Complex pathogens in infective endocarditis

Endocarditis; Diagnosis; TreatmentEndocarditis; Diagnóstico; TratamientoEndocarditis; Diagnòstic; TractamentInfective endocarditis (IE) is a complex disease whose prognosis depends on the causative microorganism, among other factors. The latter can be difficult to identify and/or treat. In this narrative review, we identify knowledge gaps in the diagnosis and antimicrobial treatment of IE, and attempt to shed light on current questions. Specifically, we: (1) analyze the factors that may hinder the microbiological diagnosis of blood culture-negative IE, as well as the role of new imaging techniques, such as 18F-fluorodeoxyglucose ([18F]FDG PET/CT), in the diagnostic capacity of this disease, understanding their advantages and assuming their limitations; (2) discuss the therapeutic approach to various difficult-to-treat microorganisms. In particular, we focus on the treatment of staphylococcal IE since, at present, staphylococci are the most frequent cause of IE in developed countries and staphylococcal IE is one of those with the highest short- and long-term mortality. We critically evaluate the current evidence on combination therapy and address the occurrence of serious side effects, an aspect that is often overlooked owing to the severity of the infection; and (3) emphasize the need for home antimicrobial treatment of patients with IE, as these are fragile people who benefit from an early return to their environment. This poses undoubted logistical challenges and requires robust evidence to ensure the best short- and long-term outcomes.Laura Escolà-Vergé has a Juan Rodés contract in the call 2020 Strategic Action Health from the Instituto de Salud Carlos III of Spanish Health Ministry for the years 2021-2024. This research was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea - NextGenerationEU

Clinical Features and Outcomes of Streptococcus anginosus Group Infective Endocarditis: A Multicenter Matched Cohort Study

Streptococcus anginosus; Endocarditis infecciosa; Estreptococs del grup viridansStreptococcus anginosus; Endocarditis infecciosa; Estreptococos del grupo viridansStreptococcus anginosus; Infective endocarditis; Viridans group streptococciBackground Although Streptococcus anginosus group (SAG) endocarditis is considered a severe disease associated with abscess formation and embolic events, there is limited evidence to support this assumption. Methods We performed a retrospective analysis of prospectively collected data from consecutive patients with definite SAG endocarditis in 28 centers in Spain and Italy. A comparison between cases due to SAG endocarditis and viridans group streptococci (VGS) or Streptococcus gallolyticus group (SGG) was performed in a 1:2 matched analysis. Results Of 5336 consecutive cases of definite endocarditis, 72 (1.4%) were due to SAG and matched with 144 cases due to VGS/SGG. SAG endocarditis was community acquired in 64 (88.9%) cases and affected aortic native valve in 29 (40.3%). When comparing SAG and VGS/SGG endocarditis, no significant differences were found in septic shock (8.3% vs 3.5%, P = .116); valve disorder, including perforation (22.2% vs 18.1%, P = .584), pseudoaneurysm (16.7% vs 8.3%, P = .108), or prosthesis dehiscence (1.4% vs 6.3%, P = .170); paravalvular complications, including abscess (25% vs 18.8%, P = .264) and intracardiac fistula (5.6% vs 3.5%, P = .485); heart failure (34.7% vs 38.9%, P = .655); or embolic events (41.7% vs 32.6%, P = .248). Indications for surgery (70.8% vs 70.8%; P = 1) and mortality (13.9% vs 16.7%; P = .741) were similar between groups. Conclusions SAG endocarditis is an infrequent but serious condition that presents a prognosis similar to that of VGS/SGG.This work was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005), co‐financed by the European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligent Growth 2014–2020. We thank CERCA Programme/Generalitat de Catalunya for institutional support. J. M. M. received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–2021

Clinical features and outcomes of Streptococcus anginosus group infective Endocarditis: a multicenter matched cohort study

