Immunocompetent Adult Patients Research Articles

Personalized Prophylaxis with Human-Cl Recombinant FVIII in HA Patients

BackgroundProphylactic therapy aims to maintain sufficient factor VIII (FVIII) plasma levels to prevent bleeding. FVIII plasma trough level and time spent above a certain threshold are mainly determined by the half-life of the FVIII concentrate and the injection interval.AimsA clinical study was conducted to investigate the efficacy of individually PK-tailored prophylaxis with Human-cl rhFVIII.MethodsThis prospective, open-label, multicenter phase 3b study included previously treated immunocompetent adult patients with severe hemophilia A without past or present inhibitors. Each patient started with a PK evaluation (single dose of 60 ± 5 IU/kg) followed by 1-3 months of routine prophylaxis (i.e. 30-40 IU/kg every other day or 3 times per week, Phase I) until individual PK data was analyzed. It was calculated, which dose and injection interval would theoretically result in a trough FVIII level of ≥1%. Then, prophylaxis was continued for 6 months using the individually recommended treatment scheme (Phase II).ResultsThe study enrolled 66 patents from 20 centers across 8 countries. The majority of patients (62.1%) had been treated on-demand only before study entry. Their median annualized bleeding rate (ABR) was 41. Key outcomes of the personalized prophylaxis are: •The prophylactic injection interval was extended from usually 3 times per week in Phase-I to twice per week or less in 58% of patients.•The median dosing interval was 3.5 days.•73% of patients did not experience any bleeding episode.•The mean ABR in phase-II was 1.45 (3.16 in Phase-I).•The median weekly prophylactic dose decreased by nearly 10% compared to Phase-I.•There were no inhibitors and related serious adverse events.ConclusionThe data suggest that personalized prophylaxis with Human-cl rhFVIII results in a more convenient treatment for more than half of the patients with lower factor consumption and a lower ABR while remaining safe and efficacious. DisclosuresKlamroth:Biogen and SOBI: Honoraria, Speakers Bureau; Bayer, Baxter, CSL Behring, Pfizer, Novo Nordisk, and Octapharma: Honoraria, Research Funding, Speakers Bureau. Rusen:Octapharma: Other: Investigator. Walter:Octapharma: Employment. Bichler:Octapharma AG: Employment. Pasi:Biogen, Octapharma, Genzyme, and Pfizer: Consultancy, Honoraria; Octapharma: Research Funding. Tiede:Octapharma: Other: Investigator, Speakers Bureau; Leo Pharma: Consultancy, Honoraria; SOBI: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Biogen Idec: Consultancy, Honoraria; Biotest: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Investigator, Research Funding; Baxter: Consultancy, Honoraria, Research Funding; Coachrom: Research Funding. Knaub:Octapharma: Employment.

Annual incidence rates of herpes zoster among an immunocompetent population in the United States.

BackgroundHerpes zoster (HZ), also known as shingles, is a painful and commonly occurring condition in the United States. In spite of a universally recommended vaccine for use in immunocompetent adults aged 60 years and older, HZ continues to impact the American public, and a better understanding of its current incidence is needed. The objective of the current study is to estimate the overall and age- and gender-specific incidence rates (IRs) of HZ among an immunocompetent US population in 2011 following availability of a vaccine.MethodsClaims data from the Truven Health MarketScan® Research databases between 01/01/2011 and 12/31/2011 were extracted. Immunocompetent adult patients, enrolled as of January 1, 2011 were analyzed. The denominator was defined as eligible subjects who were immunocompetent, had no evidence of zoster vaccination, and no diagnosis of HZ (International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 053.xx) in the 90 days prior to January 1, 2011. Subjects contributed person-days to the denominator until the occurrence of one of the following events: end of continuous enrollment in the database, a claim for zoster vaccination, diagnosis of HZ or end of the observation period (December 31, 2011). The numerator was defined as enrollees within the denominator file exhibiting evidence of HZ. Annual IRs were calculated for the entire population in the database as well as by gender and age group; standardized IRs were also produced using the 2010 US Census data.ResultsThe overall annual IR of HZ across all ages was 4.47 per 1000 person-years (95 % confidence interval [CI]: 4.44–4.50) which monotonically increased with age from 0.86 (95 % CI: 0.84–0.88) for those aged ≤19 to 12.78 (95 % CI: 12.49–13.07) for patients ≥80 years. The IR was 8.46 (95 % CI: 8.39–8.52) among adults ≥50 years and 10.46 (95 % CI: 10.35–10.56) among those aged ≥60 years. Women compared to men had higher HZ incidence (5.25, 95 % CI: 5.21–5.29 vs. 3.66, 95 % CI: 3.62–3.69) and this was seen across all age groups. When adjusted for age and gender using 2010 US Census data, the annual IR was 4.63 per 1000 person-years (95 % CI: 4.61–4.66).ConclusionsDespite the availability of a vaccine, HZ remains common among immunocompetent adults in the US with incidence rates of HZ observed to increase with age and be higher in women than men.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1262-8) contains supplementary material, which is available to authorized users.

