Signs Of Persistent Infection Research Articles

Unusual infections and diabetes: dangerous fungi

Unusual infections and diabetes: dangerous fungi

Compassionate use of meropenem/vaborbactam for infections caused by KPC-producing Klebsiella pneumoniae: a multicentre study.

ObjectivesTo explore the real-life performance of meropenem/vaborbactam for treating serious KPC-producing Klebsiella pneumoniae infections, including those resistant to ceftazidime/avibactam.MethodsA retrospective observational cohort study was conducted in 12 Italian hospitals. Enrolled patients had K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) infections (59.5% of which were ceftazidime/avibactam resistant). Patients who received ≥72 h of meropenem/vaborbactam therapy (with or without other antimicrobials) in a compassionate-use setting were included.ResultsThe 37 infections (all hospital-acquired) were mainly bacteraemic (BSIs, n = 23) or lower respiratory tract infections (LRTIs, n = 10). Clinical cure was achieved in 28 (75.6%) cases and microbiologically confirmed in all 25 with follow-up cultures. Three (10.7%) of the 28 clinical cures (all BSIs, 2/3 microbiologically confirmed) were followed by in-hospital recurrences after meropenem/vaborbactam was discontinued (median interval: 18 days). All three recurrences were susceptible to meropenem/vaborbactam and successfully managed with meropenem/vaborbactam combined with colistin or fosfomycin. Nine patients (24.3%) (all with BSIs or LRTIs) died in hospital with persistent signs of infection. Most were aged over 60 years, with high comorbidity burdens and INCREMENT scores ≥8. Only one had received meropenem/vaborbactam monotherapy. Six began meropenem/vaborbactam therapy >48 h after infection onset. Outcomes were unrelated to the isolate’s ceftazidime/avibactam susceptibility status. The single adverse event observed consisted of severe leukopenia with thrombocytopenia.ConclusionsWith the well-known limitations of real-life retrospective studies, our results support previous findings indicating that meropenem/vaborbactam therapy will be a safe, effective tool for managing serious KPC-Kp infections, including the increasing proportion displaying resistance to ceftazidime/avibactam.

Neospora caninum DNA distribution in tissues of gerbils as experimental models of chronic neosporosis

ABSTRACT Neospora caninum is the main etiologic agent of neosporosis in domestic animals and its pathogenesis comprises two characteristic phases: acute and chronic. Rodents are used as experimental models to mimic acute and chronic bovine neosporosis. In this study, we inoculated a total of 27 female gerbils, with different doses of N. caninum tachyzoites aiming to induce chronic disease. DNA was extracted from different organs of each animal after spontaneous death or euthanasia. Encephalic tissues were submitted to a highly sensitive real time PCR aiming to detect chronically infected animals. All the other samples were submitted to standard PCR. A total of 11 gerbils died due to acute neosporosis, as confirmed by N. caninum DNA detection in organs. 5x103 tachyzoites/mL of N. caninum was the dosage of antigen that can induce chronic infection in gerbils. In the encephalon sections of some animals that showed clinical signs of persistent infection, we found 70% positive for the anterior encephalon section, suggesting this area as preferential for cyst formation. Therefore, we determined the doses of tachyzoites that cause acute or chronic infection and detection of positive tissues, preferably, systemic organs during acute and encephalon in chronic phases.

Short-course antibiotic regimen compared to conventional antibiotic treatment for gram-positive cocci infective endocarditis: randomized clinical trial (SATIE)