[EN] Background. Although Streptococcus anginosus group (SAG) endocarditis is considered a severe disease associated with abscess formation and embolic events, there is limited evidence to support this assumption. Methods. We performed a retrospective analysis of prospectively collected data from consecutive patients with definite SAG endocarditis in 28 centers in Spain and Italy. A comparison between cases due to SAG endocarditis and viridans group streptococci (VGS) or Streptococcus gallolyticus group (SGG) was performed in a 1:2 matched analysis. Results. Of 5336 consecutive cases of definite endocarditis, 72 (1.4%) were due to SAG and matched with 144 cases due to VGS/ SGG. SAG endocarditis was community acquired in 64 (88.9%) cases and affected aortic native valve in 29 (40.3%). When comparing SAG and VGS/SGG endocarditis, no significant differences were found in septic shock (8.3% vs 3.5%, P = .116); valve disorder, including perforation (22.2% vs 18.1%, P = .584), pseudoaneurysm (16.7% vs 8.3%, P = .108), or prosthesis dehiscence (1.4% vs 6.3%, P = .170); paravalvular complications, including abscess (25% vs 18.8%, P = .264) and intracardiac fistula (5.6% vs 3.5%, P = .485); heart failure (34.7% vs 38.9%, P = .655); or embolic events (41.7% vs 32.6%, P = .248). Indications for surgery (70.8% vs 70.8%; P = 1) and mortality (13.9% vs 16.7%; P = .741) were similar between groups. Conclusions. SAG endocarditis is an infrequent but serious condition that presents a prognosis similar to that of VGS/SGG.This work was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005), co‐financed by the European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligent Growth 2014–2020. We thank CERCA Programme/Generalitat de Catalunya for institutional support. J. M. M. received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–2021

Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts

[Background] Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia.[Methods] A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3).[Results] Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03–6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04–4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12–0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08–4.24, p = 0.02).[Conclusions] Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.This study was funded by a research grant from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III [FIS PI15/00744], European Regional Development Fund (ERDF); CGV is a recipient of an INTENSIFICACIÓ Grant from the “Strategic plan for research and innovation in health-PERIS 2016-2020” and forms part of the Fungi CLINIC Research group (AGAUR-Project 2017SGR1432 of the Catalan Health Agency)

Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03–6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04–4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12–0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08–4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms

Long-term antibiotic therapy in patients with surgery-indicated not undergoing surgery infective endocarditis

Background: To date, there is little information regarding management of patients with infective endocarditis (IE) that did not undergo an indicated surgery. Therefore, we aimed to evaluate prognosis of these patients treated with a long-term antibiotic treatment strategy, including oral long term suppressive antibiotic treatment in five referral centres with a multidisciplinary endocarditis team.Methods: This retrospective, multicenter study retrieved individual patient-level data from five referral centres in Spain. Among a total of 1797, 32 consecutive patients with IE were examined (median age 72 years; 78% males) who had not undergone an indicated surgery, but received long-term antibiotic treatment (LTAT) and were followed by a multidisciplinary endocarditis team, between 2011 and 2019. Primary outcomes were infection relapse and mortality during follow-up.Results: Among 32 patients, 21 had IE associated with prostheses. Of the latter, 8 had an ascending aorta prosthetic graft. In 24 patients, a switch to long-term oral suppressive antibiotic treatment (LOSAT) was considered. The median duration of LOSAT was 277 days. Four patients experienced a relapse during follow-up. One patient died within 60 days, and 12 patients died between 60 days and 3 years. However, only 4 deaths were related to IE.Conclusions: The present study results suggest that a LTAT strategy, including LOSAT, might be considered for patients with IE that cannot undergo an indicated surgery. After hospitalization, they should be followed by a multidisciplinary endocarditis team

