Semi-Conservative Treatment Versus Radical Surgery in Abdominal Aortic Graft and Endograft Infections.

OBJECTIVE: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort. METHODS: Patients with abdominal AGI related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for the definition of AGI. Multivariable regression was performed to identify factors associated with mortality. RESULTS: One hundred and sixty-nine patients with surgically treated abdominal AGI were identified, comprising 43 SC (14 endografts; 53% with a graft enteric fistula [GEF] in total) and 126 RS (26 endografts; 50% with a GEF in total). The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan-Meier estimated five year survival for SC vs. RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan-Meier estimated five year survival for SC patients with a GEF vs. without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC with RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in five year survival comparing SC vs. RS (HR 1.0, 95% CI 0.6 - 1.5). CONCLUSION: In this national AGI cohort, there was no mortality difference comparing SC and RS for AGI when adjusting for comorbidities. Presence of GEF probably negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC treated patients.

Invasive fungal infection by Peziza ostracoderma in an immunocompromised patient.

We report for the first time a case of disseminated infection caused by Peziza ostracoderma, a mold not previously associated with invasive infections in humans. P. ostracoderma occurs in natural and sterilized soil and may cause hypersensitivity pneumonitis in greenhouse workers. The immunocompromised patient presented with neutropenic fever that did not respond to broad-spectrum antibiotics and developed multiple skin and lung lesions. A skin biopsy demonstrated an angioinvasive mold, identified as Peziza ostracoderma by culture and DNA sequencing. Minimum inhibitory concentration (MIC) for amphotericin B was 0.125 mg/L, for isavuconazole 0.125 mg/L, for voriconazole 0.06 mg/L, and for posaconazole 0.03 mg/L. The skin lesions have resolved completely, and the lung lesions have decreased significantly in size after 14 months of mold-active antifungal therapy, mostly isavuconazole. In conclusion, Peziza species can be opportunistic pathogens causing considerable morbidity in immunocompromised hosts. The infection may be successfully treated with mold-active antifungal drugs.

The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting.

OBJECTIVE: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs). METHODS: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures. RESULTS: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P = .051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year. CONCLUSION: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings.

Population pharmacokinetics of cefotaxime in intensive care patients.

PURPOSE: To characterise the pharmacokinetics and associated variability of cefotaxime in adult intensive care unit (ICU) patients and to assess the impact of patient covariates. METHODS: This work was based on data from cefotaxime-treated patients included in the ACCIS (Antibiotic Concentrations in Critical Ill ICU Patients in Sweden) study. Clinical data from 51 patients at seven different ICUs in Sweden, given cefotaxime (1000-3000 mg given 2-6 times daily), were collected from the first day of treatment for up to three consecutive days. In total, 263 cefotaxime samples were included in the population pharmacokinetic analysis. RESULTS: A two-compartment model with linear elimination, proportional residual error and inter-individual variability (IIV) on clearance and central volume of distribution best described the data. The typical individual was 64 years, with body weight at ICU admission of 92 kg and estimated creatinine clearance of 94 mL/min. The resulting typical value of clearance was 11.1 L/h, central volume of distribution 5.1 L, peripheral volume of distribution 18.2 L and inter-compartmental clearance 14.5 L/h. The estimated creatinine clearance proved to be a significant covariate on clearance (p < 0.001), reducing IIV from 68 to 49%. CONCLUSION: A population pharmacokinetic model was developed to describe cefotaxime pharmacokinetics and associated variability in adult ICU patients. The estimated creatinine clearance partly explained the IIV in cefotaxime clearance. However, the remaining unexplained IIV is high and suggests a need for dose individualisation using therapeutic drug monitoring where the developed model, after evaluation of predictive performance, may provide support.

Editor's Choice - Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study.

OBJECTIVE: Abdominal aortic graft and endograft infection (AGI) is primarily treated by resection of the infected graft and restoration of distal perfusion through extra-anatomic bypass (EAB) or in situ reconstruction/repair (ISR). The aim of this study was to compare these surgical strategies in a nationwide multicentre retrospective cohort study. METHODS: The Swedish Vascular Registry (Swedvasc) was used to identify surgically treated abdominal AGIs in Sweden between January 1995 and May 2017. The primary aim was to compare short and long term survival, as well as complications for EAB and ISR. RESULTS: Some 126 radically surgically treated AGI patients were identified - 102 graft infections and 24 endograft infections - treated by EAB: 71 and ISR: 55 (23 neo-aorto-iliac systems, NAISs). No differences in early 30 day (EAB 81.7% vs. ISR 76.4%, p = .46), or long term five year survival (48.2% vs. 49.9%, p = .87) were identified. There was no survival difference comparing NAIS to other ISR strategies. The frequency of recurrent graft infection during follow up was similar: EAB 20.3% vs. ISR 17.0% (p = .56). Survival and re-infection rates of the new conduit did not differ between NAIS and other ISR strategies. Age ≥ 75 years (odds ratio [OR] 4.0, confidence interval [CI] 1.1 - 14.8), coronary artery disease (OR 4.2, CI 1.2 - 15.1) and post-operative circulatory complications (OR 5.2, CI 1.2 - 22.5) were associated with early death. Prolonged antimicrobial therapy (> 3 months) was associated with reduced long term mortality (HR 0.3, CI 0.1 - 0.9). CONCLUSION: In this nationwide multicentre study comparing outcomes of radically treated AGI, no differences in survival or re-infection rate could be identified comparing EAB and ISR.

Nationwide Study of the Treatment of Mycotic Abdominal Aortic Aneurysms Comparing Open and Endovascular Repair.

