Major causes of fever of unknown origin at Peking Union Medical College Hospital in the past 26 years.

BACKGROUND: Despite the recent advances in medicine, fever of unknown origin (FUO) remains a diagnostic and therapeutic challenge even to expert physicians. To increase the knowledge of FUO, we conducted a retrospective study to investigate the causes of FUO and the change of major causes of FUO during the past 26 years. METHODS: The clinical data were retrospectively analyzed from 997 patients with FUO hospitalized at the Peking Union Medical College Hospital (PUMCH) between January 2004 and October 2010. Furthermore, the results were compared to that reported in previous studies of FUO in PUMCH since 1985. RESULTS: Of the 997 FUO cases, definite diagnosis was eventually achieved in 797 (79.9%) patients. The most common cause of FUO was infectious diseases (479 cases, 48.0%), with tuberculosis accounting for 45.3% (217/479) of the cases of infections. One hundred and sixty-eight (16.9%) patients were diagnosed with connective tissue diseases, with Still's disease and vasculitis accounted for 31.5% (53/168) and 24.4% (41/168) of this category, respectively. Neoplasms and miscellaneous causes were found in 7.9% (79/997) and 7.1% (71/997), respectively. However, no definite diagnosis had been made in the remaining 200 (20.1%) cases until they were discharged from the hospital. CONCLUSIONS: During different periods, infectious diseases, especially tuberculosis, were the leading etiology of FUO and the proportion of tuberculosis had no significant difference. While the frequency of neoplasms was descending, the proportion of lymphoma in neoplasm was ascending; the frequency of undiagnosed cases was increasing, but in most FUO cases the causes can be diagnosed eventually after careful analysis of clinical data.

[A clinical analysis of 25 cases of prosthetic valve endocarditis].

OBJECTIVE: To report the clinical characteristics of prosthetic valve endocarditis (PVE). METHODS: All 25 cases of definite PVE (Duke criteria) diagnosed at our hospital between January 1992 to December 2008 were retrospectively analyzed. Among them, 7 cases were pathologically confirmed and the others were clinically confirmed with either 2 major criteria or 1 major and ≥ 3 minor criteria. Their clinical characteristics, underlying heart diseases, previous heart operations, presenting manifestations, causative microbes, echocardiographic findings and prognosis, were studied. RESULTS: (1) Although most cases underwent valve transplantations for underlying heart diseases of rheumatic heart diseases and congenital heart diseases, 10 patients were complicated with infectious endocarditis (IE) prior to the operations, 4 of them were PVE. (2) Eleven of them developed PVE within 2 months postoperatively. Fever (100%), major vessel embolism (48%), and anemia (36%) were the most frequently manifestations. Fourteen cases (56%) had positive culture results with 15 causative pathogens, including 5 coagulase-negative Staphylococcus (CNS, 3 were methicillin-resistant coagulase-negative Staphylococcus, MRSCoN), 4 fungi, 2 Enterococcus faecalis, 2 Burkholderia cepacia, 1 Stenotrophomonas maltophilia, and 1 Streptococcus. (3) Prosthetic valve vegetations, periannular leakage, regurgitation, were the main echocardiographic findings. Transesophageal echocardiography (TEE) revealed 13 PVE who had no positive findings on previous transthoracic echocardiography (TTE). (4) Eighteen PVE (72%) developed peri-annular complications (12 leakage, 3 dehiscence, 2 abscesses, 1 fistula), major vessel embolism, congestive heart failure (16%) were frequently observed, 9 of the 17 patients died in hospital, in spite of intensive managements. CONCLUSIONS: PVE has a high mortality and is a severe complication for patients who underwent heart surgery. Its causative pathogen spectrum is quite different from that of native valve endocarditis. TTE is not sensitive for some PVE cases.

[An analysis of 100 cases of tuberculosis first presenting as fever of unknown origin in a general tertiary hospital].