BackgroundMost serious complications of infective endocarditis (IE) appear in the so-called “critical phase” of the disease, which represents the first days after diagnosis. The majority of patients overcoming the acute phase has a favorable outcome, yet they remain hospitalized for a long period of time mainly to complete antibiotic therapy. The major hypothesis of this trial is that in patients with clinically stable IE and adequate response to antibiotic treatment, without signs of persistent infection, periannular complications or metastatic foci, a shorter antibiotic time period would be as efficient and safe as the classic 4 to 6 weeks antibiotic regimen.MethodsMulticenter, prospective, randomized, controlled open-label, phase IV clinical trial with a non-inferiority design to evaluate the efficacy of a short course (2 weeks) of parenteral antibiotic therapy compared with conventional antibiotic therapy (4–6 weeks).Sample: patients with IE caused by gram-positive cocci, having received at least 10 days of conventional antibiotic treatment, and at least 7 days after surgery when indicated, without clinical, analytical, microbiological or echocardiographic signs of persistent infection. Estimated sample size: 298 patients. Intervention: Control group: standard duration antibiotic therapy, (4 to 6 weeks) according to ESC guidelines recommendations. Experimental group: short-course antibiotic therapy for 2 weeks. The incidence of the primary composite endpoint of all-cause mortality, unplanned cardiac surgery, symptomatic embolisms and relapses within 6 months after the inclusion in the study will be prospectively registered and compared.ConclusionsSATIE will investigate whether a two weeks short-course of intravenous antibiotics in patients with IE caused by gram-positive cocci, without signs of persistent infection, is not inferior in safety and efficacy to conventional antibiotic treatment (4–6 weeks).Trial registrationClinicalTrials.gov Identifier: NCT04222257 (January 7, 2020).EudraCT 2019–003358-10.

C-Reactive Protein Level at Time of Discharge Is Not Predictive of Risk of Reoperation or Readmission in Children With Septic Arthritis.

Purpose: C-reactive protein (CRP) level is used at our tertiary pediatric hospital in the diagnosis, management, and discharge evaluation of patients with septic arthritis. The purpose of this study was to evaluate the efficacy of a discharge criterion of CRP < 2.0 mg/dL for patients with septic arthritis in preventing reoperation and readmission. We also aimed to identify other risk factors of treatment failure.Methods: Patients diagnosed with septic arthritis between January 1, 2007 and December 31, 2017 were identified with ICD 9/10 and related CPT codes. Systematic chart reviews were performed to obtain demographic data, infection characteristics, and treatment details. Bivariate tests of associations between potential risk factors and readmission and reoperation were performed. Quantitative variables were analyzed using Mann-Whitney tests and categorical variables were analyzed using Chi-square tests.Results: One hundred and eighty-three children with septic arthritis were included in the study. Seven (3.8%) were readmitted after hospital discharge for further management, including six who required reoperation. Mean CRP at discharge for single-admission patients was 1.71 mg/dL (± 1.07) and 1.96 mg/dL (± 1.19) for the readmission group (p = 0.664). Forty-eight children (25.9%) had CRP values greater than the recommended 2.0 mg/dL at discharge. Only three of these patients (6.2%) were later readmitted. The only common variable of the readmitted children was an antibiotic-resistant or atypical causative bacteria.Conclusions: CRP levels are useful in monitoring treatment efficacy of septic arthritis in children but are not reliable as a discharge criterion to prevent readmission or reoperation. We recommend determining discharge readiness on the basis of clinical improvement and down-trending CRP values. There was a higher risk of readmission in children with an antibiotic-resistant or atypical causative bacteria. Close monitoring of these patients and those with negative cultures at time of discharge is suggested to identify signs of persistent infection.Level of evidence: III, retrospective cohort study.

Characteristics and clinical outcomes after treatment of a national cohort of PCR-positive Lyme arthritis