RARE-13HYPERACUTE ADVERSE EVENTS OF HIGH-DOSE METHOTREXATE MONOTHERAPY IN PRIMARY CNS LYMPHOMA PATIENTS

OBJECTIVES: High-dose methotrexate chemotherapy (HD-MTX) is the mainstay in treatment of primary CNS lymphoma (PCNSL) and has been known to have acute or late toxicity on skin, gastrointestinal mucosa, liver, kidneys, and bone marrow. However, hyperacute adverse events (HADE), which occurred within one hour of HD-MTX administration, are rarely known in PCNSL patients. We report our HADE experiences with 9 consecutive cases. METHODS: Of 51 PCNSL patients, 38 immunocompetent adult PCNSL patients treated with HD-MTX at Seoul St. Mary's Hospital, The Catholic University of Korea between 2004 and 2015 were investigated. Our HD-MTX monotherapy regimen consists of induction period (8 g/m2 on day 1, 10, and 20 for 3 cycles) and maintenance period (3.5 g/m2, every 4 weeks for 3 cycles and then every 3 months for 3 cycles). Medical records were reviewed for each of the HADE events, retrospectively. RESULTS: Of 38 patients who received HD-MTX of 247 cumulative cycles, 9 patients (23.7%; 4 men and 5 women) presented 13 HADE. Median age of the patients was 58 years (range 47 to 64 years) at the time of the event. HADE developed during the maintenance period in 5 patients, at the early induction period in 1 patient and at the rechallenging period for recurrence in 3 patients. HADE symptoms were variable; most commonly skin rashes in 12 events (92.3%), abdominal pain in 2 events (15.4%), and most severely hypotension in 1 event (7.7%). HD-MTX monotherapy was discontinued in 4 patients, continued with corticosteroid premedication and symptomatic application of antihistamine with or without MTX dose modification in 5 patients, and completed in 2 patients. CONCLUSION: Although HD-MTX appears to be a relatively safe medication, greater awareness of possible HADE in HD-MTX chemotherapy is needed for its prevention, early diagnosis and management. Studies to clarify its mechanism should be warranted.

Clinical predictors of bacteremia in immunocompetent adult patients hospitalized for community-acquired pneumonia

The clinical usefulness of blood cultures in the management of patients hospitalized with community-acquired pneumonia (CAP) is controversial. To determine clinical predictors of bacteremia in a cohort of adult patients hospitalized for community-acquired pneumonia. A prospective cohort of 605 immunocompetent adult patients aged 16 to 101 years (54% male) hospitalized for CAP was studied. The clinical and laboratory variables measured at admission were associated with the risk of bacteremia by univariate and multivariate analysis using logistic regression models. Seventy seven percent of patients had comorbidities, median hospital stay was 9 days, 7.6% died in hospital and 10.7% at 30 days. The yield of the blood cultures was 12.6% (S. pneumoniae in 69 patients, H. influenzae in 3, Gram negative bacteria in three and S. aureus in one). These results modified the initial antimicrobial treatment in one case (0.2%). In a multivariate analysis, clinical and laboratory variables associated with increased risk of bacteremia were low diastolic blood pressure (Odds ratio (OR): 1.85, 95% confidence intervals (CI) 1.02 to 3.36, p < 0.05), leukocytosis e" 15,000/mm³ (OR: 2.18, 95% CI 1.22 to 3.88, p < 0.009), serum urea nitrogen e" 30 mg/dL (OR: 2.23, 95% CI 1.22 to 4.05, p < 0.009) and serum C-reactive protein e" 30 mg/dL (OR: 2.20, 95% CI 1.22 to 3.97, p < 0.01). Antimicrobial use before hospital admission significantly decreased the blood culture yield (OR: 0.14, 95% CI 0.04 to 0.46, p < 0.002). Blood cultures do not contribute significantly to the initial management of patients hospitalized for community-acquired pneumonia. The main clinical predictors of bacteremia were antibiotic use, hypotension, renal dysfunction and systemic inflammation.

