Severe Bacterial Infections In Patients Research Articles

Pretreatment Lymphopenia, Poor Performance Status, and Early Courses of Therapy Are Risk Factors for Severe Bacterial Infection in Patients with Multiple Myeloma during Treatment with Bortezomib-based Regimens.

The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0.001), early course of therapy (≤ 2 courses, P < 0.001), and pretreatment lymphopenia (absolute lymphocyte count < 1.0 × 109/L, P = 0.043) were confirmed as independent risk factors. The probability of developing SBI were 5.1%, 14.9%, 23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). In conclusion, we identified three pretreatment risk factors associated with SBI in each course of bortezomib treatment. Therefore, MM patients with these risk factors should be more closely monitored for the development of SBI during bortezomib-based treatment.

Severe bacterial infections in patients with non-transfusion-dependent thalassemia: prevalence and clinical risk factors

Bacterial infection is one of the major causes of death in patients with thalassemia. Clinical predictive factors for severe bacterial infection were evaluated in patients with non-transfusion-dependent thalassemia (NTDT). A retrospective study was conducted of patients with NTDT aged ≥ 10 years at Srinagarind Hospital, Khon Kaen University, Thailand. Clinical characteristics and potential clinical risk factors for bacterial infection were collected. Risk factors for bacterial infection were evaluated by multivariate logistic regression analysis. A severe bacterial infection was found in 11 of the total 211 patients with NTDT (5.2%). None of the clinical factors assessed was shown to be statistically associated with severe bacterial infection in patients with NTDT. However, three factors were demonstrated to be potential predictive factors for severe bacterial infection: time after splenectomy >10 years, deferoxamine therapy, and serum ferritin >1000 ng/ml. None of the patients died from infection. The prevalence of bacterial infection in patients with NTDT was found to be moderate. Time after splenectomy >10 years, deferoxamine therapy, and iron overload may be clinical risk factors for severe bacterial infection in patients with NTDT. Bacterial infection should be recognized in splenectomized patients with NTDT, particularly those who have an iron overload.

Pretreatment Lymphopenia and Poor Performance Status are Risk Factors of Severe Bacterial Infection in Patients with Multiple Myeloma During Chemotherapy with Bortezomib-Containing Regimens

ABSTRACT Aim: Infection is the leading cause of morbidity and mortality in patients with multiple myeloma. The aim of this study is to identify the risk factors associated with the development of severe infections in patients with multiple myeloma during chemotherapy with bortezomib-containing regimens. Methods: A total of 98 patients with myeloma who were treated with bortezomib-based chemotherapy between 2006 and 2012 were examined. Using the logistic regression method, a variety of factors were analyzed for the development of severe bacterial infections (SBI) at each of 427 courses. Results: Median age of patients was 62 years, and 40.6% (30/98) of patients were treated with bortezomib-containing chemotherapy as first-line treatment. The SBI was developed in 57% (56/98) of patients and 19% (81/427) of bortezomib courses. Of 81 SBI episodes, 42 (53%) episodes were clinically documented infection, 30 (37%) episodes were microbiologically documented infections, and 9 (11%) episodes were fever of unknown origin. Multivariate logistic regression analysis revealed poor performance status (ECOG ≥2) (HR 3.920, 95% C.I. 2.305-6.666, P Conclusions: Patients with these risk factors (early courses of therapy, poor performance status and lymphopenia) should be more closely monitored for bacterial infections and a consideration of prophylactic use of antibiotics at least for the initial 2 courses of therapy would be helpful to decrease bacterial infections. Disclosure: All authors have declared no conflicts of interest.