ObjectivesTo describe the clinical and microbiological characteristics and outcomes after antibiotic treatment of a national cohort of patients with Lyme arthritis confirmed by PCR testing on synovial fluid and by serology, when available. MethodsUsing the French National Reference Center for Borrelia database, patients with a positive PCR on synovial fluid for Borrelia were identified. Patient clinical and biological characteristics were reviewed from patient records. Long-term outcomes after treatment were studied through a questionnaire and with follow-up data. ResultsAmong 357 synovial fluid testing by PCR between 2010 and 2016, 37 (10.4%) were positive for Borrelia. Patients’ median age was 36 years (range 6–78) with 61% of men and 28% patients under 18. The presentation was monoarticular in 92% and the knee was involved in 97%. Contrary to the Borrelia species repartition in European ticks, B. burgdorferi sensu stricto was the most prevalent species found in synovial fluid (54%) followed by B. azfelii (29%) and B. garinii (17%). Antibiotic treatments were mainly composed of doxycycline (n = 24), ceftriaxone (n = 10) and amoxicillin (n = 6), for a median duration of 4 weeks (range 3–12). Despite a properly conducted treatment, 34% of patients (n = 12) developed persistent synovitis for at least 2 months (median duration 3 months, range 2–16). Among those, 3 developed systemic inflammatory oligo- or polyarthritis in previously unaffected joints with no signs of persistent infection (repeated PCR testing negative), which mandated Disease-Modifying Antirheumatic Drugs (DMARD) introduction, leading to remission. ConclusionIn France and contrary to ticks ecology, Lyme arthritis is mainly caused by B. burgdorferi sensu stricto. Despite proper antibiotic therapy, roughly one third of patients may present persistent inflammatory synovitis and a small proportion may develop systemic arthritis. In such cases, complete remission can be reached using DMARD.

Presurgical localization of infected avascular bone segments in chronic complicated posttraumatic osteomyelitis in the lower extremity using dual-tracer PET/CT

BackgroundLocalizing and removing the infected sequestrum in long-standing trauma-related chronic osteomyelitis remains a clinical challenge. PET/CT with 18F-fluorodeoxyglucose (FDG-PET) has a high sensitivity for chronic osteomyelitis and 18F-sodium-fluoride PET/CT (NaF-PET) has a high specificity for identifying non-viable bone. Combining both, high signal on FDG-PET in the bone without signal on NaF-PET could potentially guide surgery to become more precise with curative intent.Eight patients with long-standing (average 22 years) posttraumatic (n = 7) or postoperative (n = 1) chronic osteomyelitis in the lower extremity and with multiple futile attempts for curative surgery were recruited in this prospective pilot study. FDG-PET and NaF-PET were performed within a week in between using standard scanning protocols. The most likely location of the culprit sequestrum was identified and was surgically removed. Based on perioperative tissue cultures, antibiotics were given for 6–8 months. Dual-tracer (FDG- and NaF-PET/CT) was performed again after 12 months to rule out persisting signs of infection.ResultsA likely culprit sequestrum could preoperatively be identified by dual-tracer PET in all eight cases and in four cases an additional sequestrum was identified at a location with no clinical sign of infection. The infected necrotic tissue was removed during surgery. Follow-up dual-tracer PET revealed no signs of persistent infection. All patients recovered with no clinical signs of recurrence for a follow-up of mean 4.5 (SD 1.3) years.ConclusionsDual-tracer PET/CT with FDG and NaF allows successful precise surgery with curative intent in patients with long-standing complicated posttraumatic chronic osteomyelitis with severely deranged anatomy.

Orbital implant exposure after Acanthamoeba panophthalmitis

PurposeAcanthamoeba is a protozoa that can lead to severe ocular disease and sequelae. Although intraocular Acanthamoeba infection is rare, the following case demonstrates an unusual presentation of recurrent Acanthamoeba infection in a 30 year old contact lens wearing male. ObservationsAfter presenting with recurrent Acanthamoeba keratitis and undergoing various treatments, the patient developed nodular scleritis, which evolved into panophthalmitis, and ultimately, required enucleation. Eight months post-operatively, the patient developed orbital implant exposure secondary to persistent Acanthamoeba infection and underwent removal of the implant and aggressive, systemic treatment involving a multispecialty care team. He then underwent placement of a dermis fat graft and had no signs of persistent infection at the time of last follow-up, which was 24 months after placement of the dermis fat graft. Conclusionsand Importance: To the authors' knowledge, this is the first known case of Acanthamoeba infection causing orbital implant exposure. Persistent infection should be considered in Acanthamoeba patients who have undergone enucleation and have orbital implant exposure. Better knowledge regarding the pathogenesis and extracorneal complications of this challenging disease may improve patient care and outcomes.

