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

Tractament amb ceftolozane-tazobactam; Infeccions intra-abdominals; Infeccions del tracte superior urinari; Pseudomonas aeruginosa resistentent a medicamentsTratamiento con ceftolozane-tazobactam; Infecciones intraabdominales; Infecciones del tracto superior urinario; Pseudomonas aeruginosa resistentes a medicamentosCeftolozane-tazobactam; Complicated intra-abdominal infections; Complicated urinary tract infections; Multidrug-resistant pseudomonas aeruginosaThe 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.The authors are funded by the Plan Nacional de I+D+I 2013-2016 and the Instituto de Salud Carlos III, Spain [REIPI RD16/0016/0003

Candida Periprosthetic Joint Infection: Is It Curable?

Fong; Infecció articular periprotèsica; Cirurgia d'intercanvi en dues etapesHongo; Infección de la articulación periprotésica; Cirugía de recambio en dos etapasFungus; Periprosthetic joint infection; Two-stage exchange surgeryCandida periprosthetic joint infection (CPJI) is a rare and very difficult to treat infection, and high-quality evidence regarding the best management is scarce. Candida spp. adhere to medical devices and grow forming biofilms, which contribute to the persistence and relapse of this infection. Typically, CPJI presents as a chronic infection in a patient with multiple previous surgeries and long courses of antibiotic therapy. In a retrospective series of cases, the surgical approach with higher rates of success consists of a two-stage exchange surgery, but the best antifungal treatment and duration of antifungal treatment are still unclear, and the efficacy of using an antifungal agent-loaded cement spacer is still controversial. Until more evidence is available, focusing on prevention and identifying patients at risk of CPJI seems more than reasonable.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors

Osteomielitis vertebral hematógena relacionada con la asistencia sanitaria : Características epidemiológicas, clínicas y evolución

Se trata de un estudio retrospectivo de los factores predisponentes, etiología, clínica, diagnóstico y evolución de las osteomielitis vertebrales hematógenas (OVH) relacionadas con la asistencia sanitaria (OVHAS) en pacientes adultos diagnosticados en el Hospital Valle de Hebrón durante el periodo comprendido entre 1987 y 2011, y posterior comparación con las de origen comunitario. Como principales conclusiones, un tercio de las OVH están relacionadas con la asistencia sanitaria, y un tercio se asocian a infección de catéter. Los pacientes con OVHAS tienen más patología subyacente, foco conocido de la infección, y peor evolución en cuanto a mortalidad y recidiva.Es tracta d'un estudi retrospectiu dels factors predisponents, etiologia, clínica, diagnòstic I evolució de les osteomielitis vertebrals hematògenes (OVH) relacionades amb l'assistència sanitària (OVHAS) en pacients adults diagnosticats a l'Hospital Vall d'Hebron durant el periode comprès entre 1987 i 2011, i posterior comparació amb les d'origen comunitari. Com a principals conclusions, un terç de les OVH están relacionades amb l'assistència sanitària, i un terç s'associen a infecció de catéter. Els pacients amb OVHAS tenen més patologia subjacent, focus conegut d'infecció, i pitjor evolució pel que fa a mortalitat i recidiva

Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial

Bacteremia; Daptomycin; FosfomycinBacterièmia; Daptomicina; FosfomicinaBacteriemia; Daptomicina; FosfomicinaBackground We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. Methods A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. Results Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93–1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). Conclusions Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events.This work was supported by the Spanish Ministry of Science, Innovation and Universities (PI12/01907); Spanish Network for Research in Infectious Diseases (RD16/0016/0005); Instituto de Salud Carlos III (ISCIII); and Spanish Ministry of Economy, Industry and Competitiveness. This work was also supported by the European Development Regional Fund “A way to achieve Europe,” Operational Programme Intelligent Growth 2014–2020; Spanish Clinical Research Network (SCReN), co-financed by the Plan Nacional de I+D and ISCIII, Subdirección General de Evaluación y Fomento de la Investigación (PT13/0002/0007); and the Grupo de Estudio de la Infección Relacionada con la Asistencia Sanitaria. J. M.-M. received a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques Agust Pi i Sunyer, Barcelona, Spain, during 2017–2021

Periprosthetic Joint Infection Prophylaxis in the Elderly after Hip Hemiarthroplasty in Proximal Femur Fractures: Insights and Challenges

Profilaxi antibiòtica; Hemiartroplàstia de maluc; Infecció periprotèsica de l'articulacióProfilaxis antibiótica; Hemiartroplastia de cadera; Infección de la articulación periprotésicaAntibiotic prophylaxis; Hip hemiarthroplasty; Periprosthetic joint infectionWe review antibiotic and other prophylactic measures to prevent periprosthetic joint infection (PJI) after hip hemiarthroplasty (HHA) surgery in proximal femoral fractures (PFFs). In the absence of specific guidelines, those applied to these individuals are general prophylaxis guidelines. Cefazolin is the most widely used agent and is replaced by clindamycin or a glycopeptide in beta-lactam allergies. A personalized antibiotic scheme may be considered when colonization by a multidrug-resistant microorganism (MDRO) is suspected. Particularly in methicillin-resistant Staphylococcus aureus (MRSA) colonization or a high prevalence of MRSA-caused PJIs a glycopeptide with cefazolin is recommended. Strategies such as cutaneous decolonization of MDROs, mainly MRSA, or preoperative asymptomatic bacteriuria treatment have also been addressed with debatable results. Some areas of research are early detection protocols in MDRO colonizations by polymerase-chain-reaction (PCR), the use of alternative antimicrobial prophylaxis, and antibiotic-impregnated bone cement in HHA. Given that published evidence addressing PJI prophylactic strategies in PFFs requiring HHA is scarce, PJIs can be reduced by combining different prevention strategies after identifying individuals who will benefit from personalized prophylaxis.This work was supported by the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, through the project PI15/02161 and by the Plan Nacional de I+D+i 2013-016 and ISCIIII, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003)-co-financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020

