Efficacy and safety of colistin plus beta-lactams for bone and joint infection caused by fluoroquinolone-resistant gram-negative bacilli: a prospective multicenter study.

OBJECTIVES: The prognosis of bone and joint infections (BJI) caused by Gram-negative bacilli (GNB) worsens significantly in the face of fluoroquinolone-resistance. In this setting, scarce pre-clinical and clinical reports suggest that intravenous beta-lactams plus colistin may improve outcome. Our aim was to assess the efficacy and safety of this treatment in a well-characterized prospective cohort. METHODS: Observational, prospective, non-comparative, multicenter (14 hospitals) study of adults with BJI caused by fluoroquinolone-resistant GNB treated with surgery and intravenous beta-lactams plus colistin for ≥ 21 days. The primary endpoint was the cure rate. RESULTS: Of the 44 cases included (median age 72 years [IQR 50-81], 22 [50%] women), 32 (73%) had an orthopedic device-related infection, including 17 (39%) prosthetic joints. Enterobacterales were responsible for 27 (61%) episodes, and Pseudomonas spp for 17 (39%), with an overall rate of MDR/XDR GNB infections of 27/44 (61%). Patients were treated with colistin plus intravenous beta-lactam for 28 days (IQR 22-37), followed by intravenous beta-lactam alone for 19 days (IQR 5-35). The cure rate (intention-to-treat analysis; median follow-up = 24 months, IQR 19-30) was 82% (95% CI 68%-90%) and particularly, 80% (95% CI 55%-93%) among patients managed with implant retention. Adverse events (AEs) leading to antimicrobial withdrawal occurred in 10 (23%) cases, all of which were reversible. Colistin AEs were associated with higher plasma drug concentrations (2.8 mg/L vs. 0.9 mg/L, p = 0.0001). CONCLUSIONS: Combination therapy with intravenous beta-lactams plus colistin is an effective regimen for BJI caused by fluoroquinolone-resistant GNB. AEs were reversible and potentially preventable by close therapeutic drug monitoring.

Determining the usefulness of systematic 18F-FDG PET/CT for the management of invasive fungal infection (PETIFI project): a prospective national multicentre cohort study protocol.

INTRODUCTION: The evaluation of staging and activity of invasive fungal infection (IFI) is used to adjust the type and duration of antifungal therapy (AT). Typically anatomy-based imaging is used. Positron emission tomography/CT with 18F-fluorodeoxyglucose (18F-FDG PET/CT) not only evaluates more than one body area in one session, but adds functional information to the anatomic data provided by usual imaging techniques and can potentially improve staging of IFI and monitoring of the response to therapy. Our objective is to analyse the impact of the systematic use of 18F-FDG PET/CT in IFI diagnostic and therapeutic management. METHODS AND ANALYSIS: Multicentre prospective cohort study of IFI with performance of systematic 18F-FDG PET/CT at diagnosis and follow-up that will be carried out in 14 Spanish tertiary hospitals. It is planned to include 224 patients with IFI over a 2-year study period. Findings and changes in management before and after 18F-FDG PET/CT will be compared. Additionally, the association of initial quantitative 18F-FDG PET/CT parameters with response to therapy will be evaluated.The primary endpoint is to compare the yield of 18F-FDG PET/CT with standard management without 18F-FDG PET/CT in IFI at initial assessment (staging) and in monitoring the response to treatment.The impact of the results of 18F-FDG PET/CT on the diagnostic-therapeutic management of patients with IFI (added value), as well as the prognostic ability of different quantification parameters of 18F-FDG PET/CT will be secondary endpoints. ETHICS AND DISSEMINATION: The Clinical Research Ethics Committee of Puerta de Hierro-Majadahonda University Hospital approved the protocol of the study at the primary site. We plan to publish the results in high-impact journals. TRIAL REGISTRATION NUMBER: NCT05688592.

Cutibacterium spp. Infections after Instrumented Spine Surgery Have a Good Prognosis Regardless of Rifampin Use: A Cross-Sectional Study.

Infection after spinal instrumentation (IASI) by Cutibacterium spp. is being more frequently reported. The aim of this study was to analyse the incidence, risk factors, clinical characteristics, and outcome of a Cutibacterium spp. IASI (CG) compared with non-Cutibacterium IASI (NCG) infections, with an additional focus on the role of rifampin in the treatment. All patients from a multicentre, retrospective, observational study with a confirmed IASI between January 2010 and December 2016 were divided into two groups: (CG and NCG) IASI. Baseline, medical, surgical, infection treatment, and follow-up data were compared for both groups. In total, 411 patients were included: 27 CG and 384 NCG. The CG patients were significantly younger. They had a longer median time to diagnosis (23 vs. 13 days) (p = 0.025), although 55.6% debuted within the first month after surgery. Cutibacterium patients were more likely to have the implant removed (29.6% vs. 12.8%; p = 0.014) and received shorter antibiotic regimens (p = 0.014). In 33% of Cutibacterium cases, rifampin was added to the baseline therapy. None of the 27 infections resulted in treatment failure during follow-up regardless of rifampin use. Cutibacterium spp. is associated with a younger age and may cause both early and late IASIs. In our experience, the use of rifampin to improve the outcome in the treatment of a Cutibacterium spp. IASI is not relevant since, in our series, none of the cases had therapeutic failure regardless of the use of rifampin.