Serum D-Dimer Test Is Promising for the Diagnosis of Periprosthetic Joint Infection and Timing of Reimplantation.

Despite the availability of a battery of tests, the diagnosis of periprosthetic joint infection (PJI) continues to be challenging. Serum D-dimer assessment is a widely available test that detects fibrinolytic activities that occur during infection. We hypothesized that patients with PJI may have a high level of circulating D-dimer and that the presence of a high level of serum D-dimer may be a sign of persistent infection in patients awaiting reimplantation. This prospective study was initiated to enroll patients undergoing primary and revision arthroplasty. Our cohort consisted of 245 patients undergoing primary arthroplasty (n = 23), revision for aseptic failure (n = 86), revision for PJI (n = 57), or reimplantation (n = 29) or who had infection in a site other than a joint (n = 50). PJI was defined using the Musculoskeletal Infection Society criteria. In all patients, serum D-dimer level, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level were measured preoperatively. The median D-dimer level was significantly higher (p < 0.0001) for the patients with PJI (1,110 ng/mL [range, 243 to 8,487 ng/mL]) than for the patients with aseptic failure (299 ng/mL [range, 106 to 2,571 ng/mL). Using the Youden index, 850 ng/mL was determined as the optimal threshold value for serum D-dimer for the diagnosis of PJI. Serum D-dimer outperformed both ESR and serum CRP, with a sensitivity of 89% and a specificity of 93%. ESR and CRP had a sensitivity of 73% and 79% and a specificity of 78% and 80%, respectively. The sensitivity and specificity of ESR and CRP combined was 84% (95% confidence interval [CI], 76% to 90%) and 47% (95% CI, 36% to 58%), respectively. It appears that serum D-dimer is a promising marker for the diagnosis of PJI. This test may also have a great utility for determining the optimal timing of reimplantation. Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Risk Factors, Clinical Presentation, and Outcome of Acinetobacter baumannii Bacteremia.

Infections caused by Acinetobacter baumannii (AB), an increasingly prevalent nosocomial pathogen, have been associated with high morbidity and mortality. We conducted this study to analyze the clinical features, outcomes, and factors influencing the survival of patients with AB bacteremia. We retrospectively examined the medical records of all patients developing AB bacteremia during their hospital stay at a tertiary care hospital in Beirut between 2010 and 2015. Ninety episodes of AB bacteremia were documented in eighty-five patients. Univariate analysis showed that prior exposure to high dose steroids, diabetes mellitus, mechanical ventilation, prior use of colistin and tigecycline, presence of septic shock, and critical care unit stay were associated with a poor outcome. High dose steroids and presence of septic shock were significant on multivariate analysis. Crude mortality rate was 63.5%. 70.3% of the deaths were attributed to the bacteremia. On acquisition, 39 patients had septicemia. Despite high index of suspicion and initiation of colistin and/or tigecycline in 18/39 patients, a grim outcome could not be averted and 37 patients died within 2.16 days. Seven patients had transient benign bacteremia; three of which were treated with removal of the line. The remaining four did not receive any antibiotics due to withdrawal of care and died within 26.25 days of acquiring the bacteremia, with no signs of persistent infection on follow up. A prolonged hospital stay is frequently associated with loss of functionality, and steroid and antibiotic exposure. These factors seem to impact the mortality of AB bacteremia, a disease with high mortality rate and limited therapeutic options.

