High Rate of Undetected Infections in Failed Osteosynthesis of Pertrochanteric Fractures.

OBJECTIVE: The objective of this study was to assess the incidence of infection in patients with cutout after proximal femur fracture (PFF) osteosynthesis. DESIGN: Retrospective cohort study. SETTING: Third-level trauma center. PATIENT SELECTION CRITERIA: Patients presenting with a cutout following PFF (OTA/AO 31A) osteosynthesis, between January 2007 and December 2020. OUTCOME MEASUREMENTS AND COMPARISONS: The primary outcome was infection according to the European Bone and Joint Infection Society criteria. RESULTS: Sixty-seven patients presenting with a cutout were included, with mean age of 83.3 years (range 63-96), and 51 (76.1%) were women. Of all cases, 16 (24.7%) presented a concomitant infection. The presence of concomitant infection was suspected preoperatively in only 3 of the cases. A subgroup analysis was performed between the cases with infection and those without infection, the groups being comparable in terms of demographic data and postoperative radiological criteria. Patients with underlying infection had a higher rate of surgical wound complication (56.3% vs. 22%, P = 0.014) and higher rates of leukocytosis (11.560 vs. 7.890, P = 0.023). CONCLUSION: Faced with a cutout after osteosynthesis of a PFF, underlying infection should be considered as a possible etiological factor. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Usefulness of Preoperative Determination of Serum MR-ProAdrenomedullin Levels to Predict the Need for Postoperative Organ Support in Abdominal Oncological Surgery.

The need for postoperative organic support is associated with patient outcomes. Biomarkers may be useful for detecting patients at risk. MR-ProADM is a novel biomarker with an interesting profile that can be used in this context. The main objective of this study was to verify whether there was an association between the preoperative serum levels of MR-ProADM and the need for organic support after elective abdominal cancer surgery, and to determine the preoperative MR-ProADM value that predicts the need for postoperative organic support. This was a multicenter prospective observational study conducted by four tertiary hospitals in Spain between 2017 and 2018. Plasma samples were collected for the quantification of MR-ProADM from adults who underwent major abdominal surgery during 2017-2018. The primary outcome was the need for organic support in the first seven postoperative days and its association with the preoperative levels of MR-ProADM, and the secondary outcome was the preoperative levels of MR-ProADM in the study population. This study included 370 patients with a mean age of 67.4 ± 12.9 years. Seventeen percent (63 patients) required some postoperative organic support measures in the first week. The mean preoperative value of MR-ProADM in patients who required organic support was 1.16 ± 1.15 nmol/L. The AUC-ROC of the preoperative MR-ProADM values associated with the need for organic support was 0.67 (95% CI: 0.59-0.75). The preoperative MR-ProADM value, which showed the best compromise in sensitivity and specificity for predicting the need for organic support, was 0.70 nmol/L. The negative predictive value was 91%. A multivariate analysis confirmed that a preoperative level of MR-ProADM ≥ 0.70 nmol/L is an independent factor associated with risk of postoperative organic support (OR 2, 6). Elevated preoperative MR-ProADM levels are associated with the need for postoperative organic support. Therefore, MR-ProADM may be a useful biomarker for perioperative risk assessment.

Critically ill patients with community-onset intraabdominal infections: Influence of healthcare exposure on resistance rates and mortality.