OBJECTIVE: To investigate the clinical characteristics of tuberculosis (TB) first presenting as fever of unknown origin (FUO). METHODS: The clinical data of 100 cases of FUO, diagnosed as TB finally, among in-patients in Peking Union Medical College Hospital were analyzed retrospectively. RESULTS: (1) Sites of TB:there were 39 patients with merely pulmonary TB, 28 patients with merely extrapulmonary TB, and 33 patients with both pulmonary and extrapulmonary TB. (2) CLINICAL MANIFESTATIONS: depending on the different sites of tuberculous lesion, the clinical symptoms varied accordingly. The common laboratory findings included anemia, hypoalbuminemia, elevation of the level of ESR and C-reactive protein (CRP). (3) Methods for diagnosis: 34 cases were diagnosed by sputum smear- or cultivation-positive for acid-fast bacilli; 8 cases by histopathology; 49 cases by clinical diagnosis of TB with an effective anti-TB therapy; and 9 cases by effective diagnostic anti-TB therapy. (4) Responses to treatment: among 73 cases with complete follow-up data, only 2 cases (2.7%) died and the other cases were cured or alleviated. Fifty-five cases (77.5%) showed marked efficacy after less than 4 weeks of regular anti-TB therapy, 37 cases (52.1%) suffered adverse effects of anti-TB agents, and all of them had improved after modifying anti-TB therapy and supporting treatment. CONCLUSIONS: The diagnosis of TB that presents as FUO is quite difficult, and the median interval time for making diagnosis is 14 weeks (3 - 77 weeks). Investigating clinical manifestations comprehensively, reviewing radiology data carefully, and eliciting microbiological and pathologic evidence of TB, are extremely important for making the correct diagnosis. In some cases, a therapeutic trial of anti-TB therapy is necessary.

Linezolid for the treatment of infections caused by Gram-positive pathogens in China.

In this randomised, double-blind, comparator-controlled, multicentre study conducted in China, 142 hospitalised patients aged 18-75 years with pneumonia (n=80) or complicated skin and soft-tissue infection (cSSTI) (n=62) due to suspected or known Gram-positive pathogens were randomised (1:1) to receive either linezolid 600mg (n=71) or vancomycin 1g in patients aged < or =60 years or 0.75g in patients aged >60 years (n=71) intravenously every 12h. The duration of treatment was 10-21 days for patients with pneumonia and 7-21 days for patients with cSSTI. Clinical outcomes were assessed at end-of-treatment (EOT) visit and follow-up (FU) visit 7-28 days post therapy. Staphylococcus aureus was the most common pathogen at baseline and most of these isolates were resistant to meticillin. All isolates were susceptible to linezolid and vancomycin. For the evaluable patients, the effective treatment rate for linezolid was higher than that for vancomycin at EOT (86.9% (53/61) vs. 61.7% (37/60)) and at FU (83.1% (49/59) vs. 64.9% (37/57)). Pathogen eradication rates for the microbiologically evaluable patients at FU were 79.2% (42/53) for linezolid and 61.5% (32/52) for vancomycin. The incidence of drug-related adverse events (AEs) was 25.4% (18/71) for linezolid and 16.9% (12/71) for vancomycin. Four (5.6%) linezolid-treated and eight (11.3%) vancomycin-treated patients discontinued the study drug because of an AE. Linezolid was well tolerated and effective for the treatment of infections caused by Gram-positive pathogens, including meticillin-resistant S. aureus.

[Tuberculous meningitis in Chinese adults: a report of 100 cases].

