bayesian analysis of population structure subgroups 2.1a and 3.3a. Levofloxacin resistance and high-level streptomycin resistance were a common trait of these high-risk clones. AREfm-ST117, the most persistent clone, was dominant (60.0% isolates, 32.6% patients). It presented esp gene and caused 18.2% of all bacteraemia episodes in 21% of patients previously colonized by this clone. In AREfm-colonized patients, intestinal enrichment in the E. faecium population with a decline in total bacterial load was observed. AREfm intestinal colonization increases during hospital stay and coincides with enterococci population enrichment in the gut. Dominance and intestinal persistence of the ST117 clone might increase the risk of bacteraemia.

Non-diphtheriae Corynebacterium species: an emerging respiratory pathogen.

The purpose of the study was to describe the microbiological and clinical features of ten cases of lower respiratory tract infection due to Corynebacterium striatum, Corynebacterium propinquum and Corynebacterium pseudodiphtheriticum. Respiratory samples were recovered from hospitalised patients who were diagnosed of pneumonia and exacerbations of chronic respiratory infections. The samples were Gram-stained and seeded on conventional bacterial growing media. Bacteria were identified by matrix-assisted linear desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF MS). Antibiotic susceptibility was tested by the disk diffusion method. All patients presented an acute respiratory onset, most of them in the context of an underlying disease and/or immunosuppression. In all patients, the microscopical examination of Gram-stained respiratory samples showed numerous polymorphonuclear cells and Gram-positive bacilli, suggestive of the Corynebacterium morphotype. A pure culture growth of Corynebacterium was obtained in the majority (72 %) of samples. The conclusions are that non-diphtheriae Corynebacterium species are an emerging cause of respiratory infection among patients with chronic respiratory disease and/or immunosuppression, and cannot always be considered as mere colonisers. The microorganism's predominance in Gram-stained purulent respiratory samples together with abundant growth in the culture is the key for the microbiological diagnosis.

Emergence and outbreak of carbapenemase-producing KPC-3 Klebsiella pneumoniae in Spain, September 2009 to February 2010: control measures.

This report describes the epidemiological features of the first outbreak caused by KPC3 carbapenemase-producing Klebsiella pneumoniae (KPC-3-KP) in Spain and how it was effectively controlled. From 16 September 2009 to the end of February 2010, seven patients infected or colonised with KPC-3-KP were detected. Stool surveillance cultures were recovered from patients, doctors, nurses, nursing assistants, cleaners and hospital porters working in the affected units. Hand swabs were taken from workers and patients' relatives for culturing. Environmental samples were also taken. Patients infected or colonised with KPC-3-KP were placed in single rooms under contact precautions and 4% chlorhexidine soap was used for their daily hygiene. Staff attended educational seminars and workshops on hand hygiene and isolation of patients. An alcohol-based disinfectant was used for surface cleaning and disinfecting. The floor was cleaned with a disinfectant containing benzalkonium chloride and didecyldimethylammonium. All samples collected were negative for KPC-3-KP. After implementing the control measures, no further cases were reported in the affected units. All cases had comorbidities, long hospital stay and aggressive/intensive antimicrobial treatment. This study emphasises the importance of early intensification of infection control to interrupt the transmission of KPC-producing organisms.

Programas de optimización de uso de antimicrobianos (PROA) en hospitales españoles: documento de consenso GEIH-SEIMC, SEFH y SEMPSPH / Programs for optimizing the use of antibiotics (PROA) in Spanish hospitals: GEIH-SEIMC, SEFH and SEMPSPH consensus document