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections

Estado actual de la endocarditis enterocócica. Retos de futuro

L’objectiu d’aquesta tesi doctoral és avaluar l’epidemiologia, la clínica, les possibles portes d’entrada, el tractament i el pronòstic de l’endocarditis enterocòcica. Per aconseguir aquest objectiu s’han realitzat tres treballs. El primer partia de la hipòtesi que l’endocarditis infecciosa per Enterococcus faecalis (EIEF) ha experimentat canvis epidemiològics i clínics en els darrers anys. Es van estudiar tots els pacients adults amb EI definitiva tractats en el nostre centre (l’Hospital Vall d’Hebron) entre el 2007 i el 2018, un total de 648 episodis recollits prospectivament, evidenciant-se un augment en el percentatge anual de pacients amb EIEF (15% [2007] versus 25,3% [2018], p=0,038). Entre els 108 pacients amb EIEF, els de l’últim període (2015-2018, n=56) tenien una edat superior, es va identificar amb més freqüència un origen abdominal de la infecció, tenien menys indicació de cirurgia i, de forma no significativa, una mortalitat hospitalària inferior. A més, es va objectivar un augment en el percentatge d’ecocardiografies realitzades en els pacients amb bacterièmia monomicrobiana per E. faecalis (30% [2010] versus 51,2% [2018], p=0,014) i del percentatge d’EIEF en aquests pacients (15% [2010] versus 32,6% [2018], p=0,004). Es podria concloure que E. faecalis és una causa freqüent i en augment d’EI, probablement per una major realització d’ecocardiografies, entre d’altres causes. La hipòtesi del segon treball era que els pacients amb EIEF presenten una alta prevalença de lesions colorectals que poden ser la porta d’entrada d’una bacterièmia. Es va realitzar un estudi observacional i retrospectiu en quatre hospitals. Des del moment en que es va protocol·litzar en cada centre la realització d’una colonoscòpia en l’EIEF fins octubre del 2018, es van incloure tots els episodis consecutius d’EIEF definitiva en adults. Es van recollir les troballes endoscòpiques potencialment causants d’una bacterièmia. De 103 episodis, l’origen de la infecció era desconegut en 63 (61%) casos i presumptament conegut en els restants. En 78 (76%) es va realitzar una colonoscòpia i 47 (60%) tenien troballes endoscòpiques rellevants: 39 una malaltia neoplàsica i 8 no neoplàsica. El 64% dels pacients amb origen desconegut de la infecció i el 44% amb origen conegut tenien troballes endoscòpiques valorables. En conseqüència, realitzar una colonoscòpia en l’EIEF, independentment del suposat origen de la infecció, ajudaria a diagnosticar i tractar una probable malaltia colorectal i evitar noves bacterièmies. Finalment, el tercer treball va consistir en estudiar si la teicoplanina en monoteràpia és efectiva i segura pel tractament de l’endocarditis enterocòcica. Es va realitzar un anàlisi retrospectiu de la cohort prospectiva de pacients amb endocarditis enterocòcica definitiva tractats amb teicoplanina al nostre centre (2000-2017). Es va analitzar la mortalitat durant el tractament, les recidives i els efectes adversos. Vint-i-dos pacients van rebre teicoplanina, 9 (41%) com primera línia de tractament (8 episodis per E. faecium i 1 per E. faecalis) i 13 (59%) com segona (tots per E. faecalis). Els supervivents van rebre teicoplanina durant 27 dies de mediana (rang interquartílic 17-41,5), a una dosi de 10 (10-10,8) mg/kg/dia. Els motius per utilitzar la teicoplanina van ser: resistència a betalactàmics (41%), efectes adversos amb altres tractaments (32%) i facilitar el tractament antimicrobià parenteral ambulatori (TAPA) (27%). Es va retirar en 2 (9%) pacients per efectes adversos, cinc (23%) van morir i no hi va haver recidives amb un seguiment de 43,2 (22,1-69,1) mesos. Es podria considerar la teicoplanina com un tractament alternatiu en la endocarditis per E. faecium sensible i un tractament de seqüenciació en casos seleccionats d’EIEF quan apareixen efectes adversos o per realitzar TAPA.El objetivo de esta tesis doctoral es evaluar la epidemiología, la clínica, las posibles puertas de entrada, el tratamiento y el pronóstico de la endocarditis enterocócica. Para alcanzar dicho objetivo se han realizado tres trabajos. El primero partía de la hipótesis que la endocarditis infecciosa por Enterococcus faecalis (EIEF) ha experimentado cambios epidemiológicos y clínicos en los últimos años. Se estudiaron los datos de todos los pacientes adultos con EI definitiva tratados en nuestro centro (el Hospital Vall d’Hebron, Barcelona) entre el 2007 y el 2018, un total de 648 episodios recogidos prospectivamente, evidenciándose un aumento en el porcentaje anual de la EIEF (15% [2007] versus 25,3% [2018], p=0,038). Entre los 108 pacientes con EIEF, los del último periodo (2015-2018, n=56) tenían mayor edad, se identificó con mayor frecuencia un origen abdominal de la infección, tenían menor indicación de cirugía y, de forma no significativa, una mortalidad hospitalaria inferior. Asimismo, se objetivó un aumento del porcentaje de ecocardiografías realizadas en los pacientes con bacteriemia monomicrobiana por E. faecalis (30% [2010] versus 51,2% [2018], p=0,014) y del porcentaje de EIEF en estos pacientes (15% [2010] versus 32,6% [2018], p=0,004). Se podría concluir que E. faecalis es una causa frecuente y en aumento de EI, probablemente por una mayor realización de ecocardiografías, entre otras causas. La hipótesis del segundo trabajo era que los pacientes con EIEF presentan una alta prevalencia de lesiones colorrectales que pueden ser la puerta de entrada de una bacteriemia. Para analizarlo, se realizó un estudio observacional y retrospectivo en cuatro hospitales. Desde el momento en que se protocolizó en cada centro la realización de una colonoscopia en la EIEF hasta octubre del 2018, se incluyeron todos los episodios consecutivos de EIEF definitiva en adultos. Se recogieron los hallazgos endoscópicos