Whole-Genome Sequence of Listeria monocytogenes Serovar 4b Strain IZSAM_Lm_hs2008, Isolated from a Human Infection in Italy.

Listeria monocytogenes is one of the most important foodborne pathogens. In this report, we present the complete and annotated genome of L. monocytogenes sequence type 06 (ST06) serovar 4b strain IZSAM_Lm_hs2008, isolated from an adult immunocompetent patient who developed the disease and died.

Year in review 2014: Lung cancer, pleural diseases, respiratory infections and tuberculosis, bronchoscopic intervention and imaging.

Year in review 2014: Lung cancer, pleural diseases, respiratory infections and tuberculosis, bronchoscopic intervention and imaging.

Community-acquired necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus ST30-SCCmecIVc-spat019-PVL positive in San Antonio de Areco, Argentina

Community-acquired methicillin-resistant Staphylococcus aureus is the first cause of skin and soft tissue infections, but can also produce severe diseases such as bacteremia, osteomyelitis and necrotizing pneumonia. Some S. aureus lineages have been described in cases of necrotizing pneumonia worldwide, usually in young, previously healthy patients. In this work, we describe a fatal case of necrotizing pneumonia due to community-acquired methicillin-resistant S. aureus clone ST30-SCCmecIVc-spat019-PVL positive in an immunocompetent adult patient.

Community-Acquired Pneumonia and Empyema Caused by Citrobacter koseri in an Immunocompetent Patient.

Citrobacter species, belonging to the family Enterobacteriaceae, are environmental organisms commonly found in soil, water, and the intestinal tracts of animals and humans. Citrobacter koseri is known to be an uncommon but serious cause of both sporadic and epidemic septicemia and meningitis in neonates and young infants. Most cases reported have occurred in immunocompromised hosts. The infections caused by Citrobacter are difficult to treat with usual broad spectrum antibiotics owing to rapid generation of mutants and have been associated with high death rates in the past. We believe this is the first case described in the literature of a community-acquired pneumonia and empyema caused by Citrobacter koseri in an immunocompetent adult patient.

Treatment Outcomes with Nitazoxanide in Immunocompetent Adults Naive Patients with Cryptosporidiosis; Do We Need Combination Therapy with Paromomycin or Azithromycin?

Introduction: Human cryptosporidiosis is caused by infection with Cryptosporidium. Nitazoxanide has shown activity against cryptosporidium. The objective of this study is to see treatment outcomes with 7 days of nitazoxanide in immunocompetent adult patients diagnosed with cryptosporidiosis and to consider combination therapy which includes nitazoxanide with paromomycin or azithromycin? Study Design: This cross sectional study was conducted at Sindh Institute of Urology and Transplantation, Karachi Pakistan. Patients were not enrolled with prior diagnosis of cryptosporidiosis and/or had taken Nitazoxanide, Paromomycin or Azithromycin in last 4 weeks prior their diagnosis. Also patients were excluded if they were diagnosed as case of HIV/AIDS, history of solid organ transplantation, any malignancy or were taking steroids and immunosuppressant drugs. Results: A total of 58 patients who had cryptosporidiosis were included in this study. 31 (53.4%) were males and 27 (46.6%) females. The mean age was 33.4 years with standard deviation ± 9.2. No statistical significance was seen in clinical presentation of cryptosporidiosis in both male and female genders. All 58 (100%) reported resolution of diarrhea after 7 days of nitazoxanide treatment. However, at 6 weeks follow up, 40 (70.1%) patients had recurrence of diarrhea whereas only 17 (29.9%) had no further episode of diarrhea. Conclusion: Nitazoxanide is a new nitrothiazole compound with broadspectrum activity against numerous intestinal protozoa and helminths and have very good bio-safety profile. All 58 patients after 7 days of treatment with nitazoxanide showed good clinical response after short term. But in long term patients reported a high recurrence in 6 weeks period time. There is need of combination therapy which includes nitazoxanide with paromomycin or azithromycin in high recurrence/relapse patients.