Effective definition of low humoral response to Clostridioides difficile infection.

BACKGROUND: Determination of the humoral response to Clostridioides difficile (CD) toxins could be of great value in the management of patients with CD infection (CDI). METHODS: A prospective study was conducted on the clinical characteristics and humoral response in patients with CDI. Determination of ELISA IgG CD anti-toxin B (tgcBiomics, Germany) was performed. The following dilutions were planned for each patient, 1:100, 1: 200, 1: 400, 1: 800: 1: 1600. A significant concentration of antibody was considered to be present in each dilution if an optical density 0.2 units higher than the negative control of the technique was evident. RESULTS: Eighty-five patients were included during the study period, November 2018-February 2020. The median age was 73 years (interquartile range: 62.5-85 years), with female predominance (45 patients, 52.9%). Thirty-nine patients (45.9%) had a severe infection. Seven patients (8.2%) had suffered an episode of CDI in the previous three months. Seventeen patients (20%) had one or more recurrent episodes during the three-month follow-up: No patient died during admission or required surgery for severe-complicated infection. The incidence of recurrence in patients with no antibody detected at 1:400 dilution was 25.4% (16 patients) while it was 4.3% (one patient) in patients with antibody present at that dilution (p = 0.03). Liver cirrhosis was associated with higher humoral response against CD. CONCLUSIONS: Antibodies IgG CD anti-toxin B detection at a dilution of 1:400, using a B ELISA technique, effectively identified patients at increased risk of recurrence. This information could help assist in the management of patients.

Thalamic abscess in a patient with hereditary hemorrhagic telangiectasia successfully treated with an empiric antibiotic regime: case report and review of the literature.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease associated with neurological complications, including cerebral abscesses (CA). They tend to be unique, supratentorial and lobar. While the surgical intervention is a rule of thumb when treating and diagnosing the etiology of these lesions, this is not always possible due to dangerous or inaccessible locations. We report the case of a patient solely treated with empiric antibiotics without stereotaxic intervention and satisfactory results. CASE PRESENTATION: We present the case of a 21-year-old patient with a right thalamic abscess due to HHT and pulmonary arteriovenous malformations, previously embolized, treated solely with antibiotics. At first, we contemplated the possibility of a stereotaxic biopsy, but the high-risk location and the fact that our patient received a previous full course of antibiotic treatment (in another center), made us discard this intervention because of the low diagnostic yield. We started an empiric antibiotic regime. We followed up very closely the clinical and radiological evaluation the next weeks, adjusting our antibiotic treatment when necessary. The results were favorable from both the radiological and clinical aspects and 6 months after the diagnosis the images show its almost complete disappearance. CONCLUSION: Carefully tailored antibiotic-only regime and vigilance of its adverse effects and close radiological following is a good treatment approach when surgery is not an option.

Implant Removal in the Management of Prosthetic Joint Infection by Staphylococcus aureus: Outcome and Predictors of Failure in a Large Retrospective Multicenter Study.

OBJECTIVES: To compare the characteristics and outcomes of cases with acute prosthetic joint infection (PJI; early post-surgical or hematogenous) by Staphylococcus aureus managed with implant removal (IRm) or debridement and retention (DAIR). To analyze the outcomes of all cases managed with IRm (initially or after DAIR failure). METHODS: Retrospective, multicenter, cohort study of PJI by S. aureus (2003-2010). Overall failure included mortality within 60 days since surgery and local failure due to staphylococcal persistence/relapse. RESULTS: 499 cases, 338 initially managed with DAIR, 161 with IRm. Mortality was higher in acute PJI managed initially with IRm compared to DAIR, but not associated with the surgical procedure, after propensity score matching. Underlying conditions, hemiarthroplasty, and methicillin-resistant S. aureus were risk factors for mortality. Finally, 249 cases underwent IRm (88 after DAIR failure); overall failure was 15.6%. Local failure (9.3%) was slightly higher in cases with several comorbidities, but independent of previous DAIR, type of IRm, and rifampin treatment. CONCLUSIONS: In a large multicenter study of S. aureus PJI managed with IRm, failure was low, but mortality significant, especially in cases with acute PJI and underlying conditions, but not associated with the IRm itself. Rifampin efficacy was limited in this setting.

Infections after spine instrumentation: effectiveness of short antibiotic treatment in a large multicentre cohort.