OBJECTIVE: To investigate the clinical features, cerebrospinal fluid (CSF) changes, imaging characteristics, diagnostic methods, treatment regimens and outcomes of Chinese adult patients with tuberculous meningitis (TBM). METHODS: Clinical data of 100 cases of TBM admitted to Peking Union Medical College Hospital from January 1982 to December 2003 were investigated retrospectively. Data were collected with regard to the clinical, laboratory and demographic characteristics of the patients as well as the results of radiological investigations and data of clinical outcome. RESULTS: One hundred TBM cases were included in this study; there were 49 males and 51 females. The mean age was (31 +/- 11) years. Seventy percent of the patients was of chronic duration (11.1 +/- 9.2) weeks. Thirteen cases were definitely diagnosed through positive CSF culture and smear or brain biopsy, the remaining 87 cases were diagnosed clinically. Fever (97%), headache (92%), decreased level of consciousness (71%), meningeal irritation (77%) and impairment of cranial nerve function were the most frequent symptoms and signs. Thirty-five cases were accompanied with active pulmonary tuberculosis and 12 cases with extrapulmonary tuberculosis. Raised intracranial pressure was present in 86%. CSF was non-purulent with lymphocytic pleocytosis, marked elevation of protein concentration and significant decrease of glucose. Sixty-seven cases had imaging data; abnormalities were found in 52 with ventricular enlargement, hydrocephalus and infarction the most frequent findings. All the patients received anti-tuberculosis therapy, nine underwent neurosurgical drain due to hydrocephalus, eighty-one improved and seven died. CONCLUSIONS: TBM should be suspected when chronic meningitis was accompanied with active pulmonary or extrapulmonary tuberculosis. Differential diagnosis and trial anti-tuberculosis therapy may be of help for the diagnosis. Positive CSF smear and culture and biopsy of brain or meninges are the golden standards for the diagnosis of TBM. Early diagnosis and treatment are very important for improving the outcome.

[Clinical characteristics of 143 Chinese HIV/AIDS patients].

OBJECTIVE: To investigate the clinical characteristics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients in China. METHODS: Totally 143 HIV/AIDS patients who were first diagnosed in Peking Union Medical College Hospital form January 1988 to April 2006 were enrolled in this study. Clinical characteristics were retrospectively analyzed. RESULTS: Among 143 HIV/ AIDS patients, 57 patients had no clinical symptoms and were confirmed by routine examinations; 86 patients had clinical symptoms, including fever (n = 50), weight loss (n = 18), and discomforts involving respiratory system (n = 34), gastrointestinal system (n = 16), and derma and mucosa (n = 17). Opportunistic infections (OIs) such as pneumocystis jiroveci pneumonia (PCP) (n = 27), oropharyngeal candidiasis (n = 16), tuberculosis (n = 15) , and cytomegalovirus (CMV) infection (n = 9) were also observed in patients whose CD4 + T cell counts were less than 200/mm3. Most CMV infection and cryptococcal meningitis occurred in patients whose CD4 + T cell counts were less than 100/mm3. CD4 + T cell count was negatively correlated with plasma viral load (r = -0.420, P = 0.001). CONCLUSIONS: Fever, dyspnea, and weight loss are the most common symptoms in the patients of this study. The respiratory system, gastrointestinal system, derma and mucosa are the most commonly affected areas by OIs, and PCP is the most common OI. The occurrence of OIs corelates with CD4 + T cell count.

[A clinical analysis of 22 cases of Pneumocystis pneumonia in acquired immunodeficiency syndrome].

OBJECTIVE: To investigate the clinical characteristics, therapeutical approaches and outcome of Pneumocystis pneumonia (PCP) in patients with AIDS. METHODS: The clinical data of 22 PCP patients with AIDS who were treated in Peking Union Medical College Hospital from January 1992 to October 2004 were analyzed, including the routes of HIV infection, clinical profiles, immunological status, chest radiological characteristics, therapeutic managements and outcome. RESULTS: (1) Of the 22 PCP patients, 16 were male and 6 female. The average age was (35.0 +/- 9.4) years old. The majority of patients got HIV infection through blood transfusion (54.5%) and sexual transmission (27.3%). (2) The common clinical presentations were fever (21/22), progressive exertional dyspnea (20/22), cough (16/22), sputum (12/22) and weight loss (18/22). 68.2% (15/22) of the patients had normal or mild coarse breath sounds on auscultation. 14 patients had an PaO(2) less than 60 mm Hg (1 mm Hg = 0.133 kPa). (3) All the 22 PCP cases were in their late stage of AIDS. For the 20 patients who had an immunological test, the peripheral CD(4)(+) T lymphocyte count was ranging from 3 x 10(6)/L to 148 x 10(6)/L and 90% of the cases had a CD(4)(+) T cell count less than 100 x 10(6)/L, 95% of the cases had a CD(4)(+)/CD(8)(+) ratio less than 0.20; (4) The most common abnormal chest radiological findings were bilateral diffuse interstitial infiltrations (19/22) and patchy shadows (14/22); (5) All patients were given trimethoprim-sulfamethoxazole (SMZco) and 86.4% of the patients were treated with corticosteroids concomitantly. Of the 22 PCP patients, 13 recovered, 5 gave up after knowing their definite diagnosis, 4 died. Comparing with the recovery patients, the 4 patients who died of PCP had much lesser CD(4)(+) T cell count (P = 0.07). CONCLUSIONS: Most PCP occurred in patients who were in their late stage of AIDS and with a CD(4)(+) T cell count below 100 x 10(6)/L. For these reasons, we suggest that whenever encountering a young patient presenting with fever, dyspnea, hypoxia, loss of weight, the possibility of PCP complicating AIDS should be considered, especially when chest radiological study revealed interstitial infiltration or patchy shadows. If HIV was confirmed to be positive, the combined therapy of SMZco and corticosteroids should be started immediately.