Risk factors for severe bacterial infections in patients with systemic autoimmune diseases receiving rituximab

The risk of serious bacterial infectious events (SIEs) after an RTX course used in severe and refractory cases of systemic autoimmune diseases (SAID) is well known. Risk factors for SIEs merit investigation. For this case–control study, data were collected in a single centre of internal medicine and included all patients who received rituximab (RTX) for SAID between 2005 and 2011 (rheumatoid arthritis was excluded). Sixty-nine patients with SAID received a total of 87 RTX courses. Thirteen SIEs were reported in 12 patients leading to death in 5 patients. Patients with a history of SIE were significantly older (63.6 ± 18.8 vs 48.8 ± 16.7; p = 0.0091), suffered most frequently of diabetes mellitus (33.3 % vs 5.3 %, p = 0.015), had a lower CD19 count (1.0 ± 1.2/mm3 vs 3.9 ± 7.2/mm3) and had most frequently a prednisone dose >15 mg/day (91.7 % vs 47.7 %) at the start of the first RTX course. The SIE rate was 18.7 per 100 patient-years. At the initiation of the RTX course, risk factors for SIEs were lower IgG levels (OR = 0.87, 95%CI = 0.77–0.99, p = 0.03), lower CD19 count (OR = 0.85, 95%CI = 0.73–1.00) and creatinine clearance ≤ 45 ml/min (OR = 7.78, 95%CI = 1.36–44.38, p = 0.002). Conversely history of pneumococcal vaccination significantly decreased the risk of SIEs (OR = 0.11, 95%CI = 0.03–0.41, p = 0.0009). Concomitant treatment with prednisone at a dose >15 mg/day significantly increased the SIE risk (OR = 8.07, 95%CI = 1.94–33.59, p = 0.0004). SIEs are frequent in SAID treated with RTX, particularly in patients receiving high-dose corticosteroids, in patients with renal insufficiency and in patients with low IgG levels or a low CD19 count.

Genetic variation in TNFA predicts protection from severe bacterial infections in patients with end-stage liver disease awaiting liver transplantation

Augmented susceptibility to infections increases mortality in patients with end-stage liver disease (ESLD). We sought to determine the contribution of selected genetic variants involved in inflammatory signalling downstream of the Toll-like receptor 4 (TLR4) to severe bacterial infections (SBIs) in patients with ESLD. We retrospectively assessed incidence of SBIs in 336 adult ESLD patients enlisted for orthotopic liver transplantation (OLT) and genotyped them for TLR4 c.+1196C/T, CD14 c.-159C/T, TNFA c.-238G/A, TNFA c.-863C/A, IL1B c.-31C/T and IL1RN variable number of tandem repeats allelic variants. Principal findings were validated in an independent cohort of 332 ESLD patients. Thirty-four percent of patients from the identification cohort and 40% of patients from the validation cohort presented with SBI while enlisted for OLT. The presence of the variant allele TNFA c.-238A (rs361525) was associated with lower serum levels of TNF-α, and with significantly decreased risk of SBI in both cohorts. Multivariate analysis showed that the relative protection from SBI associated with this allele almost completely negated the increased susceptibility to SBI owed to advanced ESLD. Although not predictive of overall mortality, the presence of the TNFA c.-238A allele was associated with a complete prevention of SBI-related pre-transplant deaths. Our results suggest that genetic variability in inflammatory signalling is associated with the development of SBI in patients with ESLD. Specifically, we identified the importance of the TNFA c.-238A allele as a strong predictor of protection from SBI, and as a genetic marker associated with significantly improved pre-transplant survival in patients with SBI.

Risk Factors For The Development Of Severe Bacterial Infection In Patients With Multiple Myeloma During Chemotherapy With Bortezomib Containing Regimens