BACKGROUND: No reliable comparative data exist between open repair (OR) and endovascular aneurysm repair (EVAR) for mycotic abdominal aortic aneurysms (MAAAs). This nationwide study assessed outcomes after OR and EVAR for MAAA in a population-based cohort. METHODS: All patients treated for MAAAs in Sweden between 1994 and 2014 were identified in the Swedish vascular registry. The primary aim was to assess survival after MAAA with OR and EVAR. Secondary aims were analyses of the rate of recurrent infections and reoperations, and time trends in surgical treatment. Survival was analyzed using Kaplan-Meier and log-rank tests. A propensity score-weighted correction for risk factor differences in the 2 groups was performed, including the operation year to account for differences in treatment and outcomes over time. RESULTS: We identified 132 patients (0.6% of all operated abdominal aortic aneurysms in Sweden). Mean age was 70 years (standard deviation, 9.2), and 50 presented with rupture. Survival at 3 months was 86% (95% confidence interval, 80%-92%), at 1 year 79% (72%-86%), and at 5 years 59% (50%-68%). The preferred operative technique shifted from OR to EVAR after 2001 (proportion EVAR 1994-2000 0%, 2001-2007 58%, 2008-2014 60%). Open repair was performed in 62 patients (47%): aortic resection and extra-anatomic bypass (n=7), in situ reconstruction (n=50), and patch plasty (n=3); 2 patients died intraoperatively. EVAR was performed in 70 patients (53%): standard EVAR (n=55), fenestrated/branched EVAR (n=8), and visceral deviation with stent grafting (n=7); no deaths occurred intraoperatively. Survival at 3 months was lower for OR than for EVAR (74% versus 96%, P<0.001), with a similar trend present at 1 year (73% versus 84%, P=0.054). A propensity score-weighted risk-adjusted analysis confirmed the early better survival associated with EVAR. During median follow-up of 36 and 41 months for OR and EVAR, respectively, there was no difference in long-term survival (5 years 60% versus 58%, P=0.771), infection-related complications (18% versus 24%, P=0.439), or reoperation (21% versus 24%, P=0.650). CONCLUSION: This study demonstrates a paradigm shift in treatment of MAAA in Sweden, with EVAR being the preferred treatment modality. EVAR was associated with improved short-term survival in comparison with OR, without higher associated incidence of serious infection-related complications or reoperations.

Significant differences when using creatinine, modification of diet in renal disease, or cystatin C for estimating glomerular filtration rate in ICU patients.

BACKGROUND: Renal dysfunction is associated with increased morbidity and mortality in intensive care patients. In most cases the glomerular filtration rate (GFR) is estimated based on serum creatinine and the Modification of Diet in Renal Disease (MDRD) formula, but cystatin C-estimated GFR is being used increasingly. The aim of this study was to compare creatinine and MDRD and cystatin C-estimated GFR in intensive care patients. METHODS: Retrospective observational study was performed, on patients treated within the general intensive care unit (ICU) during 2004-2006, in a Swedish university hospital. RESULTS: GFR markers are frequently ordered in the ICU; 92% of the patient test results had cystatin C-estimated GFR (eGFR(cystatinC)) ≤ 80 mL/min/1.73 m(2), 75% had eGFR ≤ 50 mL/min/1.73 m(2), and 30% had eGFR ≤ 20 mL/min/1.73 m(2). In contrast, only 46% of the patients had reduced renal function assessed by plasma creatinine alone, and only 47% had eGFR(MDRD) ≤ 80 mL/min/1.73 m(2). The mean difference between eGFR(MDRD) and eGFR(cystatinC) was 39 mL/min/1.73 m(2) for eGFR(cystatinC) values ≤ 60 mL/min/1.73 m(2). CONCLUSIONS: GFR is commonly assessed in the ICU. Cystatin C-estimated GFR yields markedly lower GFR results than plasma creatinine and eGFR(MDRD). Many pharmaceuticals are eliminated by the kidney, and their dosage is adjusted for kidney function. Thus, the differences in GFR estimates by the methods used indicate that the GFR method used in the intensive care unit may influence the treatment.

Subcellular localization and mobilization of carcinoembryonic antigen-related cell adhesion molecule 8 in human neutrophils.

The subcellular localization and mobilization of carcinoembryonic antigen-related cell adhesion molecule 8 (CEACAM8) was investigated quantitatively in human neutrophils. In resting neutrophils the majority of CEACAM8 was present in the secondary granules, and a small amount of CEACAM8 was present in a light membrane fraction. Stimulation of the neutrophils with phorbol 12-myristate 13-acetate caused a dramatic increase in the content of CEACAM8 in the light membrane fraction, suggesting a translocation of CEACAM8 to the plasma membrane from intracellular pools. The cellular content of CEACAM8 in the neutrophils was estimated to be 82.4 +/- 8.9 ng/10(6) cells (mean +/- SE, n = 10). Administration of granulocyte colony-stimulating factor (G-CSF) to healthy individuals resulted in an increased content of CEACAM8 in neutrophils on day 1, which decreased on day 4. However, the content of CEACAM8 in the light membrane fraction was increased on day 4, possibly due to the stimulation by induced secondary cytokines, such as tumour necrosis factor-alpha (TNF-alpha). This study establishes the secondary granules as the major intracellular pools of CEACAM8 in human neutrophils, from which it may translocate to the plasma membranes upon stimulation of the cells. The translocation of CEACAM8 seen in vivo after G-CSF administration is probably indirect and caused by cytokines such as TNF-alpha.