[A clinical analysis of 57 cases of abdominal tuberculosis].

OBJECTIVE: To explore the clinical characteristics and diagnosis methods of abdominal tuberculosis. METHODS: The clinical characteristics of abdominal tuberculosis in 57 cases proved by histopathology between 1958-2004 were retrospectively analyzed. RESULTS: There were 39 cases of tuberculosis of the liver, 5 cases of the spleen, 8 cases of the pancreas, 3 cases of the stomach, 1 case involved both liver and spleen and 1 case involved both liver and stomach. Twenty-six patients were males and 31 female; with ages ranged from 17 to 68 years (mean 40.7 years) and most cases (71.9%) having extra-abdominal tuberculosis. Fever (75.4%), fatigue, anorexia, night sweating, weight loss (82.5%) and hepatosplenomegaly (57.9%) were the major clinical manifestations. Elevated erythrocyte sedimentation rate (ESR) (59.6%) and abdominal mass (64.9%) were found in most of the patients. CONCLUSIONS: The diagnosis of abdominal tuberculosis should be considered in all patients with fever of unknown origin, especially in those associated with hepatosplenomegaly, increased ESR and abdominal mass. Aspiration biopsy and laparotomy can provide correct diagnosis. The disease can be effectively treated with surgical intervention and antituberculous chemotherapy.

[A clinical review of 449 cases with fever of unknown origin].

OBJECTIVE: To investigate the causes of fever of unknown origin (FUO). METHODS: The clinical data were retrospectively analyzed from patients with FUO hospitalized in Peking Union Medical College Hospital from January 2000 to December 2003. During that period of time, 449 cases fulfilled the criteria of FUO. RESULTS: Out of the 449 FUO cases, definite diagnosis was eventually achieved in 387 patients (86.9%). The most common causes of FUO were infectious diseases (56.8%), with tuberculosis accounting for 43.6% of cases of infection. Seventy-six patients were suffered from collagen vascular diseases (CVD): with Still's disease, systemic lupus erythematosus and vasculitis accounting for 34.2% (26/76), 18.4% (14/76) and 13.2% (10/76) of the this category, respectively. 16.5% (64/449) of the FUO cases were diagnosed as malignancy. Miscellaneous causes were found in 7.0% of the FUO cases. However, no definite diagnosis had been made in the remaining 62 (13.8%) cases until they discharged from the hospital. CONCLUSIONS: In most FUO cases the causes can be diagnosed eventually after careful analysis of clinical data. While infectious diseases, especially tuberculosis, were still the most common causes of FUO, CVD and malignancy were also major causes of FUO and the incidence of malignancy were increased with the time.

[Clinical analysis of 50 cases of cytomegalovirus disease].