BackgroundThe aim of this study is to identify risk factors associated with the development of severe bacterial infection (SBI) in patient with multiple myeloma (MM) during treatment with bortezomib-containing regimens. MethodsA total of 98 patients with MM who were treated with bortezomib-based treatment between 2006 and 2012 were analyzed. Fifty three patients received bortezomib-dexamethasone, 25 patients received bortezomib-melphalan-prednisolone, 15 patients received bortezomib-doxorubicin-dexamethasone and 5 patients received other regimens. They received a total of 427 courses of treatment. The SBI was defined as at least grade 3 neutropenic/non-neutropenic infection by NCI Common Terminology Criteria for Adverse Events version 4.0. Using the logistic regression method, we analyzed risk factors for the development of SBI during each course of treatment. ResultsMedian age of the patients was 62 years and 40.6% (30/98) of patients treated with bortezomib-containing regimens as first-line therapy. The SBI was developed in 57% (56/98) of patients and 19% (81/427) of bortezomib courses. Among 81 episodes of SBI, 42 (53%) episodes were clinically documented infection, 30 (37%) were microbiologically documented infections, and 9 (11%) were fever of unknown origin. The most common type of infection was pneumonia (60%). Poor performance status (ECOG ≥2) (Hazard Ratio [HR] 5.365, 95% Confidence Interval [CI] 2.004-14.364, P =.001) was the only risk factor for the development of SBI in 98 patients. When we analyzed the risk factors for the development of SBI which occurred during each treatment course, poor performance status (ECOG ≥2) (P <.001), early course of treatment (≤2 courses) (P <.001) and pretreatment lymphopenia (absolute lymphocyte count <1.0 x 109/L) (P = .043) were associated with increased risk for developing SBI in each course. These 3 risk factors remained independently significant in multivariate analysis: poor performance status (ECOG ≥2) (HR 3.920, 95% CI 2.305-6.666, P <.001), early course of treatment (≤2 courses) (HR 2.782, 95% CI 1.633-4.740, P <.001) and pretreatment lymphopenia (HR 1.728, 95% CI 1.016-2.937, P = .043). The probability of developing SBI in each treatment course was 5.1% in courses with no risk factor, 14.9% in 1 risk factor, 23.9% in 2 risk factors and 59.5% in 3 risk factors (P <.001, Figure 1). After treatment with bortezomib-containing regimens, patients who experienced SBI showed a significantly shorter overall survival than patients who didn't experienced SBI (median 6.1 month vs. 30.1 months, P = .004) although progression free survival was not different (median 18.1 months vs. 21.9 months, P = .418). The multivariate cox analysis demonstrated that the development of SBI was associated with inferior overall survival (HR 2.440, 95% CI 1.305-4.561, P = .005) as well as male sex (HR 2.323, 95% CI 1.236-4.367, P = .009). ConclusionsIn conclusion, we identified that poor performance status, early courses of treatment, and lymphopenia at the beginning of each treatment course were the risk factors for the development of SBI in patients with MM during treatment with bortezomib-containing regimens. Close monitoring for the development of SBI and appropriate treatment should be considered in the patients with risk factors. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Severe Bacterial Infection in Patients with Heterotaxy Syndrome

To determine the incidence of sepsis in patients with heterotaxy syndrome. From our institutional database, we identified patients with heterotaxy syndrome and other complex congenital heart disease (CHD) born between 2001 and 2011. Severe bacterial infection was defined as sepsis with positive culture result or infection with abscess formation. We enrolled 95 patients with heterotaxy syndrome (88 with right atrial isomerism and 7 with left atrial isomerism) and 142 patients with complex CHD. With 1026 person-years follow-up, the 5-year survival was 52% and 65.7% in heterotaxy and complex CHD groups, respectively (P = .239). Community-acquired severe bacterial infection occurred only in heterotaxy syndrome (13 episodes in 10 patients, 3 of whom had spleen noted at imaging study) with 2- and 5 years cumulative severe bacterial infection rate of 9.6% and 14.5%, respectively. The overall mortality rate of those with community-acquired severe bacterial infection was 31%. Pneumococcus and Citrobacter freundii were the most common pathogens. Nosocomial severe bacterial infection occurred in 33.3% of all patients and 12.5% of all procedures. The rates (0.59 and 0.52/100 hospitalization days in heterotaxy and complex CHD group) and the pathogens of nosocomial severe bacterial infection were similar between heterotaxy and complex CHD groups. Patients with heterotaxy syndrome are at high risk for community-acquired severe bacterial infection and also have high mortality rate whether the spleen is present or not. The risk of nosocomial severe bacterial infection seems similar to that of patients with other complex CHD.