Clinical presentation and risk factors for cytomegalovirus colitis in immunocompetent adult patients.

Cytomegalovirus (CMV) colitis is a common manifestation of CMV end-organ disease, which has typically been described in immunocompromised hosts. Recently, it has been noted that this also occurs in immunocompetent patients. To gather relevant data about clinical presentation, prognosis, and risk factors for development of CMV colitis in immunocompetent hosts, we analyzed all cases that occurred during a 19-year period at our institution. A case-control study was performed to identify risk factors for CMV colitis in immunocompetent hosts. Electronic medical records of individuals who were admitted and diagnosed with CMV colitis between January 1995 and February 2014 at a tertiary care university hospital were reviewed. Two non-CMV colitis patients who were age- and sex-matched were selected as controls for each case. A total of 51 patients with CMV colitis were included in this study along with 102 control patients. Certain conditions including renal disease on hemodialysis, neurologic disease, rheumatologic disease, intensive care unit admission, and exposure to antibiotics, antacids, steroids, or red blood cell (RBC) transfusions within 1 month of diagnosis of colitis were associated with CMV colitis on univariate analysis. Among these, steroid use and RBC transfusion within 1 month were identified as independent risk factors for developing CMV colitis on multivariate analysis. The 30-day mortality rate was 7.8% without any attributable mortality. Steroid use and RBC transfusion within 1 month of the diagnosis of colitis were independent risk factors for development of CMV colitis in immunocompetent hosts.

1167Clinical Presentation and Risk Factors for Cytomegalovirus Colitis in Adult Immunocompetent Patients

1167Clinical Presentation and Risk Factors for Cytomegalovirus Colitis in Adult Immunocompetent Patients

Presence of human cytomegalovirus DNA in blood of patients with community-acquired pneumonia

After a primary infection, human cytomegalovirus (HCMV) remains latent in certain human cells. Different stimuli, including immune deficiency and severe infection, can trigger the reactivation of latent HCMV infection. In the last decade, the role of the reactivation in immunocompetent patients with serious illness has been intensely studied; however, the knowledge of the potential role of moderately severe infections on HCMV dynamics is limited. In the prospective study, 80 HCMV-seropositive, immunocompetent adult patients with community-acquired pneumonia (CAP), treated outside the intensive care unit (ICU), were monitored with real-time polymerase chain reaction (PCR) for the presence of HCMV DNA. Detection of HCMV DNA in whole blood and/or plasma was interpreted as reactivation of latent HCMV infection. HCMV DNA was detected in 6 of 80 (7.5%) patients. All HCMV DNA–positive patients were classified according to the pneumonia severity index (PSI) as high-risk classes IV or V; thus, HCMV DNAaemia rate within these two PSI classes was 16.7%. All of the patients had positive whole blood samples, whereas plasma samples were positive in a single patient. We did not detect any significant differences comparing six patients with proven HCMV DNAaemia and 74 patients in whom HCMV DNAaemia was not demonstrated regarding the levels of inflammatory parameters on admission, length of treatment with supplemental oxygen, and length of hospital stay. In conclusion, the finding of HCMV DNAaemia in patients with CAP treated outside the ICU is a rare event and occurs only in patients with PSI classes designating more severe pneumonia.