Risk Factors for Relapse in Acute Bacterial Prostatitis: the Impact of Antibiotic Regimens

Acute bacterial prostatitis; Antibiotic resistance; RelapseProstatitis bacteriana aguda; Resistencia a los antibióticos; RecaídaProstatitis bacteriana aguda; Resistència als antibiòtics; RecaigudaThe aim of the study was to analyze the risk factors for relapse in patients with acute bacterial prostatitis (ABP), focusing on the impact of different antibiotic regimens. We conducted an observational study of all patients diagnosed with ABP (irritative and/or obstructive urinary symptoms, temperature of >37.8°C, and the presence of bacteriuria in urine culture, in the absence of data suggesting pyelonephritis) from January 2017 to December 2018. The main outcome was relapse. We performed a multivariate analysis to identify the risk factors associated with relapse. A propensity score with inverse weighting was applied to attenuate antibiotic selection bias. We included 410 patients. The mean age was 68 years; 28.8% had diabetes mellitus, and 61.1% benign prostatic hyperplasia. The most common isolated bacteria were Escherichia coli (62.4%) and Klebsiella spp. (10%). The overall resistance rate was 39.5% to quinolones. The mortality rate was 1.2%, and the relapse rate was 6.3%. The only independent risk factor for relapse was inadequate antibiotic therapy (odds ratio [OR] 12.3; 95% confidence interval [95% CI], 3.5 to 43.1). When the antibiotic was modified according to the susceptibility pattern, the rates of relapse were 1.8% in those treated with ciprofloxacin, 3.6% with intravenous beta-lactam, 9.3% with co-trimoxazole, and 9.8% with oral (p.o.) beta-lactam (P = 0.03). Treatment with oral beta-lactam (OR, 5.3; 95% CI, 1.2 to 23.3) and co-trimoxazole (OR, 4.9; 95% CI, 1.1 to 23.2) were associated with a risk of relapse. In this large real-life observational study, a significantly higher relapse rate was observed when antibiotic treatment was inadequate. When the antibiotic was tailored, quinolones and intravenous beta-lactams had a lower relapse rate than co-trimoxazole and oral beta-lactams. IMPORTANCE In the manuscript, we report a large series of acute bacterial prostatitis cases and describe data about the etiology, antibiotic resistance rate, and outcome, specially focused on the risk factors for relapse. We found high rates of resistance to the most frequently used antibiotics and a high relapse rate in patients whose treatment was not adjusted according to their microbiological susceptibility. We did not observe differences, though, in mortality or relapse according to appropriate or inappropriate empirical treatment. What is new in this article is the different relapse rates observed depending upon the definitive adequate antibiotic used. Quinolones and intravenous (i.v.) beta-lactam have lower rates of relapse (1.8% and 3.6%, respectively) compared to co-trimoxazole and oral (p.o.) beta-lactam (3.3% and 9.8%, respectively). Clinicians should carefully choose an adequate antibiotic for definitive ABP treatment depending on the results of microbiological isolation, using quinolones as the first option. Whenever quinolones cannot be administered, i.v. beta-lactams seem to be the second-best option.The Spanish Network for Research in Infectious Diseases is supported by AGAUR grant 2017 SGR 1055, Generalitat de Catalunya. No other financial support was received for this work

Red flags for the early detection of spinal infection in back pain patients

© 2019 The Author(s). Background: Red flags are signs and symptoms that are possible indicators of serious spinal pathology. There is limited evidence or guidance on how red flags should be used in practice. Due to the lack of robust evidence for many red flags their use has been questioned. The aim was to conduct a systematic review specifically reporting on studies that evaluated the diagnostic accuracy of red flags for Spinal Infection in patients with low back pain. Methods: Searches were carried out to identify the literature from inception to March 2019. The databases searched were Medline, CINHAL Plus, Web of Science, Embase, Cochrane, Pedro, OpenGrey and Grey Literature Report. Two reviewers screened article texts, one reviewer extracted data and details of each study, a second reviewer independently checked a random sample of the data extracted. Results: Forty papers met the eligibility criteria. A total of 2224 cases of spinal infection were identified, of which 1385 (62%) were men and 773 (38%) were women mean age of 55 (± 8) years. In total there were 46 items, 23 determinants and 23 clinical features. Spinal pain (72%) and fever (55%) were the most common clinical features, Diabetes (18%) and IV drug use (9%) were the most occurring determinants. MRI was the most used radiological test and Staphylococcus aureus (27%), Mycobacterium tuberculosis (12%) were the most common microorganisms detected in cases. Conclusion: The current evidence surrounding red flags for spinal infection remains small, it was not possible to assess the diagnostic accuracy of red flags for spinal infection, as such, a descriptive review reporting the characteristics of those presenting with spinal infection was carried out. In our review, spinal infection was common in those who had conditions associated with immunosuppression. Additionally, the most frequently reported clinical feature was the classic triad of spinal pain, fever and neurological dysfunction. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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