OBJECTIVES: To investigate the clinical features, diagnostic methods, therapeutic approaches, outcomes and the alterations of peripheral lymphocyte subsets in cytomegalovirus (CMV) diseases. METHODS: From August 2000 to October 2002, 50 cases of CMV diseases were treated in Peking Union Medical College Hospital. The diagnosis were made by their symptoms and positive CMV pp65 antigen or/and CMV specific IgM. Of the 50 patients, 15 were male, and 35 female. Their age was (35.5 +/- 16.2) years. Their clinical data were collected, and their peripheral lymphocyte subsets were measured at the time when they were first diagnosed as CMV disease. The lymphocyte subsets of 51 healthy blood donors were tested as normal controls. The lymphocyte subsets were compared between those who had an immunocompromising underlying disease and those who had not. RESULTS: (1) CMV disease occurred in 39 patients who had immunocompromising underlying diseases, and in 11 patients who had not; (2) CMV disease caused various symptoms, most of them were nonspecific. Fever (100%), hematological abnormalities (96%) and abnormal liver function test (30%) were the most common manifestations. 3 cases of CMV retinitis were acquired immune deficiency syndrome patients with CD4+ T cell count less than 50/ microl; 2 patients developed multiple organ failure; (3) The positive rates of CMV pp65 antigen and specific IgM assays were 85.3% and 68.3%, respectively; (4) Comparing with normal controls, all patients with CMV disease had decreased B cell and nature killer cells, increased CD8+ T cell percentage and a reversed CD4+/CD8+ ratio; further more, the patients with underlying diseases had lower CD4+ T-cell and CD8+ T-cell counts than those without underlying diseases. CONCLUSIONS: CMV disease occurred in patients with or without underlying diseases. Their clinical manifestations were heterogeneous and non-specific, therefore, special laboratory tests were necessary to confirm the diagnosis. pp65 antigen assay had more diagnostic value than IgM assay. The dramatic changes in lymphocyte subsets suggest CMV disease has a immunological pathogenesis.

[A clinical analysis of 70 cases of infective endocarditis].

OBJECTIVE: To investigate the clinical characteristics, therapeutical approaches and outcome of infective endocarditis (IE). METHODS: The clinical features, diagnosis, treatment and outcome of 70 IE patients who were treated in Peking Union Medical College Hospital from January 1988 to May 2000 were analyzed. RESULTS: Of the 70 consecutive cases who were diagnosed as IE according to the Duke's new criteria. 38 patients were male and 32 patients female. The average age was (36.1 +/- 16.6) years old. 8 cases were prosthetic valve endocarditis (PVE) and 62 cases native valve endocarditis (NVE). 57 of the 62 (91.9%) NVE patients had pre-existing cardiac abnormalities predisposing to IE, such as congenital cardiovascular disease (22 cases), idiopathic mitral valve prolapse (18 cases), rheumatic heart disease (12 cases), senile degenerative heart disease (3 cases), and permanent pacemaker (PM) implantation 2 cases. Fever (100%), anemia (57.1%) and embolism (47.1%) were the three most common clinical manifestations. Of the 42 cases who had a positive blood culture result, Streptococcus vividans (54.8%) was the most common isolated microorganism. 39 out of the 51 cases receiving antimicrobial therapy and 17 of the 19 cases being treated with combination of antibiotics and surgery were cured. 14 cases including 5 PVE and 2 IE after PM implantation died with a mortality rate of 20%. Intractable congestive heart failure was the leading cause of death. CONCLUSIONS: Congenital cardiovascular diseases and idiopathic mitral valve prolapse were the two most commonly found underlying heart diseases. Blood culture and echocardiogram should always be done to evaluate the possibility of IE while a patient presents with fever of unknown origin, especially when he or she has anemia or embolism. PVE, IE after PM implantation and intractable congestive heart failure were associated with a poor prognosis.

[The adverse reactions of parenteral norvancomycin in 1031 patients].