Los antimicrobianos son fármacos distintos al resto. Su eficacia en la reducción de la morbilidad y la mortalidad es muy superior a la de otros grupos de medicamentos. Por otra parte, son los únicos fármacos con efectos ecológicos, de manera que su administración puede contribuir a la aparición y diseminación de resistencias microbianas. Finalmente, son utilizados por médicos de prácticamente todas las especialidades. La actual complejidad en el manejo de las enfermedades infecciosas y del aumento de las resistencias hace imprescindible el establecimiento de programas de optimización del uso de antimicrobianos en los hospitales (PROA).Este documento de consenso define los objetivos de los PROA (mejorar los resultados clínicos de los pacientes con infecciones, minimizar los efectos adversos asociados a la utilización de antimicrobianos, incluyendo aquí las resistencias, y garantizar la utilización de tratamientos coste-eficaces) y establece recomendaciones para su implantación en los hospitales españoles. Las líneas maestras de las recomendaciones son: la constitución de un equipo multidisciplinario de antibióticos, dependiente de la Comisión de Infecciones. Los PROA necesitan ser considerados programas institucionales de los hospitales donde se desarrollen. Deben incluir objetivos específicos y resultados cuantificables en función de indicadores, y basarse en la realización de actividades encaminadas a mejorar el uso de antimicrobianos, principalmente mediante actividades formativas y medidas no impositivas de ayuda a la prescripción (AU)

The antimicrobial agents are unique drugs for several reasons. First, their efficacy is higher than other drugs in terms of reduction of morbidity and mortality. Also, antibiotics are the only group of drugs associated with ecological effects, because their administration may contribute to the emergence and spread of microbial resistance. Finally, they are used by almost all medical specialties. Appropriate use of antimicrobials is very complex because of the important advances in the management of infectious diseases and the spread of antibiotic resistance. Thus, the implementation of programs for optimizing the use of antibiotics in hospitals (called PROA in this document) is necessary. This consensus document defines the objectives of the PROA (namely, to improve the clinical results of patients with infections, to minimise the adverse events associated to the use of antimicrobials including the emergence and spread of antibiotic resistance, and to ensure the use of the most cost-efficacious treatments), and provides recommendations for the implementation of these programs in Spanish hospitals. The key aspects of the recommendations are as follows. Multidisciplinary antibiotic teams should be formed, under the auspices of the Infection Committees. The PROA need to be considered as part of institutional programs and the strategic objectives of the hospital. The PROA should include specific objectives based on measurable indicators, and activities aimed at improving the use of antimicrobials, mainly through educational activities and interventions based more on training activities directed to prescribers than just on restrictive measures (AU)

High-density fecal Enterococcus faecium colonization in hospitalized patients is associated with the presence of the polyclonal subcluster CC17.

Enterococcus faecium belonging to the polyclonal subcluster CC17, with a typical ampicillin-resistant E. faecium (AREfm) phenotype, have become prevalent among nosocomial infections around the world. High-density intestinal AREfm colonization could be one of the factors contributing to the successful spread of these pathogens. We aimed to quantify the enterococcal intestinal colonization densities in stool samples from AREfm-colonized and non-colonized patients using fluorescent in situ hybridization (FISH). Stool samples were collected from AREfm-colonized (n = 8) and non-colonized (n = 8) patients. The relative number of Enterococcus faecalis and E. faecium was determined by FISH using specific 16S rRNA probes, while the total amount of bacterial cells was counted by staining the sample with 4',6-diamidino-2-phenylindole (DAPI). The median bacterial cell numbers in fecal samples, counted by DAPI staining, were 7.7 × 10(9) and 4.8 × 10(9) cells/g for AREfm-colonized and non-colonized patients, respectively (p = 0.34). The E. faecium densities in AREfm-colonized patients, accounting for 0.5-7% of all fecal bacterial cells, exceeded E. faecalis levels by over ten-fold. E. faecium was not detected in non-colonized patients. This study demonstrated high E. faecium cell densities in stool samples from patients colonized with AREfm. Increased cell densities may contribute to host-to-host transmission and environmental contamination, facilitating the spread of AREfm in the hospital setting.

[Programs for optimizing the use of antibiotics (PROA) in Spanish hospitals: GEIH-SEIMC, SEFH and SEMPSPH consensus document]. / Programas de optimización de uso de antimicrobianos (PROA) en hospitales españoles: documento de consenso GEIH-SEIMC, SEFH y SEMPSPH.

