Carbapenem alternatives for treatment of bloodstream infections due to AmpC producing enterobacterales.

INTRODUCTION: Carbapenems (CR) have traditionally been the first line treatment for bacteremia caused by AmpC-producing Enterobacterales. However, CR have a high ecological impact, and carbapenem-resistant strains continue rising. Thus, other treatment alternatives like Piperacillin-Tazobactam (P-T) or Cefepime (CEF) and oral sequential therapy (OST) are being evaluated. METHODS: We conducted a retrospective, single-centre observational study. All adult patients with AmpC-producing Enterobacterales bacteremia were included. The primary endpoint was clinical success defined as a composite of clinical cure, 14-day survival, and no adverse events. We evaluated the evolution of patients in whom OST was performed. RESULTS: Seventy-seven patients were included, 22 patients in the CR group and 55 in the P-T/CEF group (37 patients received CEF and 18 P-T). The mean age of the patients was higher in the P-T/CEF group (71 years in CR group vs. 76 years in P-T/CEF group, p = 0.053). In the multivariate analysis, age ≥ 70 years (OR 0.08, 95% CI [0.007-0.966], p = 0.047) and a Charlson index ≥ 3 (OR 0.16, 95% CI [0.026-0.984], p = 0.048), were associated with a lower clinical success. Treatment with P-T/CEF was associated with higher clinical success (OR 7.75, 95% CI [1.273-47.223], p = 0.026). OST was performed in 47% of patients. This was related with a shorter in-hospital stay (OST 14 days [7-22] vs. non-OST 18 days [13-38], p = 0.005) without difference in recurrence (OST 3% vs. non-OST 5%, p = 0.999). CONCLUSIONS: Targeted treatment with P-T/CEF and OST could be safe and effective treatments for patients with AmpC-producing Enterobacterales bacteremia.

Gastrointestinal colonization by OXA-48-producing Enterobacterales: risk factors for persistent carriage.

Carbapenem-resistant Enterobacterales (CRE) infections are a major health problem. Intestinal colonization is a key factor in developing infection. However, factors associated with persistent colonization by CRE are unknown. The aim of the study was to identify factors associated with persistent CRE gut colonization. This is a retrospective, single-centre, observational study of adult patients with CRE gut colonization between January 2015 and January 2020. Epidemiologic characteristics, comorbidities, infectious events, duration of hospitalization and antimicrobial treatment received in the follow-up period were collected. Colonization was defined as isolation in at least 2 rectal swab culture samples of CRE. Decolonization was defined as 3 negative rectal swab cultures or 2 negative cultures and a negative molecular test. A cohort of 86 patients with CRE gut colonization was selected: 44 patients with spontaneous decolonization (DC) and 42 patients with persistent colonization (PC). The mean follow-up period was 24 months (IQR 14-33) in the DC group vs. 25 months (IQR 16-36) in the PC group (p = 0.478). Patient characteristics were similar between both groups. Colonization by other MDR microorganisms was high (44 patients, 51%) and slightly more common in the PC group (PC 60% vs. DC 43%, p = 0.139). The use of ceftazidime-avibactam was more common among the PC group (PC 33% vs. DC 14%, p = 0.041). We observed a higher percentage of antimicrobial therapy in the previous 30 days (PC 68% vs. DC 57%, p = 0.371) and 90 days (PC 81% vs. DC 82%, p = 0.353) in the PC group. Multivariable analysis showed that patients that have received ceftazidime-avibactam therapy (OR 4.9 95% CI [1.45-16.39], p = 0.010), and those colonized by other MDR microorganisms (OR 2.5, 95% CI [0.96-6.25], p = 0.060) presented a higher risk of PC. Ceftazidime-avibactam use and colonization by other MDR microorganisms might be associated with CRE persistent gut colonization.

Ceftazidime-avibactam treatment in bacteremia caused by OXA-48 carbapenemase-producing Klebsiella pneumoniae.

