Clinical Effect of Alpha-1 Antitrypsin Deficiency in Antineutrophil Cytoplasmic Antibody-associated Vasculitis: Results from a French Retrospective Monocentric Cohort.

OBJECTIVE: Deficiency in alpha-1 antitrypsin (AAT) is a possible pathogenic cofactor in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the clinical effect of AAT deficiency remains poorly established in this setting. This study aimed to describe the clinical phenotypes and outcomes of AAV according to AAT phenotypes. METHODS: This study was conducted retrospectively at Caen University Hospital and included all consecutive granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with positive proteinase 3-ANCA or myeloperoxidase-ANCA, from January 2000 or September 2011, respectively, to June 2016. AAT dosage (nephelometry) and phenotyping (isoelectric focusing in agarose gel) were performed. RESULTS: Among the 142 patients with AAV, including 88 GPA and 54 MPA, 102 (72%) had the MM phenotype, 5 (4%) had a nonpolymerogenic M-variant phenotype, 18 (13%) had the deficient allele MZ, 12 (8%) had MS, 2 (1%) had ZZ, 2 (1%) had SZ, and 1 (1%) had SS. M, Z, and S allele frequencies were 84%, 8%, and 6%, respectively. No association was observed between AAT deficiency and ANCA subtype or AAV phenotype, except for intraalveolar hemorrhage (IAH), which was more frequent in patients harboring at least 1 of the deficient Z or S alleles than in those without any deficient alleles (p < 0.01). Global, renal, or relapse-free survival rates were similar for all subgroups. CONCLUSION: This study shows that AAT deficiency confers, independently of ANCA subtype, a higher risk of IAH. Prospective studies are required to refine these data and to assess the need for replacement therapy in AAT-deficient patients with AAV.

Three-month antibiotic therapy for early-onset postoperative spinal implant infections.

BACKGROUND: Optimal duration and modalities of antibiotic therapy for early-onset spinal implant infection (EOSII) remain controversial. METHODS: Between November 2004 and November 2007, we conducted a prospective, monocentric study to assess the efficacy of a 3-month course of antibiotics for patients diagnosed with EOSII, as defined by a proven deep infection of the surgical site occurring within 30 days after spinal instrumented surgery. All patients with EOSII underwent surgical debridement with implant retention. Combination antibiotic therapy was administered intravenously for 2 weeks. Treatment was switched orally for the following 10 weeks. RESULTS: 50 patients matched the inclusion criteria and were included in this study. The median age was 68 (interquartile range [IQR]: 51-75) years; the median ASA score was 2 (IQR: 2-2). Emergency spinal surgery had been performed in 18 patients. Staphylococcus aureus was the most frequently isolated pathogen (n=27), followed by Enterobacteriaceae (n=22) and coagulase-negative staphylococci (n=6). Seventeen patients had polymicrobial infections, and 13 patients (26%) had bacteremia. The median time from the first symptoms of infection to debridement surgery was 3 days (IQR: 2-5 days). Three patients underwent 2 debridement surgeries. The median follow-up was 43 (IQR: 34-54) months. The 2-year survival rate for those who did not experience treatment failure was 88% (95% confidence interval [CI]: 75.7%-95.5%). Three patients experienced treatment failure (6%, 95% CI: 1.3%-16.5%), including 1 relapse due to methicillin-susceptible S. aureus and 2 reinfections with another pathogen. CONCLUSIONS: In this homogenous cohort of 50 patients with EOSII, treatment consisting of debridement surgery with implant retention followed by combination antibiotic therapy for 3 months appeared safe and effective.

Malaria in pregnant woman masquerading as HELLP syndrome.

