Fever of unknown origin revealing testicular nocardiosis: a case report and literature review.

BACKGROUND: Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis. CASE PRESENTATION: We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient's condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis. CONCLUSIONS: To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.

Fever Without an Apparent Source in Young Infants: A Multicenter Retrospective Evaluation of Adherence to the Dutch Guidelines.

BACKGROUND: The Dutch fever without an apparent source (FWS) guidelines were published to timely recognize and treat serious infections. We determined the adherence to the Dutch FWS guidelines and the percentage of serious infections in infants younger than 3 months of age. Second, we identified which clinical criteria, diagnostic tests, and management were associated with nonadherence to the guidelines. METHODS: A retrospective cohort study was performed in 2 Dutch teaching hospitals. We assessed the charts of all infants with FWS who presented at the emergency departments from September 30, 2017, to October 1, 2019. Diagnostic and therapeutic decisions were compared with the recommendations, as published in the Dutch guidelines. Infants were categorized into the nonadherence group in case 1 or more recommendations were not adhered to. RESULTS: Data on 231 infants were studied; 51.5% of the cases adhered to the Dutch guidelines and 16.0% suffered from a serious infection. The percentage of infants with a serious infection was higher in the adherence compared with the nonadherence group. We observed no relevant differences in clinical outcomes. Univariate regression analysis showed that an abnormal white blood cell count was associated with nonadherence (OR 0.4, P = 0.049). Not obtaining a urine and blood culture and not starting intravenous antibiotic treatment were the most frequent reasons for nonadherence to the guidelines. CONCLUSIONS: Our study indicates that there was nonadherence in a large proportion of FWS cases. The guidelines may need to be adjusted to increase adherence.

[Isolation and identification of Leptospira in patients with fever of unknown origin in Guizhou province].

Objective: To understand the etiological characteristics of the patients with fever of unknown origin in Guizhou province through the isolation and identification of Leptospira interrogans and provide evidence for the control, prevention and treatment of human leptospirosis. Methods: Blood and urine samples were collected from patients with fever symptoms in Qiandongnan, an epidemic area, in Guizhou. The suspected Leptospira strains were primarily identified using pathogenic Leptospira specific G1/G2-PCR, and subsequently identified by using Leptospira serogroups specific PCR. The Leptospira strains were then genotyped with multiple locus sequence typing. MLST data based cluster analysis on the isolates and Leptospira reference strains of common serogroups were analyzed by using software NTsys 2.10e. Results: Three suspected strains of Leptospira were isolated from human blood samples, the isolation rate was 8.６%, which were designated as strain 17BX002, 17BX003 and 17AJX008. Strain 17BX002 was further identified as serogroup grippotyphosa by using Leptospira serogroup specific PCR, while the other two strains were negative (excluded as iterohaemorrhagiae, sejroe, canicola, autumnalis, grippotyphosa and hebdomadis). MLST genotyping showed that strain 17BX002 was typed as ST106, most closely clustered with Leptospira grippotyphosa, while strain 17BX003 and 17AJX008 were typed as ST96, the same as serogroup badaviae. Conclusion: There are leptospirosis cases in epidemic area of Guizhou in high incidence season, grippotyphosa and bataviae are the newly discovered serogroups of Leptospira in Guizhou.

Etiologic Agents of Fever of Unknown Origin Among Patients Attending Mnazi Mmoja Hospital, Zanzibar.

BACKGROUND: Fever of unknown origin (FUO) remains an important public health problem. With malaria transmission declining in some parts of Africa, the evidence suggests other infectious agents now account for most FUO. The purpose of this study was to identify the etiologic agents of FUO in a cross-section of patients at the Mnazi Mmoja hospital in Zanzibar, Tanzania. METHODOLOGY: A multiplex TaqMan gene expression Array Card (TAC) and plates were used for detection and classification of different pathogens in blood samples obtained from patients with FUO. Logistic regression analyses was performed using pathogens detected and sociodemographic characteristics as outcome and exposure variables respectively. Odd ratios and 95% confidence interval were calculated and statistical significance was set at P < .05. RESULT: Thirty-three different pathogens were detected in 27 patient blood samples. The following pathogens were detected in decreasing order of prevalence; Dengue virus, Plasmodium species, Rickettsia, Brucella species, Salmonella typhi, and less than 1% for each of Bartonella, Coxiella burnetii, Salmonella species, and Leptospira. Co-infections of Plasmodium with Dengue and S. typhi were also detected, including one case with three different pathogens-Plasmodium, Rickettsia and Brucella. There was no association between the etiologic agents of FUO and demographic or clinical characteristics. CONCLUSIONS: Zoonotic and arboviral etiological agents of fever of unknown origin are present among patients at the Mnazi Mmoja hospital in Zanzibar, Tanzania. There is a need to develop a baseline of standardized diagnostic approaches particularly within the hospital setting. In areas with low malaria prevalence like Zanzibar, Dengue, Rickettsia, Coxiella burnetii, Brucellosis should be considered by clinicians in the differential diagnoses of FUO.

Fever of Unknown Origin in a Renal Transplant Recipient: Lactate Dehydrogenase as an Important Clue to Diagnosis.

Histoplasmosis is a rare disease in nonendemic areas. We report a case of a 23-year-old male patient who presented with fever of unknown origin, cytopenias, organomegaly, and allograft dysfunction 4 months after renal transplant with father as donor. Bone marrow examination showed intracellular budding yeast cells, which was confirmed as histoplasmosis by culture of bone marrow biopsy sample. The patient was treated with intravenous liposomal amphotericin and responded well.