Therapeutic options for bacteremia caused by carbapenem-resistant Enterobacterales (CRE) OXA-48-type are limited. The objective of this study was to analyze clinical success of CAZ-AVI compared with best available therapy (BAT) in patients with Klebsiella pneumoniae carbapenemase-producing OXA-48-type bacteremia (CRKp-OXA-48). We conducted a retrospective, single-center observational study in adult patients with CRKp-OXA-48 between December 2015 and May 2019. We collected the patients' clinical and epidemiological characteristics, antibiotic treatment (CAZ-AVI vs. BAT), and evolution. Factors associated with clinical success were analyzed using binary logistic regression. The study included 76 patients with CRKp-OXA-48-type bacteremia 33 received CAZ-AVI and 43 BAT. CAZ-AVI was mainly used in monotherapy (91%). Clinical success was more common in patients < 70-year-old (OR 4.79, 95% CI [1.435-16.002], p = 0.011) and CAZ-AVI treatment (OR 6.69, 95% CI [1.68-26.604], p = 0.007). Kaplan-Meier survival curve of 14-day mortality showed a lower mortality in patients who received CAZ-AVI (log rank 0.013). However, CAZ-AVI did not achieve statistical difference in IPTW for 14- and 30-day mortality (aOR 0.1, 95% CI [0.02-1.22], p = 0.076 and aOR 1.7, 95% CI [0.48-5.98], p = 0.413, respectively). CAZ-AVI treatment might be associated with a greater clinical success in CRKp-OXA-48 bacteremia.

Mortality-related factors in patients with OXA-48 carbapenemase-producing Klebsiella pneumoniae bacteremia.

ABSTRACT: Carbapenemase-producing Enterobacterales constitute a serious public health threat; however, information on the oxacilinasa (OXA-48)-type is limited. The objective of the study was to evaluate the risk factors associated with 14-day mortality for patients with bacteremia due to OXA-48 carbapenemase-producing Klebsiella pneumoniae.We conducted a retrospective, single-center observational study of adult patients with K. pneumoniae bacteremia, classifying the strains as carbapenem-susceptible K. pneumoniae (CSKp) and carbapenem-resistant K. pneumoniae (CRKp). All of the CRKp strains were the OXA-48-type.The study included 202 cases of bacteremia: 114 due to CSKp and 88 due to CRKp. The clinical cure rate was higher for the patients with CSKp (85% vs 69% for CSKp and CRKp, respectively; P = .010), while the 14-day mortality rate was lower (13% vs 30%, P = .005). An INCREMENT-CPE score ≥7 (HR 3.05, 95% CI 1.50-6.25, P = .002) was the only independent factor associated with 14-day mortality for the patients with Klebsiella spp. bacteremia. Other factors related to 14-day mortality were a rapidly fatal prognosis (McCabe) (HR 7.1, 95% CI 2.75-18.37, P < .001), dementia (HR 5.9, 95% CI 2.0-7.43, P = .001), and a high-risk source of infection (HR 2.7, 95% CI 1.06-6.82, P = .038).The most important factors associated with 14-day mortality for the patients with K. pneumoniae bacteremia was an INCREMENT-CPE score ≥7, dementia, a McCabe score indicating a rapidly fatal prognosis and a high-risk source of infection. We found no relationship between a poorer outcome and CRKp isolation or inadequate antibiotic therapy.

Role of Pneumocystis jirovecii in patients with different pulmonary underlying condition using a nested-PCR.

OBJECTIVE: The prevalence of Pneumocystis jirovecii colonization and its role in pulmonary disease remains unclear. PCR methods have shown an improved sensitivity in the detection of this fungus. It has been suggested that the PCR results be combined with another test such as IFA to create a diagnostic algorithm. METHODS: A multiplex nested-PCR procedure with a 16S rRNA gene as the internal amplification control was evaluated to determine the role of P. jirovecii in pulmonary disease. RESULTS: A 20% of the 199 bronchoalveolar lavage samples were PCR-positive, 13.5% samples were PCR-inhibited, and the rate of Pneumocystis-colonisation was 6.4%. The sensitivity, specificity, positive predictive value and negative predictive value of the nested-PCR were 100%, 93%, 70% and 100%, respectively. The sensitivity of the nested-PCR was higher than the current "gold standard" immunofluorescence assay (IFA) (p< 0.0001). PCR-negative and PCR-positive patients did not show any clinical or radiological differences in the medical variables studied. CONCLUSIONS: PCR could help the diagnosis of Pneumocystis pulmonary disease given the high negative predictive value of the technique. P. jirovecii DNA can frequently be detected in healthy population, so the analysis of the patient medical history is critical to make the correct clinical decision.