The concept of healthcare-associated infections (as opposed to hospital-acquired infections) in intraabdominal infections (IAIs) is scarcely supported by data in the literature. The aim of the present study was to analyse community-onset IAIs (non-postoperative/non-nosocomial) in patients admitted to intensive care units (ICUs), to investigate differences in resistance patterns linked to healthcare exposure and mortality-associated factors. A one-year prospective observational study (17 Spanish ICUs) was performed distributing cases as healthcare-associated infections (HCAI), community-acquired infections (CAI) and immunocompromised patients (ICP). Bacteria producing extended-spectrum ß-lactamases (ESBL) and/or carbapenemase (CPE), high-level aminoglycoside- and/or methicillin- and/or vancomycin- resistance were considered antimicrobial resistant (AMR). Mortality-associated factors were identified by regression multivariate analysis. Of 345 patients included (18.8% HCAI, 6.1% ICP, 75.1% CAI), 51.6% presented generalized peritonitis; 32.5% were >75 years (55.4% among HCAI). Overall, 11.0% cases presented AMR (7.0% ESBL- and/or CPE), being significantly higher in HCAI (35.4%) vs. CAI (5.8%) (p<0.001) vs. ICP (0%) (p = 0.003). Overall 30-day mortality was 14.5%: 23.1% for HCAI and 11.6% for CAI (p = 0.016). Mortality (R2 = 0.262, p = 0.021) was positively associated with age >75 years (OR = 6.67, 95%CI = 2.56-17.36,p<0.001), Candida isolation (OR = 3.05, 95%CI = 1.18-7.87,p = 0.022), and SAPS II (per-point, OR = 1.08, 95%CI = 1.05-1.11, p<0.001) and negatively with biliary infections (OR = 0.06, 95%CI = 0.01-0.48,p = 0.008). In this study, the antimicrobial susceptibility pattern of bacteria isolated from patients with healthcare contact was shifted to resistance, suggesting the need for consideration of the healthcare category (not including hospital-acquired infections) for severe IAIs. 30-day mortality was positively related with age >75 years, severity and Candida isolation but not with AMR.

Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients.

BACKGROUND: Dosing in obese critically ill patients is challenging due to pathophysiological changes derived from obesity and/or critical illness, and it remains fully unexplored. This study estimated the micafungin probability of reaching adequate 24-h area under the curve (AUC0-24h)/minimum inhibitory concentration (MIC) values against Candida spp. for an obese/nonobese, critically ill/noncritically ill, large population. METHODS: Blood samples for pharmacokinetic analyses were collected from 10 critically ill nonobese patients, 10 noncritically ill obese patients, and 11 critically ill morbidly obese patients under empirical/directed micafungin treatment. Patients received once daily 100-150 mg micafungin at the discretion of the treating physician following the prescribing information and hospital guidelines. Total micafungin concentrations were determined by high-performance liquid chromatography (HPLC). Monte-Carlo simulations were performed and the probability of target attainment (PTA) was calculated using the AUC0-24/MIC cut-offs 285 (C. parapsilosis), 3000 (all Candida spp.), and 5000 (nonparapsilosis Candida spp.). Intravenous once-daily 100-mg, 150-mg, and 200-mg doses were simulated at different body weights (45, 80, 115, 150, and 185 kg) and age (30, 50, 70 and 90 years old). PTAs ≥ 90% were considered optimal. Fractional target attainment (FTA) was calculated using published MIC distributions. A dosing regimen was considered successful if the FTA was ≥ 90%. RESULTS: Overall, 100 mg of micafungin was once-daily administered for nonobese and obese patients with body mass index (BMI) ≤ 45 kg/m2 and 150 mg for morbidly obese patients with BMI > 45 kg/m2 (except two noncritically ill obese patients with BMI ~ 35 kg/m2 receiving 150 mg, and one critically ill patient with BMI > 45 kg/m2 receiving 100 mg). Micafungin concentrations in plasma were best described using a two-compartment model. Weight and age (but not severity score) were significant covariates and improved the model. FTAs > 90% were obtained against C. albicans with the 200 mg/24 h dose for all body weights (up to 185 kg), and with the 150 mg/24 h for body weights < 115 kg, and against C. glabrata with the 200 mg/24 h dose for body weights < 115 kg. CONCLUSION: The lack of adequacy for the 100 mg/24 h dose suggested the need to increase the dose to 150 mg/24 h for C. albicans infections. Further pharmacokinetic/pharmacodynamic studies should address optimization of micafungin dosing for nonalbicans Candida infections.

Biomarkers (Procalcitonin, C Reactive Protein, and Lactate) as Predictors of Mortality in Surgical Patients with Complicated Intra-Abdominal Infection.