The antimicrobial agents are unique drugs for several reasons. First, their efficacy is higher than other drugs in terms of reduction of morbidity and mortality. Also, antibiotics are the only group of drugs associated with ecological effects, because their administration may contribute to the emergence and spread of microbial resistance. Finally, they are used by almost all medical specialties. Appropriate use of antimicrobials is very complex because of the important advances in the management of infectious diseases and the spread of antibiotic resistance. Thus, the implementation of programs for optimizing the use of antibiotics in hospitals (called PROA in this document) is necessary. This consensus document defines the objectives of the PROA (namely, to improve the clinical results of patients with infections, to minimise the adverse events associated to the use of antimicrobials including the emergence and spread of antibiotic resistance, and to ensure the use of the most cost-efficacious treatments), and provides recommendations for the implementation of these programs in Spanish hospitals. The key aspects of the recommendations are as follows. Multidisciplinary antibiotic teams should be formed, under the auspices of the Infection Committees. The PROA need to be considered as part of institutional programs and the strategic objectives of the hospital. The PROA should include specific objectives based on measurable indicators, and activities aimed at improving the use of antimicrobials, mainly through educational activities and interventions based more on training activities directed to prescribers than just on restrictive measures.

Programas de optimización de uso de antimicrobianos (PROA) en hospitales españoles: documento de consenso GEIH-SEIMC, SEFH y SEMPSPH / No disponible

Los antimicrobianos son fármacos distintos al resto. Su eficacia en términos de curación y reducción de mortalidad es muy superior a la de otros grupos de medicamentos,habiéndose demostrado que la indicación de antimicrobianosinadecuados en determinadas situaciones clínicas es un factorindependiente de aumento del riesgo de mortalidad. Por otra parte, son los únicos fármacos con efectos ecológicos, de manera que su administación afecta tanto al paciente que los recibe como al resto, dado que pueden contribuir a la aparicióny diseminación de resistencias microbianas. Finalmente, sonutilizados por médicos de prácticamente todas las especialidades.La complejidad actual motivada por los avances en el conocimiento del manejo de las nfermedades infecciosas y del aumento de las resistencias hace imprescindible el establecimiento de programas de optimización del uso de antimicrobianos en los hospitales (PROA). Este documento de consenso define los objetivos de losPROA (por este orden: mejorar los resultados clínicos de los pacientes con infecciones, minimizar los efectosadversos asociados a la utilización de antimicrobianos, incluyendo aquí la aparición y diseminación deresistencias, y garantizar la utilización de tratamientos coste-eficaces) y establece recomendaciones para suimplantación en los hospitales españoles. Las líneas maestras de las recomendaciones son las siguientes: eldiseño y desarrollo de los PROA debe basarse en la constituciónde un equipo multidisciplinar de antibióticos, dependiente de la Comisión de Infecciones. Para posibilitar su éxito, estos programas necesitan ser considerados comoparte de la propia institución sanitaria y formar parte de los objetivos de los centros donde se desarrollen (AU)

No disponible

Lesiones cutáneas múltiples pormycobacterium chelonae en huésped inmunocompetente / Multiple cutaneous lesions by mycobacterium chelonae in an immunocompetent host

Mycobacterium chelonae es una micobacteria no tuberculosa (MNTB) de rápido crecimiento, que en el huésped inmunocompetente puede producirlesiones cutáneas localizadas relacionadas con traumatismos.Presentamos dos casos de infección cutánea en hermanas inmunocompetentes quienes desarrollaron lesiones múltiples en muslos y piernas relacionadascon el uso de cera depilatoria. Del cultivo de la lesión se aisló M. chelonae sensible a eritromicina. Se trataron con claritromicina durante 3 mesescon respuesta clínica favorable (AU)

Mycobacterium chelonae is a rapidly growing mycobacterium. In inmunocompetent host cutaneous infection is ussualy isolated, localized and associated with trauma.Two inmunocompetent sisters who consulted because of multiple skin lesion localized in legs and thigs associated to depilation are reported. The cultureof skin lesion showed M. chelonae (AU)

Complex clonal and plasmid epidemiology in the first outbreak of Enterobacteriaceae infection involving VIM-1 metallo-beta-lactamase in Spain: toward endemicity?