Nosocomial infection by VIM-2 metallo-beta-lactamase-producing Pseudomonas putida.

Nosocomial infections caused by multidrug-resistant and carbapenem-resistant Pseudomonas putida isolates have been reported occasionally in severely ill or immunocompromised patients. Here we report the microbiological characteristics of what are believed to be the two first carbapenem-resistant VIM metallo-beta-lactamase (MBL)-producing P. putida strains in Spain, which were isolated from patients at the University Hospital Complex of Santiago de Compostela. Both patients were immunocompromised with severe underlying diseases and had been hospitalized for more than 15 days. One of them had previously been treated with a broad-spectrum therapy. Antimicrobial susceptibility testing showed that both strains were resistant to piperacillin/tazobactam, ceftazidime, cefepime, imipenem, meropenem, gentamicin, tobramycin, aztreonam, trimethoprim/sulfamethoxazole and ciprofloxacin, but sensitive to amikacin and colistin. For both isolates PCR and sequencing was positive for the bla(VIM-2) gene. Fingerprinting analysis revealed these were two different strains. One patient recovered clinically and one died; no direct link could be established between the isolation of P. putida and death. Our data expose the emergence of multidrug-resistant P. putida VIM-2 MBL, probably arising by independent horizontal transfer of resistance genes. So, although P. putida is not frequently isolated, it may survive easily in the hospital setting and occasionally cause difficult-to-treat nosocomial infections in severely ill patients.

Carbapenem-resistant Enterobacter cloacae and the emergence of metallo-beta-lactamase-producing strains in a third-level hospital (Santiago de Compostela, NW Spain).

The purpose of this paper was to investigate the occurrence of carbapenem-resistant Enterobacter cloacae in our institution, to detect the carbapenemase-associated resistance and to determine the genetic relatedness of the isolates. Species identification and antimicrobial susceptibility testing were performed using the Vitek 2 system and Etest. Multiplex polymerase chain reaction-enzyme linked immunosorbent assay (PCR-ELISA) was used for the detection of extended-spectrum beta-lactamase (ESBL)-producers. The bla (IMP) and bla (VIM) genes were amplified by PCR and sequenced. The DiversiLab System was used for strain-typing. During the period 2006-2008, 12 different isolates of carbapenem-resistant E. cloacae (2.3 %) were recovered in our laboratory. Only two positive isolates for the bla (VIM) gene were detected. The minimum inhibitory concentration (MIC) values were higher for all carbapenems in the group of non-metallo-beta-lactamase (MBL)-producers. All isolates showed MIC values

Endemic linezolid-resistant Staphylococcus epidermidis in a critical care unit.

The aim of this article was to report the emergence of patient infections with linezolid-resistant Staphylococcus epidermidis (LRSE) in a tertiary university hospital. Our objectives were to determine the molecular mechanism of the resistance, set up the genetic relationship among isolates, and analyze the relations between linezolid usage, period of treatment, and emergence of resistance in the hospital. The emergence of infection with linezolid-resistant S. epidermidis affecting 20 patients in a tertiary university hospital was investigated using repetitive sequence-based PCR (rep-PCR, DiversiLab System; BioMérieux, Inc., France). The presence of the G2576T mutation of 23S rRNA was screened by pyrosequencing. We determined the pattern of linezolid usage in the hospital as a whole and in the critical care unit that was most affected. G2576T mutation of 23S rRNA was detected in all linezolid-resistant S. epidermidis studied. Of these, 90% were genetically related and had been recovered from patients admitted to the same critical care unit. There had been an increase in linezolid usage in the hospital and in the critical care unit in the 2 years prior to the emergence of resistant strains. More strict control measures in hand washing and linezolid prescription were subsequently established, but no reduction in LRSE rates have yet been observed. Linezolid-resistant S. epidermidis emerged at our hospital, probably from a single strain originating in the critical care unit. The most likely explanation is that person-to-person spread of linezolid-resistant S. epidermidis led to skin colonization and, after linezolid treatment, this resistant staphylococci became the dominant cutaneous flora causing infection in some critical patients. In order to preserve the usefulness of this antibiotic as a therapeutic agent and to avoid a situation similar to methicillin-resistant Staphylococcus aureus, judicious use of antibiotics is essential.