Evaluation of Pulmonary and Extrapulmonary Tuberculosis in Immunocompetent Adults: A Retrospective Case Series Analysis

Objective: It was the aim of this study to evaluate the demographic factors and clinical features of extrapulmonary tuberculosis (EPTB) compared to those of pulmonary tuberculosis (PTB) among adult immunocompetent patients. Subjects and Methods: A total of 427 patients with clinically, radiologically and histopathologically confirmed TB were enrolled in the study, in our clinic at a tertiary care hospital in Turkey, during a 5-year period (2007-2012). Patient data were obtained retrospectively. Among the 427 patients, 55 patients with both PTB and EPTB and who were using steroids or had taken immunosuppressive drugs were excluded from the study. Results: Of the 372 patients, 227 (61%) were males and 168 (45.2%) had EPTB; 204 (54.8%) patients had PTB. The most frequent sites of EPTB were the lymph nodes (n = 45, 12.1%), pleura (n = 40, 10.7%) and brain (n = 7, 1.8%). The most common symptoms were cough (n = 174, 46.7%), night sweats (n = 127, 34.1%) and fever (n = 123, 33%). Compared to EPTB patients, PTB patients were less likely to have received Bacillus Calmette-Guérin vaccination (odds ratio 0.41, 95% confidence interval 0.2-0.63; p < 0.001). Eighty-one (48.2%) of the EPTB and 146 (71.6%) of the PTB patients were males. Pulmonary involvement was more common among men (n = 146, 71.6%) than among women (n = 58, 28.2%; p = 0.000). Conclusion: There was a high incidence of EPTB in our study. Early diagnosis of EPTB is crucial for treatment, and atypical presentations of TB should be kept in mind for immunocompetent patients living in endemic areas. Females especially should be investigated for EPTB.

Streptococcus pneumoniae antigen in urine: Diagnostic usefulness and impact on outcome of bacteraemic pneumococcal pneumonia in a large series of adult patients

Urinary pneumococcal antigen detection provides good results in the diagnosis of pneumococcal pneumonia but has rarely been used in bacteraemic pneumococcal pneumonia and it is not known whether it is associated with outcome in this type of pneumonia. Our objectives were to assess the usefulness of an immunochromatographic technique for detecting the pneumococcal antigen in urine in a large prospective study of patients with bacteraemic pneumococcal pneumonia and explore any potential association with outcomes. This study, carried out over 8 years, included all adult immunocompetent patients admitted for bacteraemic pneumococcal pneumonia. An immunochromatographic test for the Streptococcus pneumoniae antigen in urine was performed in the first 24 h. The sensitivity of test was assessed and patients were divided into two groups according to test results to explore differences on admission and during the course of the illness using logistic regression models. Of the 350 patients with bacteraemic pneumococcal pneumonia included, 261 (74.6%) were positive for the antigen. Patient characteristics were very similar on admission and differences in severity (Pneumonia Severity Index) were not statistically significant. In the adjusted analysis, antigen-positive patients had a higher risk of intensive care unit admission, treatment failure and adverse outcome. The sensitivity of the immunochromatographic urinary antigen test was 74.6% and positive results were associated with poorer clinical outcome. We therefore recommend systematic use of this test when pneumonia is diagnosed in the emergency department.

Primary central nervous system lymphoma with preceding spontaneous pseudotumoral demyelination in an immunocompetent adult patient: A case report and literature review.

The rapid disappearance of primary central nervous system lymphomas (PCNSL) following steroid therapy is common; however, the spontaneous regression of PCNSL without any treatment is extremely rare. This study presented a rare case of PCNSL with preceding pseudotumoral demyelination and no previous steroid treatment, and the pitfalls of PCNSL diagnosis were discussed. A 70-year-old healthy male experienced memory and gait disturbances and showed multiple enhanced lesions with perifocal brain edema in the left cerebrum. The patient had no previous symptoms, no chronic lesions and negative oligoclonal immunoglobulin G bands in the cerebrospinal fluid. Histological examination of a brain biopsy specimen revealed predominantly destructive, demyelinating characteristics with infiltration of several T lymphocytes and foamy macrophages resulting in the diagnosis of multiple sclerosis. The patient received steroid therapy and demonstrated gradual improvement, multiple brain lesions had disappeared from the magnetic resonance imaging (MRI)scan two months after the biopsy. However, three months after the biopsy, the condition of the patient deteriorated. MRI indicated a homogeneous enhanced lesion in the right frontal lobe and a second biopsy was performed. Histological examination during the second biopsy revealed a diffuse large B-cell lymphoma. The patient received whole-brain radiation and steroid therapy, however, succumbed eight months following the initial diagnosis. In the current report a comparison between the our case and six previously reported cases is presented.