BACKGROUND: We report the emergence and spread of metallo-beta-lactamases (MBLs) among enterobacterial isolates at Ramón y Cajal University Hospital (Madrid, Spain). METHODS AND RESULTS: During the period from March 2005 through September 2006, 25 patients (52% of whom were in the intensive care unit) were infected and/or colonized with single or different MBL-producing Enterobacteriaceae isolates (Klebsiella pneumoniae, 14 patients; Enterobacter cloacae, 12 patients; Escherichia coli, 1 patient; and/or Klebsiella oxytoca, 1 patient). Clonal analysis (XbaI pulsed-field gel electrophoresis) revealed that all K. pneumoniae isolates belonged to the same clone, but 6 patterns were found among the E. cloacae isolates. Carbapenems were affected to different degrees (minimum inhibitory concentration, < or = 1 to > 8 microg/mL), as were aminoglycosides and ciprofloxacin. The bla(VIM-1) MBL gene was present in all isolates; in addition, the bla(SHV-12) extended-spectrum beta-lactamase gene was detected in K. pneumoniae and E. coli isolates. The bla(VIM-1) gene was detected within a 4.0-kb class 1 integron (bla(VIM-1)-aacA4-dfrII-aadA1-catB2) in K. pneumoniae and E. coli and in a 2.5-kb class 1 integron (bla(VIM-1)-aacA4-aadA1) in E. cloacae and K. oxytoca isolates. The bla(VIM-1) gene was transferable (filter-mating) in 14 of 14 K. pneumoniae isolates, 4 of 11 E. cloacae isolates, and 1 of 1 E. coli isolate. A 60-kb plasmid belonging to the IncI1 group was detected in the epidemic VIM-1-K. pneumoniae clone. Plasmids of 300- or 435-kb belonging to IncH12 group were found among E. cloacae isolates. CONCLUSIONS: K. pneumoniae-MBL monoclonal epidemics coexisted with E. cloacae-MBL multiclonal epidemics in our hospital. The spread of the bla(VIM-1) gene among Enterobacteriaceae was driven by clonal spread associated with intergeneric plasmid transfer with different class I integron platforms. Such complex epidemiology might anticipate endemicity and should be considered for the design of containment epidemiology strategies.

Genetic and phenotypic differences among Enterococcus faecalis clones from intestinal colonisation and invasive disease.

This study investigated the differences among Enterococcus faecalis isolates from the intestinal compartment of healthy volunteers (n = 36), intensive care unit (ICU) patients (n = 29) and blood isolates (n = 31) from the same institution, in comparison with seven epidemic clones from other institutions. In general, isolates from colonised ICU patients and from bacteraemic patients showed higher rates of antimicrobial resistance than isolates from colonised healthy volunteers, particularly for erythromycin and aminoglycosides. The proportion of isolates/clone was 1.05 in the community, 2.63 in the ICU, and 1.47 among bacteraemic cases, suggesting low clonal variation in ICUs. Two clones, RENC1 and RENC2, were frequently found as intestinal colonisers of ICU patients, and RENC1 was also found to colonise healthy volunteers. These two clones were a cause of bacteraemia in the institution studied, and RENC2 was also detected in various other Spanish hospitals. Both RENC1 and RENC2 were esp+, bacteriocin producers, and were resistant to all antibiotics tested except vancomycin and ampicillin. RENC1 produced haemolysin whereas RENC2 produced protease. The ace, agg, cylA, esp and gelE genes were more common among colonising strains from ICU patients than among isolates from individuals in the community. In both colonised groups (ICUs and the community), 40-50% of isolates harbouring the gelE and cylA genes did not express the corresponding phenotypes. Thus, the study indicated that particular E. faecalis clones might be well-adapted to hospital environments, and that surveillance should be directed specifically towards rapid detection of these disseminating clones in order to prevent infections and clonal spread.