[Comparison between Phoenix system and agar-based methods for antimicrobial susceptibility testing of Streptococcus spp]. / Comparación entre el sistema Phoenix y métodos basados en agar para el ensayo de sensibilidad a antibióticos en Streptococcus spp.

Introduction. Antibiotic resistance is an emerging problem among streptococcal species, especially for severe infections. Automated diagnostic systems for antimicrobial susceptibility testing, such as BD Phoenix, is a recently available instruments that makes it possible to obtain results within 12 h. Methods. Antimicrobial susceptibility testing results of the BD Phoenix system were compared to those obtained from Clinical Laboratory Standards Institute (CLSI) disk-diffusion method. Two-hundred different clinical isolates of streptococci were assayed: beta-hemolytic (n=65), viridans (n=87), S. penumoniae (n=48). Results. Overall, there was categorical agreement greater than 96.7% (94.8% for beta-hemolytic and 97.9% for viridans group) in relationship to the disk-diffusion method. The minor error rates were less than 10% for all the antibiotics. The greatest percentage of serious errors corresponded to erythromycin and clindamycin within the beta-hemolytic group (14.7%). Overall percentage of very serious errors was less 0.5%. The results for penicillin in viridans streptococci and S. pneumoniae results showed 89.7% and 91.7% of categorical agreement, respectively, using the Etest as reference. Conclusions. The automated BD Phoenix system is a very useful and effective diagnostic tool for quantitative testing of sensitivity to antibiotics in the streptococci group.

Comparación entre el sistema Phoenix y métodos basados en agar para el ensayo de sensibilidad a antibióticos en Streptococcus spp / Comparison between Phoenix system and agar-based methods for antimicrobial susceptibility testing of Streptococcus spp

Introducción. La resistencia a los antibióticos en el grupode los estreptococos es un problema emergente de especialimportancia en las infecciones graves. El sistema automatizadoBD Phoenix para identificación y antibiograma esun instrumento diagnóstico recientemente disponible quepermite obtener resultados en 12 h.Métodos. Se ha llevado a cabo un estudio comparativoentre el sistema BD Phoenix con paneles SMIC/ID-9 y el métododisco-difusión para la realización de estudios de sensibilidada antibióticos. Se utilizaron 200 aislamientos clínicosde estreptococos: betahemolíticos (n=65), viridans (n=87) yStreptococcus pneumoniae (n=48).Resultados. De forma global, en relación con el métododisco-difusión, hubo un acuerdo entre categorías superioral 96,7% (94,8% en betahemolíticos y 97,9% en viridans).Las tasas de errores menores fueron inferiores al 10% paratodos los antibióticos. El mayor porcentaje de errores gravescorrespondió a eritromicina y clindamicina dentro del grupode los betahemolíticos (14,7 %). El porcentaje global deerrores muy graves fue inferior al 0,5%. Los resultados parapenicilina en estreptococos viridans y S. pneumoniae presentaronun acuerdo entre categorías del 89,7 y 91,7% frentea Etest, respectivamente.Conclusiones. El sistema automatizado BD Phoenix esun instrumento diagnóstico de gran utilidad y efectividadpara el ensayo cuantitativo de la sensibilidad a los antibióticosen el grupo de los estreptococos (AU)