Infected Total Ankle Arthroplasty

Infections in total ankle arthroplasty are a serious complication, about which there is little information in the current literature. This is a retrospective review of infected total ankle arthroplasty at one institution from 1995 to 2012. Risk factors were compared between patients with infected total ankle arthroplasty and age- and sex-matched patients who did not have infection (control patients) within the same time period. 966 patients with total ankle arthroplasty were reviewed, and 29 cases of infected total ankle arthroplasty (3.2%) were identified. The incidence of infection in primary ankle arthroplasty was 2.4% and in revision arthroplasty was 4%. Risk factors for infection in our cohort included diabetes, prior ankle surgery, and wound healing problems more than 14 days postoperatively. No significant difference was found between groups with respect to risk factors including smoking, body mass index, and operative time. At latest follow-up, none of the patients had signs of persistent infection. Operative intervention of infected total ankle arthroplasty resulted in limb salvage in 79% of cases (a 21% amputation rate). At final follow-up, 65.5% of cases were infection-free with retained arthroplasty. This was achieved by irrigation and debridement alone, 1-stage fusion, and most often 2-stage revision. The final outcome was fusion in 3 of 29 cases (10.3%). Given the morbidity of infected ankle arthroplasty, careful consideration should be made about performing arthroplasty in patients with multiple prior surgeries and comorbidities that predispose to wound-healing difficulties. Level III, retrospective comparative study.

Thrombocytopenia, a new marker of bad prognosis in patients with infective endocarditis

Aim: Thrombocytopenia in patients with sepsis has been described as a marker of bad prognosis. Our purpose was to analyze if the presence of thrombocytopenia has a prognostic impact in patients with left-sided infective endocarditis (IE). Methods: We analyzed 698 consecutive episodes of IE prospectively recruited in three referral hospitals between 1996 and 2011. They were classified in two groups: Group I (n=213) episodes of IE who had thrombocytopenia in blood analysis at admission; and Group II (n=485) those who did not have it. Thrombocytopenia was defined as a platelet count below 150000/μl. Results: The age and gender distribution were similar in both groups. Regarding to comorbidities, diabetes (25.4% vs. 18.3%, p=0.03), chronic anemia (24.5% vs. 17.6%, p= 0.03) and immunosuppression (11.8% vs. 4.5%, p<0.001) were more frequent in Group I. We found a greater percentage of prosthetic valves in Group II, while patients without any previous cardiopathy were more prevalent in Group I (29.6% vs. 21.6%, p=0.02). S. aureus (28.6% vs. 10.9%, p<0.001) and Gram negative bacilli (8% vs. 3.1%, p=0.004) were more frequently isolated in Group I, were S. viridans (8% vs. 15.1%, p=0.01) and culture negative IE (10.3 vs. 16.3, p=0.04) were more common in Group II. Clinical presentation with neurological (p<0.001), renal (p=0.05), cutaneous (p<0.001) manifestations and septic shock (12.2% vs. 3.5%, p<0.001) at admission were more frequent in Group I. These patients showed also more frequency of hemorrhagic skin lesions (11% vs. 4%, p=0.002), splenomegaly (14.2% vs 7.4%, p=0.005) and coma (5.6% vs. 0.8%, p<0.001). Presence of pseudoaneurysms were more frequently found in Group II (12.2% vs. 18.9%, p=0.03). There were no differences in other echocardiographic findings (valvular insufficiency, presence and size of vegetations). During hospitalization, persistent signs of infection (44.5% vs. 31.8%, p=0.001) and septic shock were more frequent in Group I (27% vs. 13.5%, p<0.001). The need of surgery was similar in both groups (53.5% vs. 56.1%, p=0.535), but much higher mortality was observed in patients with thrombocytopenia (40.4% vs. 25.3%, p<0.001). Conclusions: Thrombocytopenia at admission of patients with IE identifies a highest risk group. Causative microorganisms are more virulent in this group. These patients develop septic shock more frequently and showed higher mortality.