BACKGROUND AND OBJECTIVES: Available information about infection after spine instrumentation (IASI) and its management are scarce. We aimed to analyse DAIR (debridement, antibiotics and implant retention) prognosis and evaluate effectiveness of short antibiotic courses on early forms. METHODS: Multicentre retrospective study of patients with IASI managed surgically (January 2010-December 2016). Risk factors for failure were analysed by multivariate Cox regression and differences between short and long antibiotic treatment were evaluated with a propensity score-matched analysis. RESULTS: Of the 411 IASI cases, 300 (73%) presented in the first month after surgery, 48 in the second month, 22 in the third and 41 thereafter. Infections within the first 2 months (early cases) occurred mainly to older patients, with local inflammatory signs and predominance of Enterobacteriaceae, unlike those in the later periods. When managed with DAIR, prognosis of early cases was better than later ones (failure rate 10.4% versus 26.1%, respectively; P = 0.02). Risk factors for DAIR failure in early cases were female sex, Charlson Score, large fusions (>6 levels) and polymicrobial infections (adjusted HRs of 2.4, 1.3, 2.6 and 2.26, respectively). Propensity score matching proved shorter courses of antibiotics (4-6 weeks) as effective as longer courses (failure rates 11.4% and 10.5%, respectively; P = 0.870). CONCLUSIONS: IASIs within the first 2 months could be managed effectively with DAIR and shorter antibiotic courses. Clinicians should be cautious when faced with patients with comorbidities, large fusions and/or polymicrobial infections.

Risk Factors for Clostridium Difficile Diarrhea in Patients With Solid Organ Transplantation.

BACKGROUND: There is limited knowledge about specific risk factors for Clostridium difficile infection (CDI). METHOD: A retrospective study comparing cases of CDI in solid organ transplant (SOT) recipients with controls (SOT recipients who did not present CDI). RESULTS: Thirty patients with SOT from 1340 transplantation recipients had at least 1 episode of CDI (2.23%). The accumulated incidence was 3.06% in liver transplantation, 2.78% in lung transplantation, 2.36% in kidney transplantation, and 0.33% in heart transplantation. Seven (23%) cases occurred during the first 2 months. Fifteen (50%) cases were community acquired. Colonoscopy was performed in 6 (20%) cases, but pseudomembranes were observed in only 1 (16%) case. Independent variables found to be related to CDI were previous treatment with proton pump inhibitors (PPIs; odds ratio [OR] 5.5; 95% confidence interval [CI] 1.2-32.0), immunosuppressive regimen including mycophenolate (OR 5.2; 95%CI 1.1-18), hospitalization during the previous 3 months (OR 5.1; 95%CI 1.1-17), and antibiotic treatment during the previous month (OR 6.7; 95%CI 1.4-23). Five (16.7%) patients did not respond to the initial treatment. Recurrences were noted in 6 (20%) patients. CONCLUSIONS: Liver transplant recipients presented the highest incidence. Risk factors for CDI were previous treatment with PPIs, immunosuppressive regimen containing mycophenolate, prior hospitalization, and prior antibiotic treatment.

Gonococcal endocarditis: a case report and review of the literature.

A 59-year-old Caucasian male presented with progressive dyspnea, arthralgias and fever for three days. A diastolic regurgitation murmur was detected in the aortic area. A transesophageal echocardiograph showed several vegetations and severe aortic regurgitation. Blood cultures yielded Neisseria gonorrhoeae beta-lactamase negative. The patient had not noticed any urogenital discomfort or urethral discharge. The patient successfully underwent surgery for septal abscess debridement. The patient received ceftriaxone 2 g bid for eight weeks and the clinical follow-up was uneventful. The review of the literature revealed a total of the 38 additional cases reported between 1980 and the present. The majority of the patients were young, male and with native valve involvement. There has been a clear tendency for left-sided valve involvement (especially in the aortic valve). All valve cultures were reported negative despite, in most cases, the marked tissue destruction. Polymerase chain reaction was performed in two patients and positive results were shown in both. Cultures of exudates from other locations were negative in most cases. One striking fact is the high proportion of patients who underwent surgery (72 %). Information regarding antibiotic sensitivity was available in 28 cases, with penicillin resistance reported in six patients (21 %) and intermediate sensitivity in four patients (14 %). Resistance to ciprofloxacin was reported in two cases (7 %). A rapid increase and distribution of isolates resistant to third generation cephalosporins have been recently detected. The mortality is high, particularly taking into account that most were young patients who had not presented previous heart disease.

[Aetiology of surgical infections in patients undergoing craniotomy]. / Etiología de las infecciones quirúrgicas en pacientes sometidos a craneotomía.