Acquired overt cytomegalovirus infection in immunocompetent adult patients

There has been analyzed the clinical course of the disease in 94 hospitalized patients with acute acquired overt cytomegalovirus infection, confirmed by serological tests and polymerase chain reaction. Males of young age were shown to suffer more often. In the clinical picture symptoms of intoxication (fever, weakness), hepatomegaly with increased activity of liver enzymes, splenomegaly, the involvement of the airways and lymph nodes available for palpation prevail. The clinical feature of the overt form of cytomegalovirus infection is a frequent combination with infection caused by the Epstein-Barr virus. The comprehensive treatment with introduction of antiviral drugs leads to normalization of temperature, removal of organ lesions and improvement of the patients .

Mortality in patients presenting with fever of unknown origin

Background: Few data exist on the contemporary prognosis of patients presenting with fever of unknown origin (FUO).Methods: The data of 436 adult immunocompetent patients presenting with FUO between 2000 and 2010 and followed for at least 6 months were analyzed, with a focus on FUO-related deaths. The following variables were assessed in survivors and non-survivors: age, underlying diagnosis, and, in a nested case-control design, fever periodicity, selected laboratory parameters (including peripheral blood counts, enzymes, and inflammatory markers) and organomegaly.Results: Thirty FUO-related deaths occurred (6·9%). Malignancy accounted for 11% of fevers but for 60% of deaths. Especially non-Hodgkin lymphoma carried a disproportionally high death toll. In the non-malignant categories, fatality rates were below 6%. All patients discharged without diagnosis in spite of ample investigations (n = 164) survived. Besides malignancy, age, continuous (as opposed to episodic) fever, anaemia, leucopenia, LDH levels, and hepatomegaly were associated with mortality.Conclusions: Fatality rates of FUO have continuously declined over the past decades. Malignancy, including lymphoma, remains a cardinal cause of death. Patients with FUO discharged without diagnosis survive.

Primary Oropharyngeal Tuberculosis—A Differential Diagnosis to Malignancy

Tuberculosis is a communicable disease manifesting as pulmonary and extra pulmonary infection. Extra pulmonary tuberculosis involving pharynx is usually secondary to active pulmonary tuberculosis. Primary oropharyngeal tuberculosis is rare and has been reported in association with immunocompromised states like HIV-AIDS and chronic alcoholism. It has very unusual clinical presentation and sometimes mimics malignancy. We report herewith two cases of primary oropharyngeal tuberculosis, clinically mimicking a malignancy, in immunocompetent adult patients. A high index of suspicion is required to diagnose pharyngeal tuberculosis in patients presenting with ulceroproliferative mass in oropharynx. Histopathological findings of characteristic tuberculous granuloma are confirmatory. Anti-tuberculous therapy gives excellent results within two months of commencing the treatment.

Eumycetoma by Madurella mycetomatis with 30 years of evolution: therapeutic challenge

We report a case of eumycetoma by Madurella mycetomatis on the buttocks and thighs in an adult immunocompetent patient, diagnosed after 30 years of clinical development. He was treated over four years with fluconazol and itraconazol associated with five times surgical excisions of subcutaneous nodules. At the eighth year of follow-up, one nodule recurred on the right infragluteal region, which was excised surgically and has remained asymptomatic ever since.

Isolated tuberculous liver abscess in an immunocompetent adult patient: A case report and literature review

Tuberculous liver abscess is a rare disease entity even in endemic areas of Mycobacterium tuberculosis. It is usually accompanied by pulmonary tuberculosis or enteric tuberculosis. Further, an isolated tuberculous liver abscess is extremely rare. The disease is diagnosed by laparotomy or postmortem autopsy in most cases, and some authors adopted a 9-month antituberculosis regimen. We herein report a case of an isolated tuberculous liver abscess that initially manifested as persistent fever and general malaise, which was diagnosed by liver biopsy and treated successfully with a 6-month antituberculosis regimen and percutaneous abscess drainage.