Successful Clinical Use of Daptomycin-Impregnated Bone Cement in Two-Stage Revision Hip Surgery for Prosthetic Joint Infection

To describe the safe and successful use of daptomycin-impregnated polymethyl methacrylate (PMMA) bone cement in the treatment of a case of recurrent prosthetic joint infection in a patient with multiple antibiotic allergies and past colonization with multiply antibiotic-resistant organisms. A 79-year-old female had a history of chronic recurrent left prosthetic hip infection. The patient had confirmed allergies to multiple antibiotics and a past history of colonization with methicillin-resistant Staphylococcus aureus. At first-stage revision surgery, the infected prosthesis was removed and samples were sent for microbiologic culture. A spacer device was fashioned, with incorporation of daptomycin and gentamicin into the PMMA bone cement at a concentration of 5% w/w for each antibiotic. Systemic daptomycin and gentamicin were administered postoperatively for 14 days. Propionibacterium acnes was isolated from deep-tissue specimens. The patient made excellent postoperative progress and was discharged after 2 weeks. Second-stage revision surgery was performed at 6 months, with no signs of persistent infection. She remained well, pain free, and mobilizing independently 2 years later. Daptomycin, a cyclic lipopeptide antibiotic, is approved for systemic treatment of endocarditis and skin and soft tissue infections. In vitro data demonstrate acceptable drug elution from and tensile strength of daptomycin-impregnated PMMA bone cement; however, clinical data are lacking. In our patient's case, the cement formulation was well tolerated, with no adverse effects detected, and demonstrated adequate mechanical strength in vivo. Infection with P. acnes, an unusual pathogen, was successfully treated. Further clinical studies are required to assess the efficacy of daptomycin-impregnated cement in infection with more typical pathogens, such as S. aureus. Daptomycin impregnation of PMMA bone cement may be an option in cases in which patient or pathogen factors preclude use of routinely incorporated agents.

Contemporary epidemiology and prognosis of septic shock in infective endocarditis

The prognosis of patients with infective endocarditis (IE) remains poor despite the great advances in the last decades. One of the factors closely related to mortality is the development of septic shock (SS). The aim of our study was to describe the profile of patients with IE complicated with SS, and to identify prognostic factors of new-onset SS during hospitalization. We conducted a prospective study including 894 episodes of IE diagnosed at three tertiary centres. A backward logistic regression analysis was undertaken to determine prognostic factors associated with SS development. Multivariable analysis identified the following as predictive of SS development: diabetes mellitus [odds ratio (OR) 2.06; confidence interval (CI) 1.16-3.68], Staphylococcus aureus infection (OR: 2.97; CI: 1.72-5.15), acute renal insufficiency (OR: 3.22; CI: 1.28-8.07), supraventricular tachycardia (OR: 3.29; CI: 1.14-9.44), vegetation size ≥15 mm (OR: 1.21; CI: 0.65-2.25), and signs of persistent infection (OR: 9.8; CI: 5.48-17.52). Risk of SS development could be stratified when combining the first five variables: one variable present: 3.8% (CI: 2-7%); two variables present: 6.3% (CI: 3.2-12.1%); three variables present: 14.6% (CI: 6.8-27.6%); four variables present: 29.1% (CI: 11.7-56.1%); and five variables present: 45.4% (95% CI: 17.5-76.6%). When adding signs of persistent infection, the risk dramatically increased, reaching 85.7% (95% CI: 61.2-95.9%) of risk. In patients with IE, the presence of diabetes, acute renal insufficiency, Staphylococcus aureus infection, supraventricular tachycardia, vegetation size ≥15 mm, and signs of persistent infection are associated with the development of SS.

Survival of a Patient With Trauma-Induced Mucormycosis Using an Aggressive Surgical and Medical Approach

Mucormycosis is a deadly angioinvasive fungal infection that is increasing in incidence. Gastrointestinal and abdominal involvement is rare, has higher mortality rates, and is frequently diagnosed late. We report a patient who sustained multiple gunshot wounds to the chest and abdomen and subsequently developed omental and hepatic mucormycosis. He underwent 14 abdominal washouts and several liver debridements, and he received combination therapy with amphotericin B and micafungin. The patient survived the disease, with negative cultures and pathology at the last washout, and underwent skin grafting. He is clinically improved and remains on oral antifungals as an outpatient. Mucormycosis should be considered in trauma patients with persistent signs of infection after lavage and antibiotics, especially when necrosis or atypical wound presentations are noted. Approaches such as ours using aggressive surgical management and intensive antifungal administration should be instituted once the diagnosis is suspected.