BACKGROUND: Postoperative infections in patients undergoing craniotomy constitute significant complications associated with increased hospital stay and patient morbidity and mortality. Knowing the aetiology of surgical infections after craniotomy may contribute to improving antibiotic prophylaxis and empirical treatment. METHOD: Information relating to surgical infections in patients undergoing craniotomy was obtained from a series of annual surveys on prevalence of infections in Spanish hospitals (EPINE) during the period 1999-2006. The study protocol collected relevant clinical information on patients with infection. Presence of infection was determined according to the Centres for Disease Control infection criteria. RESULTS: During the time period considered, 107 cases of surgical infections in patients undergoing craniotomy were diagnosed. Forty patients were women (37%) and 67 were male (63%). The mean age was 51.7 years (median 55, range 6-86 years). The duration of the intervention was over 180minutes in 49 patients (45.8%).Thirty-eight patients (35.5%) underwent emergency surgery. Seventy-eight patients (73%) received surgical prophylaxis. Thirty-eight patients (35.5%) had superficial infection of the surgical wound, 38 patients (35.5%) had deep wound infection (including bone flap) and 31 patients (29%), postoperative infections of organ or space (meningitis, subdural empyema or brain abscess). The most common aetiology corresponded to staphylococci (50%), mainly S. aureus (one third of them methicillin-resistant), Pseudomonas aeruginosa (11%), Enterobacter spp (10%) and Acinetobacter baumannii (9%). CONCLUSION: Empirical treatment of these infections should include a glycopeptide such as vancomycin and a beta-lactam with coverage against non-fermenting gram-negative bacilli.

[Microbiology of surgical site infections in abdominal tract surgery patients]. / Microbiología de las infecciones del sitio quirúrgico en pacientes intervenidos del tracto digestivo.

INTRODUCTION: Knowledge of the microbiology of surgical infections after abdominal surgery can be of use when prescribing effective empirical antibiotic treatments. METHOD: Analysis of surgical infections after abdominal surgery in patients enrolled in the Prevalence of Infections in Spanish Hospitals (EPINE) corresponding to the years 1999-2006. RESULTS: During the period of the study, 2,280 patients who were subjected to upper or lower abdominal tract surgery were diagnosed with an infection at the surgical site (SSI). Eight hundred and eighty three patients (37%) had an operation of the upper abdominal tract (gastric, hepatobiliary, and pancreatic surgery) and 1,447 patients (63%) lower abdominal tract surgery (appendectomy and colon surgery). A total of 2,617 bacterial species were isolated in the 2,280 patients included in the analysis. The most frequent microorganisms isolated were, Escherichia coli (28%), Enterococcus spp. (15%), Streptococcus spp. (8%), Pseudomonas aeruginosa (7%), and Staphylococcus aureus (5%, resistant to methicillin 2%). In the surgical infections after upper abdominal tract procedures, there were a higher proportion of isolations of staphylococci, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter spp. and Candida albicans and less Escherichia coli, Bacteroides fragilis and Clostridium spp. CONCLUSION: The microbiology of SSI produced after upper abdominal tract surgery did not show any significant differences compared to those of the lower tract. However, more cases of SSI were detected due to staphylococci, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter spp. and Candida albicans and less caused by Escherichia coli, Bacteroides fragilis and Clostridium spp.

Preoperative low molecular weight heparin as venous thromboembolism prophylaxis in patients at risk for prosthetic infection after knee arthroplasty.

OBJECTIVE: To investigate the effect of preoperative initiation of low molecular weight heparin as prophylaxis for deep venous thrombosis in patients at risk of developing surgical-site infections after knee arthroplasty. DESIGN: Case-control study nested in a cohort. The incidence of surgical-site infection in the cohort was calculated. With the use of data extracted from medical histories and after adjustment for other risk factors, the effect of preoperative heparinization on the risk of incisional and prosthetic infection among case-patients and control-patients (1:3 ratio) was assessed. SETTING: Orthopedic department in a tertiary-care referral hospital. PATIENTS: A cohort of 160 consecutive patients who had received prosthetic knee implants between October 1, 2001, and November 30, 2003. RESULTS: Eighteen patients with surgical-site infections were identified, yielding an incidence of incisional and prosthetic infection of 6.9 (95% confidence interval [CI95], 3.5 to 12.0) and 4.4 (CI95, 1.8 to 8.8) cases per 100 patients undergoing surgery, respectively. Surgical-site infection was associated with preoperative use of low molecular weight heparin (odds ratio [OR], 6.2 after adjustment for medical and surgical factors; CI95 1.5 to 23). Prosthetic infection was strongly associated with preoperative use of prophylaxis (OR, undetermined [100% exposure in case-patients vs 35% exposure in control-patients]; P = .002), but incisional surgical-site infection was not. CONCLUSION: The use of low molecular weight heparins immediately before knee arthroplasty as prophylaxis for deep venous thrombosis should be questioned because of probable increased risk of prosthetic infection.