Bacteremia in patients receiving TNF-alpha antagonists – A prospective multicenter study

TNF-alpha antagonists have changed the outcome of various chronic inflammatory diseases. Their use has spread widely and many patients receive those treatments for years. Previous reports found that the use of TNF-alpha antagonists may be associated with an increased risk of serious bacterial infections. We report 47 prospective bacteremia cases from the RATIO registry. A national prospective study was conducted in France between 2004 and 2007 to collect severe bacterial infections in patients receiving TNF-alpha antagonists. All reported cases of bacteremia were validated by an expert committee. Forty-seven bacteremic episodes were reported. Staphylococcus aureus represented the most frequent causative pathogen (40%) and was mostly associated with bones and/or joints infections (68%) and with a worse outcome compared to that observed with other bacterial pathogens. Patients receiving TNF-alpha antagonists may develop bacteremia and S. aureus has to be included in the spectrum of the initial empiric antimicrobial therapy.

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Case Reports: This is a 36 year old man with no significant past medical history who presented to a local hospital with several days of prodromal viral symptoms: fevers, chills, cough. During early hospitalization, he quickly decompensated for unknown reasons, developing acute respiratory distress syndrome (ARDS), requiring mechanical ventilation, and transfer to higher level of care for the initiation of extracorporeal membrane oxygenation (ECMO). The patient received veno-venous ECMO for approximately 7 days. During that time, procalcitonin levels were measured daily and trended while the patient required antibiotic therapy, along with temperature and white blood cell (WBC) count. As the patient clinically improved as evident by temperature, WBC count, and hemodynamics, there was a down-trend in his procalcitonin levels. Antibiotics were discontinued after 7 days. During his hospital course, the patient had several episodes of fever associated with increased expectoration. Interestingly, with each subsequent episode of hospital-acquired pneumonia, procalcitonin levels had risen prior to antimicrobial resumption, decreased with antibiotic therapy, and were consistent with fever trends. Discussion: Antibiotic resistance has become an important factor affecting patient outcome in the intensive care unit. With the overuse of broad spectrum antibiotics, we are heading towards extreme drug resistance especially with gram-negative bacilli. Stewardship programs are looking at biomarkers to help guide duration of antibiotics. Procalcitonin is a fairly specific biomarker for severe bacterial infection in patients with suspected sepsis. A strong correlation exists between concentration of procalcitonin and the extent and severity of bacterial infection. By following the levels of procalcitonin, a few studies have already suggested protocols to shorten antibiotic duration. Even in the setting of ECMO-induced cytokine storm, procalcitonin levels seem to remain unaffected by ongoing systemic inflammation. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010; 375: 463-74.

Sa1033 Oral Nutrition With a High Content of BCAA Improves the Liver Function and Major Symptoms of Decompensated Cirrhotic Patients Unresponsive to BCAA Granules Only