Introduction. Antibiotic resistance is an emergingproblem among streptococcal species, especially for severeinfections. Automated diagnostic systems for antimicrobialsusceptibility testing, such as BD Phoenix, is arecently available instruments that makes it possible toobtain results within 12 h.Methods. Antimicrobial susceptibility testing resultsof the BD Phoenix system were compared to those obtainedfrom Clinical Laboratory Standards Institute (CLSI)disk-diffusion method. Two-hundred different clinicalisolates of streptococci were assayed: beta-hemolytic(n=65), viridans (n=87), S. penumoniae (n=48).Results. Overall, there was categorical agreement greaterthan 96.7% (94.8% for beta-hemolytic and 97.9% for viridansgroup) in relationship to the disk-diffusion method.The minor error rates were less than 10% for all the antibiotics.The greatest percentage of serious errors correspondedto erythromycin and clindamycin within the beta-hemolyticgroup (14.7%). Overall percentage of very serious errors wasless 0.5%. The results for penicillin in viridans streptococciand S. pneumoniae results showed 89.7% and 91.7% of categoricalagreement, respectively, using the Etest as reference.Conclusions. The automated BD Phoenix system is avery useful and effective diagnostic tool for quantitativetesting of sensitivity to antibiotics in the streptococci group (AU)

Enfermedad invasiva por Streptococcus pneumoniae: serotipos y sensibilidad a los antimicrobianos en un Área Sanitaria de Galicia / Invasive disease caused by Streptococcus pneumoniae: serotypes and antimicrobial susceptibility in a Health Care Area in Galicia

En el Área Sanitaria de Santiago de Compostela, durante un periodo de tres años (2004-2006) se estudiaron 218 cepas de Streptococcuspneumoniae productoras de enfermedad invasiva (10 LCR, 133 hemocultivos, 7 líquidos pleurales, 9 úlceras corneales y 59 de vías respiratoriasbajas), para conocer los serotipos predominantes y la sensibilidad antimicrobiana. Un 77,1% de las cepas procedían de adultos y un 22,9%de niños. Se encontraron 33 serotipos diferentes, seis de los cuales se aíslan con una frecuencia superior al 5%, y son, por orden decreciente,el 19 (16,97%), el 3 (11,46%), el 1 (10,55%), el 14 (10,55%), el 23 (6,88%) y el 6 (6,88%). En muestras de LCR predomina el serogrupo19 y en hemocultivos el 19, el 1, el 14 y el 3. De las 218 cepas, un 63,76% fueron sensibles a todos los antibióticos. Los fenotipos de no sensibilidadmás frecuentes fueron a la eritromicina (24,31%) y la penicilina (18,34%). Ambos fenotipos se asocian a los serotipos 19, 14 y 6. Lasensibilidad a la cefotaxima fue del 99,5%. La resistencia al levofloxacino fue del 0,9%. No hemos encontrado resistencias a la vancomicina(AU)

In the Health Care Area of Santiago de Compostela, during three years (2004-2006), we studied 218 Streptococcus pneumoniae isolates frominvasive disease (10 CSF, 133 blood culture, 7 pleural fluid, 9 corneal ulcer and 59 lower respiratory tract), to determine the predominantserotypes and antimicrobial susceptibility. 77.1% of the isolates were from adults and 22.9% from pediatric patients. There were 33 differentserotypes, six of them occurring in more than 5% of cases, in decreasing order: 19 (16.97%), 3 (11.46%), 1 (10.55%), 14 (10.55%), 23(6.88%) and 6 (6.88%). The predominant serogroup in CSF was 19 and in blood culture predominant serogroups were 19, 1, 14 and 3.63.76% of the isolates were susceptible to all antibiotics tested. The most frequent resistance phenotypes were to erythromycin (24.31%),followed by penicillin (18.34%). Both phenotypes were associated with serotypes 19, 14 and 6. The resistance to levofloxacin was 0.9% and0.5% to cefotaxime. We did not find any vancomycin resistance(AU)