BACKGROUND: An accurate and readily available biomarker for identifying patients with complicated intra-abdominal infection needing special attention in critical care units because of their greater risk of dying would be of value for intensivists. METHODS: A multi-center, observational, retrospective study explored blood lactate, C-reactive protein (CRP), and procalcitonin (PCT) concentrations, and also Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS II) as mortality predictors in all adult patients with complicated intra-abdominal infection (cIAI) admitted to Surgical Critical Care Units (SCCUs) for ≥48 h in four Spanish hospitals (June 2012-June 2013). Logistic regression models (step-wise procedure) were constructed using as dependent variables "intra-SCCU mortality" or "overall mortality," and variables showing differences (p≤0.1) in bivariate analyses as independent variables. RESULTS: One hundred twenty-one cases were included. Mortality intra-SCCU (R(2)=0.189, p=0.001) was associated with SAPS II (categorized as high if ≥47) (OR=9.55; 95% CI, 1.09-83.85; p=0.042) and 24 h-lactate (≥5.87 categorized as high) (OR=6.90; 95% CI, 1.28-37.08). Overall mortality (R(2)=0.275, p=0.001) was associated with peak PCT (≥100 categorized as high) (OR=11.28; 95% CI, 1.80-70.20), peak lactate (≥1.8 categorized as high) (OR=8.86; 95% CI, 1.51-52.10) and SOFA at admission (≥7 categorized as high) (OR=8.14; 95% CI, 1.69-39.20), but was predicted better (R(2)=0.275, p=0.001) by a single dummy variable (high peak PCT-high peak lactate concentrations) (OR=99.11; 95% CI, 5.21-1885.97; p=0.002). CONCLUSIONS: In the present study, SAPS II and 24 h-lactate concentrations predicted intra-SCCU mortality whereas overall mortality was predicted better by concurrent high PCT and lactate peak concentrations than by clinical scores or by each biomarker separately.

A practice-based observational study on the use of micafungin in Surgical Critical Care Units.

INTRODUCTION: Echinocandins are first-line therapy in critically ill patients with invasive Candida infection (ICI). This study describes our experience with micafungin at Surgical Critical Care Units (SCCUs). METHODS: A multicenter, observational, retrospective study was performed (12 SCCUs) by reviewing all adult patients receiving 100 mg/24h micafungin for ≥72h during ad-mission (April 2011-July 2013). Patients were divided by ICI category (possible, probable + proven), 24h-SOFA (<7, ≥7) and outcome. RESULTS: 72 patients were included (29 possible, 13 probable, 30 proven ICI). Forty patients (55.6%) presented SOFA ≥7. Up to 78.0% patients were admitted after urgent surgery (64.3% with SOFA <7 vs. 90.3% with SOFA ≥7, p=0.016), and 84.7% presented septic shock. In 66.7% the site of infection was intraabdominal. Forty-nine isolates were recovered (51.0% C. albicans). Treatment was empirical (59.7%), microbiologically directed (19.4%), rescue therapy (15.3%), or anticipated therapy and prophylaxis (2.8% each). Empirical treatment was more frequent (p<0.001) in possible versus probable + proven ICI (86.2% vs. 41.9%). Treatment (median) was longer (p=0.002) in probable + proven versus possible ICI (13.0 vs. 8.0 days). Favorable response was 86.1%, without differences by group. Age, blood Candida isolation, rescue therapy, final MELD value and %MELD variation were significantly higher in patients with non-favorable response. In the multivariate analysis (R2=0.246, p<0.001) non-favorable response was associated with positive %MELD variations (OR=15.445, 95%CI= 2.529-94.308, p=0.003) and blood Candida isolation (OR=11.409, 95%CI=1.843-70.634, p=0.009). CONCLUSION: High favorable response was obtained, with blood Candida isolation associated with non-favorable response, in this series with high percentage of patients with intraabdominal ICI, septic shock and microbiological criteria for ICI.

A practice-based observational study identifying factors associated with the use of high-dose tigecycline in the treatment of secondary peritonitis in severely ill patients.