potencialmente causantes de una bacteriemia. De 103 episodios, el origen de la infección fue desconocido en 63 (61%) casos y presuntamente conocido en los restantes. En 78 (76%) pacientes se realizó una colonoscopia y 47 (60%) tenían hallazgos endoscópicos relevantes: 39 una enfermedad colorrectal neoplásica y 8 no neoplásica. El 64% de los pacientes con origen de la infección desconocido y el 44% con origen conocido tenían hallazgos endoscópicos valorables. Por consiguiente, realizar una colonoscopia en la EIEF, independientemente del supuesto origen de la infección, ayudaría a diagnosticar y tratar una probable enfermedad colorrectal y evitar nuevas bacteriemias. Finalmente, el tercer trabajo consistió en estudiar si la teicoplanina en monoterapia es efectiva y segura para el tratamiento de la endocarditis enterocócica. Se realizó un análisis retrospectivo de la cohorte prospectiva de pacientes con endocarditis enterocócica definitiva tratados con teicoplanina en nuestro centro (2000-2017). Se analizó la mortalidad durante el tratamiento, las recidivas y los efectos adversos. Veintidós pacientes recibieron teicoplanina, 9 (41%) como primera línea de tratamiento (8 episodios por E. faecium y 1 por E. faecalis) y 13 (59%) como segunda (todos por E. faecalis). Los supervivientes recibieron teicoplanina durante 27 días de mediana (rango intercuartílico 17–41,5), a una dosis de 10 (10–10,8) mg/kg/día. Los motivos para usar la teicoplanina fueron la resistencia a betalactámicos (41%), los efectos adversos con otros tratamientos (32%) y facilitar el tratamiento antimicrobiano parenteral ambulatorio (TAPA) (27%). Se retiró en 2 (9%) pacientes por efectos adversos. Cinco (23%) fallecieron durante el tratamiento y no hubo recidivas con un seguimiento de 43,2 (22,1–69,1) meses. Se podría considerar la teicoplanina como un tratamiento alternativo en la endocarditis por E. faecium sensible y un tratamiento de secuenciación en casos seleccionados de EIEF cuando aparecen efectos adversos o para realizar TAPA.The objective of this doctoral thesis is to evaluate the epidemiology, the clinical manifestations, the portals of entry, the therapeutic options and the prognosis of enterococcal endocarditis. Three studies have been carried out for this purpose. The first study was based on the hypothesis that there have been relevant epidemiological and clinical changes in Enterococcus faecalis infective endocarditis (EFIE) in the last years. In this regard, all definitive IE episodes treated in our centre (Vall d’Hebron University Hospital, Barcelona) between 2007 and 2018 were analysed, a total of 648 episodes collected prospectively, and an annual increase in the percentage of EFIE was detected (15% [2007] versus 25.3% [2018], p=0.038). We studied 108 episodes of EFIE. Last period patients (2015-2018 n=56) were older, abdominal origin was established more frequently, they had less indication of surgery, and had a non-statistically significant lower in-hospital mortality. There was an increase in the percentage of echocardiograms performed in E. faecalis monomicrobial bacteraemia (30% [2010] versus 51.2% [2018], p=0.014), and in the percentage of EFIE diagnosed in these patients (15% [2010] versus 32.6% [2018], p=0.004). We may conclude that E. faecalis is a frequent and increasing cause of IE, probably linked to an increase in the percentage of echocardiograms performed, among other reasons. The hypothesis of the second study was that patients with EFIE have a high prevalence of colorectal lesions that may be the origin of the bacteraemia. To analyse this issue, an observational retrospective study was performed in four centres. From the moment that a colonoscopy was systematically performed in EFIE in each participating hospital until October 2018, we included all consecutive episodes of definite EFIE in adult patients. The outcome was an endoscopic finding of colorectal disease potentially causing bacteraemia. From 103 EFIE episodes, the presumed sources of infection were unknown in 63 (61%) and known in the remaining cases. Seventy-eight (76%) patients underwent a colonoscopy, and 47 (60%) had endoscopic findings: 39 (83%) had a colorectal neoplastic disease, and 8 (7%) a nonneoplastic disease. Relevant endoscopic findings were found in the 64% of the patients with an unknown portal of entry, and in the 44% with a known source of infection. Therefore, performing a colonoscopy in all EFIE patients, irrespective of the presumed source of infection, could be helpful to diagnose a probable colorectal disease in these patients and to avoid a new bacteraemia episode. Finally, the third study aimed to evaluate the effectiveness and safety of teicoplanin for treating enterococcal endocarditis. For this purpose, a retrospective analysis of a prospective cohort of definite EIE patients treated with teicoplanin in our centre (2000–2017) was performed. Outcomes were all-cause mortality during treatment, relapses and adverse effects. Twenty-two patients received teicoplanin, 9 (41%) as first-line therapy (8 episodes caused by Enterococcus faecium and 1 by Enterococcus faecalis) and 13 (59%) as continuation therapy (all caused by E. faecalis). The median duration of teicoplanin in survivors was 27 (interquartile range 17–41.5) days, at a dose of 10 (10–10.8) mg/kg/day. Reasons for teicoplanin use were beta-lactam resistance (41%), adverse effects with previous regimens (32%) and outpatient parenteral antimicrobial therapy (OPAT) (27%). Teicoplanin was withdrawn in 2 (9%) patients due to adverse effects. Five (23%) died during treatment, and there were no relapses with a median follow-up of 43.2 (22.1–69.1) months. In conclusion, teicoplanin could be used as alternative treatment for susceptible E. faecium IE and as continuation therapy in selected patients with EFIE when adverse events develop with standard regimens or to allow OPAT