OBJECTIVE: To investigate the safety of norvancomycin, and provide basis for its rational use in clinical practice. METHODS: We documented all adverse events occurred in inpatients who receive intravenous infusion of norvancomycin, then we evaluated the relationship between adverse events and norvancomycin and calculated the rates of adverse reaction. RESULTS: 1031 patients were enrolled in this study from March 2002 to June 2003 and 965 of them could be evaluated. 80 adverse reactions occurred in 965 patients who received norvancomycin, giving a total adverse reaction rate of 8.29%. The systemic adverse reactions included renal impairment (4.04%), hepatic impairment (2.38%) and allergic reaction (1.76%). 15 patients discontinued the treatment because of the adverse reaction. The rates were higher in patients who use other antimicrobial agents concomitantly or whose age >/= 60 years. The rates of renal impairment were higher in those with age >/= 60 years, and the rates of hepatic impairment were higher in whose received this agent longer than 14 days. These factors were independent risk factors (P < 0.05). CONCLUSIONS: The overall adverse reaction rate of norvancomycin was low. A few patients experienced drug-related reaction, most of these adverse reactions were mild and tolerable. The adverse reactions tended to occur in older patients, those who use other antibiotic concomitantly or those who receive this agent longer than 14 days.

[Nosocomial fungal infections, analysis of 149 cases].

OBJECTIVE: To investigate the manifestation, diagnosis, antifungal therapy and outcome of nosocomial fungal infections. METHODS: The clinical data of 149 patients with nosocomial fungal infections admitted in the PUMC hospital from Dec. 1981 to Nov. 2001, 67 males and 82 females with an average age of 52.32 years, including the manifestation, diagnosis, treatment and outcome, were reviewed retrospectively. RESULTS: 134 out of the 149 patients suffered from deep mycoses. All cases had underlying conditions, including primary pulmonary diseases (n = 29), rheumatic disease (n = 20), hematological disease such as leukemia or lymphoma (n = 18), HIV infection/AIDS (n = 13), major surgery (n = 10), and intracerebral hemorrhage or cerebral infarction (n = 24). The predisposing factors or risk factors for deep mycoses included use of high dose broad-spectrum antibiotics over a long period (n = 37), steroids/cytotoxic chemotherapy (n = 29), immunosuppressant (n = 17), chemotherapy (n = 10), intravenous lines and incubation (n = 36), and tracheotomy or endotracheal intubation (n = 12). The infectious sites were lung, meninges, cerebral parenchyma, blood, etc. in the order of prevalence. Depending on infectious site and type of fungus, the clinical manifestations included fever (63.76%), respiratory symptom such as cough (37.58%), leucocytosis (39.6%), chest X-ray images (24.49%) etc. CNS fungal infection included meningitis, brain abscess, and granuloma. Meningitis due to Cryptococcus resembled that due to Mycobacterium tuberculosis. The main pathogenic fungal species were Candida albicans, C. tropicalis, C. parapsilosis, C. neoformans, and Aspergillus species. Amphotericin B, fluconazole, and flucytosine were used alone or in combination. The overall mortality rate was 29.53% (44/149). Out of the 149 patients 67 were cured, 29 made improvement. The incidence of fungal infection remarkably increased recently with 75 cases appearing in the past 5 years (50.34%). CONCLUSION: The incidence of fungal infection is increasing recently which is correlated with use of high dose broad-spectrum antibiotics over a long period, high dose steroids/cytotoxic chemotherapy, immunosuppressant, chemotherapy, and improvement of examination skills, etc. The main pathogens are still Candida albicans and non-albicans Candida species. Early diagnosis is very important.

[Recombinant virus assay: a rapid assay for assessment of drug susceptibility of human immunodeficiency virus type 1 isolates].

OBJECTIVE: To establish a rapid assay for assessment of drug susceptibility of human immunodeficiency virus type 1 isolates (Recombinant virus assay). METHODS: This procedure allows the generation of viable virus with SI phenotype by homologous recombination of a RT-PCR-derived pool of reverse transcriptase (RT) coding sequences into an RT-deleted, noninfectious proviral clone, pHIV delta RTBstE II. Then the drug susceptibility of recombinant virus to RT inhibitors can be assessed in the Hela CD4+ plaque reduction assays. RESULTS: Analysis of 7 HIV strains with SI or NSI phenotype showed that recombinant viruses accurately exhibited the same genotype as that of the original HIV1 isolates. The results of drug susceptibilities of HIV1 isolate got by recombinant virus assay were the same as that by standardized peripheral blood mononuclear cell culture assay. CONCLUSION: Recombinant virus assay is a rapid and accurate method to assess the drug sensitivity of HIV1 isolates with SI or NSI phenotype.