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a frequent and severe bacterial infection in patients with decompensated cirrhosis and ascites. Most organisms causing SBP are from intestinal microbial flora with Enterobacteriaceae and Escherichia coli being reported the most common organisms. However, studies of small series in recent years reported increasing frequency of SBP caused by Gram -positive bacteria in SBP. AIM: To evaluate microbial characteristics of ascitic fluid in cirrhotic patients with spontaneous bacterial peritonitis. METHODS: Medical records of 236 patients who underwent diagnostic paracentesis from July 1 2006 to July 1 2011 at Hershey Medical Center were reviewed. Pertinent data were collected and analyzed using SAS 1.1 software. RESULTS: One hundred ninety eight patients, age between 18-80 years old who had cirrhosis and ascites were included. The majority of the patients with end stage liver disease had either alcoholic liver disease or viral hepatitis or both. 145 (73.2%) were males and 53 (26.8 %) were females. Mean age was 54.8 years. Total 650 cultures were performed. 153 out of 650 cultures (23.5%) met criteria of spontaneous bacterial peritonitis based on absolute neutrophil count in ascitc fluid >250 cells/mm3. Bacteria grew in 86 cultures. 21 of the 86 cultures grew 2 or more micro-organisms, possible secondary to contamination, were excluded from this analysis. One culture grew candida. Fifty out of 64 (78.1%) cultures grew Gram-positive bacteria and 14/64 (21.9%) cultures grew Gram-negative bacteria. Most common organism isolated was coagulase negative Staphylococcus and the most common Gram-negative organism isolated was Klebsiella. Positive culture result of either Gram-positive or Gram-negative bacteria did not differ in age, MELD score, frequency of paracentesis, etiology of liver disease, or previous history of SBP. CONCLUSION: Our study shows increased frequency of Grampositive bacteria in patients with SBP which is a change in the pattern of SBP compared to current guideline. Larger prospective studies are needed to confirm this finding. The implication of such change is likely to modify treatment strategies particularly when empiric therapy is contemplated.

Necrotising fasciitis of the shoulder in association with rheumatoid arthritis treated with etanercept: a case report

IntroductionNecrotising fasciitis is a severe infection characterised by the fulminant destruction of tissue with associated systemic signs of sepsis and toxicity. Etanercept is a fully human fusion protein that inhibits tumor necrosis factor and the inflammatory cascade. It is effective in the treatment of many disorders but concerns regarding severe life threatening infections have been raised in multiple reports.Case presentationWe present the case of a 39-year-old Caucasian man, who presented with sudden onset of severe and progressive neck and left shoulder pain, with a two-year history of seronegative rheumatoid arthritis treated with azathoprine and etanercept. On examination the left side of his neck and his left shoulder were oedematous, tender with an erythematous rash and his active range of movement was limited. Magnetic resonance imaging of his shoulder showed extensive oedema of the subcutaneous and intramuscular fat of the left lower neck consistent with fasciitis. He was treated medically and made a good recovery.ConclusionOur patient, while having a pre-existing increased mortality risk, had a serious infection which responded well to optimum medical treatment without the need for surgery. As anti tumor necrosis factor agents are frequently associated with infection, including tuberculous infection, this case highlights the need for a high index of suspicion for other severe bacterial infections in patients on immunosuppressants.

Efficacy of Ceftizoxime in the Treatment of Severe Bacterial Infections in Patients with Cirrhosis

Bacterial infections, particularly spontaneous bacterial peritonitis and bacteraemia, are a frequent complication in cirrhotic patients (Rimola et al. 1986). These infections are predominantly caused by Enterobacteriaceae, although a significant proportion are caused by other organisms, particularly Gram-positive cocci. Even when appropriate treatment is given, spontaneous bacterial peritonitis and bacteraemia in cirrhosis are associated with a high mortality rate. Because of the severity of these infections, antibiotic therapy must be initiated empirically, without any knowledge of causative organisms and their in vitro susceptibility. In a randomised controlled study in the empirical treatment of severe infections in cirrhosis, Felisart et al. (1985) observed that cefotaxime was more effective than ampicillin + tobramycin and concluded that cefotaxime should be considered as the first-choice antibiotic in this situation. However, because of the short halflife of cefotaxime, frequent administration is required (Carmine et al. 1983); in the Felisart study, for example, cefotaxime was administered at a dosage of 2g every 4 hours. In the present investigation we therefore evaluated the efficacy of ceftizoxime, a third generation cephalosporin with a similar antibacterial spectrum to that of cefotaxime but with a more prolonged half-life (Richards & Heel 1985), in a series of cirrhotic patients with severe bacterial infections. Additionally, serum and ascitic fluid ceftizoxime concentrations were determined in these patients.