Malaria may be complicated by development of thrombocytopenia, elevated liver enzymes, and/or hemolysis, which may be difficult to distinguish from HELLP (hemolytic anemia; elevated liver enzymes; low platelet count) syndrome in a pregnant patient. A 33-year-old woman developed a HELLP-like syndrome and persistent fever postpartum without symptoms of preeclampsia. A malaria blood smear was performed and was positive for Plasmodium falciparum. The patient was immediately treated with quinine. The follow-up was uneventful with total disappearance of fever and prompt resolution of biochemical signs of HELLP-like syndrome 3 days later. Malaria in a pregnant woman can masquerade as HELLP syndrome. The wide overlap in symptoms (headache, malaise, digestive symptoms) does not suggest that symptoms would be effective in differentiating malaria and preeclampsia. A recent travel in endemic area, associated with malaria blood smear and clinic examination, should be the key of the differential diagnosis.

Risk factors for Enterobacteriaceae bacteremia after liver transplantation.

Enterobacteriaceae are now the predominant pathogens isolated in bloodstream infections complicating orthotopic liver transplantation (OLT). We conducted a retrospective cohort study of patients who underwent OLT in a University hospital between 01/01/1997 and 31/03/2003 to investigate the risk factors of Enterobacteriaceae bacteremia (EB) after OLT. EB was defined as the isolation of an Enterobacteriaceae species from at least one blood culture within 3 months following OLT. Pre-, per- and postoperative variables were collected from the medical records and analyzed in relation to EB. Forty (12.5%) of the 320 patients developed EB. The origin of EB was abdominal in 32% of the patients, urinary in 18%, pulmonary in 10%, and primary in the remaining 40% of the patients. Two-thirds of EB occurred within 1 month following OLT. The main pathogens were Escherichia coli (42%), Enterobacter cloacae (17%) and Klebsiella pneumoniae (17%). Susceptibility rates varied from 82.5% for ciprofloxacin to 95% for amikacin. Fourteen patients (35%) with EB died. Variables significantly associated with EB after multivariate analysis were a MELD score >20 (OR: 2.79 [1.24-6.30], P=0.013), transplantation for posthepatitic B (OR: 4.47 [1.67-11.98], P=0.03) or posthepatitic C (OR: 3.79 [1.59-9.01], P=0.03) cirrhosis, a positive bile culture (OR: 3.47 [1.19-10.13], P=0.023) and return to surgery (including retransplantation) (OR: 2.72 [1.32-5.58], P=0.006). EB is a frequent and severe complication following OLT. Patients grafted for a posthepatitic cirrhosis, with a severe pretransplantation status, with a positive bile culture and those undergoing reoperation have a high risk of developing EB.

Risk factors for Staphylococcus aureus infection in liver transplant recipients.

Staphylococcus aureus is the leading cause of bacterial infection in liver transplant recipients. Preoperative nasal carriage of methicillin-resistant S. aureus (MRSA) is associated with a high risk of infection. We conducted a retrospective cohort study in order to identify independent risk factors for early-onset S. aureus infection after liver transplantation. Patients were screened preoperatively for methicillin-susceptible S. aureus (MSSA) and MRSA nasal carriage. Risk factor analysis was performed by univariate analysis followed by stepwise logistic regression. Of the 323 patients included, 63 (19.5%) patients developed S. aureus infection (36 MRSA, 27 MSSA) within 1 month of surgery. Variables significantly associated with infection in the univariate analysis were MRSA and MSSA nasal carriage, alcoholic cirrhosis, absence of hepatocellular carcinoma, decreased prothrombin ratio, and presence of ascites. In the multivariate analysis, MRSA carriage (odds ratio [OR]: 20.9, P < 0.0001), MSSA carriage (OR: 3.4, P = 0.0004), alcoholic cirrhosis (OR: 2.4, P = 0.01) and decreased prothrombin ratio (OR: 1.2, P = 0.01) were independent predictors of infection. Molecular typing showed that the infecting isolate was identical to the isolate from the nose in most patients. In conclusion, preoperative nasal carriage of MRSA and MSSA is an independent risk factor for S. aureus infection in liver transplant recipients. The infection is most often of endogenous origin. Alcoholic cirrhosis and the severity of liver failure are also associated with a high risk of infection.