INTRODUCTION: Based on tigecycline linear pharmacokinetic/pharmacodynamics, dose increases have been advocated to maximise activity especially when severe infections with high bacterial load and/or multidrug resistance are suspected. This practice-based observational study explored factors associated with tigecycline administration (100 mg/12h, 200 mg loading dose) in severely ill patients with complicated intra-abdominal infection (cIAI) admitted to four Surgical Critical Care Units (SCCUs). METHODS: Medical records of all consecutive adult patients with cIAI and controlled infection source requiring surgery and admission for ≥ 48 h to SCCU were reviewed and divided into patients treated with a regimen including tigecycline (tigecycline group) and those that not (control group). A logistic regression model was performed using "tigecycline administration" (dependent variable) and variables showing differences (p ≤ 0.1) in bivariate analyses (independent variables). RESULTS: One hundred and twenty one patients were included. In the tigecycline group, higher percentage of patients (vs. controls) presented colon as surgical site (66.7% vs. 41.8%, p = 0.006), nosocomial infection (55.6% vs. 26.9%, p = 0.001), mechanical ventilation (48.1% vs. 28.4%, p = 0.025), chronic renal replacement therapy (40.7% vs. 19.4%, p =0.008), septic shock (72.2% vs. 46.3%, p = 0.004), and higher values of SAPS II (48.0 ± 15.0 vs. 39.6 ± 15.5, p = 0.003), SOFA at admission (7.0 ± 3.3 vs. 5.5 ± 3.7, p = 0.020), lactate-24h (2.5 ± 2.8 vs. 1.6 ± 0.9, p = 0.029) and CRP-72 h (207.4 ± 87.9 vs. 163.7 ± 76.8, p = 0.021). In the multivariate analysis (R2 = 0.187, p < 0.001) nosocomial infection (OR = 7.721; 95%CI = 2.193, 27.179; p = 0.001), colon as infection site (OR = 4.338; 95%CI = 1.432, 13.145; p = 0.009) and CRP-72 h (OR = 1.009 per-unit; 95%CI = 1.002, 1.016; p = 0.012) were associated with tigecycline administration. CONCLUSIONS: In severely ill patients with cIAI, high-dose tigecycline administration was associated with nosocomial origin of cIAI and colon as source infection site.

Procalcitonin-guided therapy may reduce length of antibiotic treatment in intensive care unit patients with secondary peritonitis: A multicenter retrospective study.

PURPOSE: Because procalcitonin (PCT) might be surrogate for antimicrobial discontinuation in general intensive care units (ICUs), this study explored its use for secondary peritonitis in 4 surgical ICUs (SICUs). METHODS: A retrospective study including all consecutive patients with secondary peritonitis, controlled infection source, requiring surgery, and at least 48-hour SICU admission was performed (June 2012-June 2013). Patients were divided following notations in medical records into PCT-guided (notation of PCT-based antibiotic discontinuation) and non-PCT-guided (no notation) groups. RESULTS: A total of 121 patients (52 PCT-guided, 69 non-PCT-guided) were included. No differences in clinical scores, biomarkers, or septic shock (30 [57.7%] PCT-guided vs 40 [58.0%] non-PCT-guided) were found. Length of intra-SICU (median, 5.0 days; both groups) or in-hospital (median, 20.0 vs 17.5 days) stay, and mortality intra-SICU (9.6% vs 13.0%), 28-day (15.4% vs 20.3%), or in-hospital (19.2% vs 29.0%) were not significantly different (PCT-guided vs non-PCT-guided). In septic shock patients, no mortality differences were found (PCT-guided vs non-PCT-guided): 16.7% vs 22.5% (intra-SICU), 26.7% vs 32.5% (28-day), and 33.3% vs 42.5% (in-hospital). Treatment was shorter in the PCT-guided group (5.1 ±2.1 vs 10.2 ± 3.7 days, P < .001), without differences between patients with and without septic shock. CONCLUSION: Procalcitonin guidance produced 50% reduction in antibiotic duration (P < .001, log-rank test).