Ceftolozane/tazobactam for the treatment of complicated intra-abdominal and urinary tract infections : Current perspectives and place in therapy

The current prevalence of infections caused by multidrug-resistant (MDR) organisms is a global threat, and thus, the development of new antimicrobial agents with activity against these pathogens is a healthcare priority. Ceftolozane-tazobactam (C/T) is a new combination of a cephalosporin with a β-lactamase inhibitor that shows excellent in vitro activity against a broad spectrum of Enterobacteriaceae and Pseudomonas aeruginosa, including extended spectrum β-lactamase-producing (ESBL) strains and MDR or extensively drug-resistant (XDR) P. aeruginosa. In phase III randomized clinical trials, C/T demonstrated similar efficacy to meropenem for the treatment of complicated intra-abdominal infections (cIAIs) and superior efficacy to levofloxacin for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. The drug is generally safe and well tolerated and its PK/PD profile is very favorable. Observational studies with C/T have revealed good efficacy for the treatment of different types of infection caused by MDR or XDR P. aeruginosa, including some that originated from the digestive or urinary tracts. The place of C/T in therapy is not well defined, but its use could be recommended in a carbapenem-sparing approach for the treatment of infections caused by ESBL-producing strains or for the treatment of infections caused by P. aeruginosa if there are no other more favorable therapeutic options. Further clinical experience is needed to position this new antimicrobial drug for the empirical treatment of cIAIs or cUTIs