Antibiotic treatment can be safely stopped in asymptomatic patients with prosthetic joint infections despite persistent elevated C-reactive protein values

Prosthetic joint infection should be treated for a prolonged time (3 months for hip, 6 months for knee infection). Most authors require normalization of CRP before stopping antimicrobial therapy. However, in some patients the CRP values remain slightly elevated despite adequate treatment. We observed 14 patients with prosthetic joint infection (6 knee, 9 hip infections), in whom the CRP values never fell below the upper limit of normal. Eleven patients were surgically treated with débridement and retention of the prosthesis, in one patient one-staged reimplantation and in two patients two-staged reimplantations were performed. Antibiotic treatment was stopped according the guidelines, if the patient was clinically without signs of persistent infection and the CRP values reached a plateau, albeit above the cut-off (5 mg/L). All patients were followed for 2 years after primary diagnosis of infection. Only one patient developed a periprosthetic infection five months after stopping antibiotic therapy. However, the isolated pathogen was different from that of the patient's first infection, so we postulate a reinfection rather than a relapse. All other patients remained free of infection for the observed period. Antibiotic treatment can safely be stopped in patients with prosthetic joint infection, even if CRP is not normalized, given that there are no clinical signs of persistent infection and a plateau of CRP level is obtained.

Comprehensive phenotypic characterization of ABCB4 deficient mice reveals systemic effects of spontaneous biliary fibrosis

Aims: ABCB4 deficiency in humans causes or contributes to chronic cholestatic liver diseases. The progression of liver diseases related to ABCB4 deficiency and their systemic effects differ significantly between individuals, yet the genetic factors contributing to these mechanisms are unknown. Our aim now was to phenotypically characterize immune and extrahepatic phenotypes in a genetically defined model of spontaneous biliary fibrosis. Methods: We generated congenic mice by introgressing the Abcb4 knockout from the FVB/NJ strain into the fibrosis-susceptible BALB/cJ background for 10 generation. At the age of 16 weeks, 20 female and 20 male BALB-Abcb4-/- mice and 40 wild-type control mice (BALB/cJ) were phenotyped in standardized, comprehensive workflows (German Mouse Clinic. Nat Methods 2005;2: 403). Results: Clinical-chemical data displayed elevated serum liver enzymes (ALT, AST, AP) in Abcb4-/- mice, whereas serum lipid levels (triglycerides, free fatty acid, cholesterol) were significantly decreased. Erythrocytes displayed a mild hypochromic and microcytic differentiation, whereas white blood cell counts were elevated. Of note, FACS analysis of leukocytes revealed a lower proportion of granulocytes and a higher proportion of T-lymphocytes in Abcb4-/- mice. Detailed analysis of CD4+ and CD8+ T- lymphocytes in peripheral blood showed significant differences of distinct subpopulations, e.g. levels of Ly6C+ CD44+ CD25- cells were decreased and levels of Ly6C- CD44+ CD25- CD4+ cells were increased, whereas CD8+ cells displayed inverse alterations. Conclusions: Comprehensive phenotypic characterization of BALB-Abcb4-/- deficient mice identified systemic alterations of peripheral blood and immune cell populations. Since we did not observe signs of persistent infection, these changes are likely to reflect the systemic immune response to chronic cholestatic liver injury in this mouse model. Supported by NGFN German Mouse Clinic

Management of pelvic abscess after Le Fort colpocleisis

We report the case of a 75-year-old woman who developed pelvic abscess following Le Fort colpocleisis. After drainage and completion of treatment with intravenous antibiotherapy, the patient returned with persistent signs of infection, which responded to outpatient gentamicin irrigation through Le Fort vaginal tunnels.

Surgical versus Nonsurgical Treatment of Empyema Thoracis: An Outcomes Analysis

Empyema thoracis (ET) is associated with substantial morbidity and mortality. The optimal means for draining the pleural space remains controversial but there may be increasing bias for less invasive strategies. This study compared outcome after a nonsurgical versus a surgical approach to ET. Patients with ET over a 10-year period (n = 93) were reviewed and stratified into nonsurgical (thoracentesis and/or closed tube thoracostomy) and surgical (thoracotomy, decortication, and/or open window thoracostomy) groups based on pleural drainage techniques. Hospital course was analyzed except when altered by death (n = 12), noncompliance (n = 3), or severe comorbidities (n = 3). Seventy-five patients were stratified into nonsurgical (n = 32) and surgical (n = 43) groups. Demographics, comorbidities, signs and symptoms, and causative organisms were similar between groups. Mortality did not significantly differ in nonsurgical (16%) versus surgical (10%) groups (P = 0.7). Although delay in diagnosis and number of therapeutic interventions were nearly identical, the time to definitive therapy was longer in the surgical versus the nonsurgical group (18 +/- 3.8 versus 8.5 +/- 3.8 days, P = 0.023). The time to discharge after definitive therapy (20.0 +/- 3.5 versus 35.6 +/- 14.0 days, P < 0.001), and overall hospital stay (40.6 +/- 5.3 versus 47.4 +/- 15 days, P = 0.01) was significantly decreased in the surgical versus nonsurgical treatment groups, respectively. The treatment of ET is complex. Failure to adequately evacuate the pleural space and/or persistent signs of infection should prompt surgical intervention. Surgical therapy is preferred for advanced stages of ET. Delaying definitive surgical treatment is largely responsible for prolonging hospital course.

Periannular extension of infective endocarditis

ObjectivesThis prospective study was designed to assess the current clinical course, risk factors, microbiologic profile and echocardiographic findings of patients with left-sided endocarditis and perivalvular complications. BackgroundPeriannular complications worsen the prognosis of patients with endocarditis. The relation between these complications and the clinical and microbiologic data has not been clearly defined. MethodsIn this clinical cohort study, 211 patients with left-sided endocarditis, according to the Duke criteria, were prospectively recruited. All patients underwent conventional and transesophageal echocardiography. The mean follow-up interval was 151 days. ResultsPerivalvular complications were detected in 78 patients (37%). The incidence of periannular extension of infection in native and prosthetic valves was 29% and 55%, respectively. The presence of prosthesis (relative risk [RR] 1.88, 95% confidence interval [CI] 1.35 to 2.64) and previous endocarditis (RR 1.78, 95% CI 1.16 to 2.7) were the only pre-existing heart conditions associated with perivalvular complications. Aortic infection (RR 1.8, 95% CI 1.23 to 2.66) and the development of atrioventricular (AV) block (RR 2.55, 95% CI 1.91 to 3.41) were related with the existence of these complications. Coagulase-negative staphylococci were very common in patients with perivalvular complications (RR 1.77, 95% CI 1.21 to 2.59), and small vegetations were more frequent in these patients (RR l.45, 95% CI 0.95 to 2.22). An operation was more frequently performed in patients with perivalvular complications, but mortality was similar in patients with and without these complications. ConclusionsAortic infection, prosthetic endocarditis, new AV block and coagulase-negative staphylococci were independent risk factors of periannular complications. The period between symptom onset and diagnosis, the incidence of pericardial effusion and persistent signs of infection were similar between patients with and without perivalvular complications. Patients with perivalvular complications did not demonstrate a difference in the presence or size of vegetations or the frequency of embolism. An operation was more frequently performed in these patients, but mortality was similar in both groups.