Fever of unknown origin caused by infectious diseases in the era of migrant and refugee crisis.

Concern exists in Europe about the possibility of importation of infectious diseases due to the recent influx of migrants and refugees after 2011. In this retrospective 6-year study, we examined the epidemiology of fever of unknown origin (FUO) in Greece over the past years. Forty-eight patients with classical FUO were included. The proportion of infectious causes of FUO (29.2%) was similar to previous studies in Greece and all infections were endemic to the area. Disease-related mortality was 12.5% and no deaths due to infection were recorded. In conclusion, none of the diagnosed infectious causes of FUO raised concerns about the possibility of imported diseases or pathogens. These results re-inforce the perception that migrants and refugees are not carriers of communicable diseases that can cause public health problems to European countries.

Clinical profile of tuberculosis in patients with chronic kidney disease: A report from an endemic Country.

The objective is to study the clinical profile of tuberculosis (TB) in chronic kidney disease (CKD). This is retrospective study of CKD patients who were diagnosed to have TB over a period of seven years at a tertiary care hospital. TB was diagnosed in 115 patients with an incidence of 4200/100,000. Mean age of the patients was 46.9 ± 16 years. Sixty-two patients (53.9%) were male. Causes of CKD were diabetic nephropathy and hypertension in 11.3% each, chronic glomerulonephritis in 31.3%, chronic tubulointerstitial nephritis in 39.1%, autosomal dominant polycystic kidney disease, and post-renal transplant CKD in 3.5% each. About 68.7% of patients with TB had advanced CKD stage of 4-5D, whereas 31.3% of patients had early CKD stage 1-3. Twenty percent of patients were on dialysis. Three-fourths of the patients had extrapulmonary TB. Pleuropulmonary (41.8%), kidney and urinary tract (20%), and abdomen and lymph node (13% each) were the most common sites for TB. The main clinical presentation of TB was: fever/pyrexia of unknown origin in 24.3%, constitutional symptoms of anorexia, fever, night sweats, and weight loss in 27.8%, abnormal chest radiograph in 31.2%, ascites/peritonitis in 13.9%, pleural effusion in 25.2%, lymphadenopathy in 20%, and sterile pyuria/hematuria/chronic pyelonephritis in 13%. Microbiological and/or histopathological diagnoses were made in 45.2% and in the other 54.8%, diagnosis of TB was made on clinical grounds. Adverse effects of anti-TB drugs were seen in 9.6% of patients. Ninety-three percent completed the treatment and survived. Eight patients (7%), all in CKD stage 5D, died. The incidence of TB was high among CKD stages 4 and 5 and in those receiving dialysis. Extrapulmonary disease such as pleuropulmonary, renal, peritoneal, and lymph node were the common forms of TB.

Combined Laboratory Approach to Detection of Parvovirus B19 and Coxiella Burnetii in Patients with Fever of Unknown Origin.

BACKGROUND: Fever of unknown origin (FUO) is one of the greatest challenges for clinicians and patients. There are more than 200 etiological agents of FUO, among these the most common is the role of infection, neoplasms, and diseases of connective tissue. The aim of the present study is to investigate the role of the infectious agents parvovirus B19 (B19V) and Coxiella burnetii (C. burnetii) in the development of fever of unknown origin by a set of immunoenzymatic and molecular methods. METHODS: The present study included a total of 70 adult patients diagnosed with FUO and hospitalized in Bulgarian Hospitals. A control group of 26 healthy people were also included. Serological (indirect enzyme immunoassay test for detection of B19V and C. burnetii Ph. II specific IgM/IgG) and molecular (extraction and detection of infectious nucleic acids) methods were used. RESULTS: From all patients with FUO, a positive result for B19V-IgM was obtained in 18/70 (25.71%, 95% CI: 15.47 - 35.95) and the highest percentage was found in age groups 0 - 9 and 10 - 19 years. Protective B19V immunity and past viral infection was reported in 41/70 (58.57%, 95% CI: 47.03 - 70.11), and this percentage corresponded with the control group 16/26 (61.54%, 95% CI: 42.84 - 80.24). Anti-C. burnetii Ph. II-IgM was demonstrated in 13/70 (18.57%, 95% CI: 9.46 - 27.68). A relatively high percentage of affected patients were ≤ 40 years. Anti-C. burnetii Ph. II-IgG was detected in 24/70 (34.29%, 95% CI: 23.17 - 45.41). The control group has a 100% negative result for acute B19V and C. burnetii infection. A positive B19V-DNA result was obtained in 12/70 (17.14%, 95% CI: 8.31 - 25.97) patients. In 11/12 (91.67%) it was in combination with positive B19V-IgM marker. Of the total 70 sera tested, a positive PCR results for C. burnetii-DNA were obtained in 11 (15.71%, 95% CI: 7.18 - 24.24). According to clinical manifestation and concomitant symptoms, a high percentage of B19V and C. burnetii positives were associated with FUO and fever, headache, chills, and rash. CONCLUSIONS: It is of particular importance for a correct diagnosis of FUO to use a combined laboratory approach to prove acute or persistent infection and to test for a set of etiological agents.

Detección de parechovirus humanos en muestras respiratorias en menores de 2 meses con fiebre de origen desconocido / Detection of human Parechovirus in respiratory samples in the neonatal population with fever of unknown origin

No disponible

Diagnostic utility of bone marrow examination in evaluation of fever: a descriptive study on 98 immunocompetent adults from a tertiary care institute in south India.

Five-year clinico-laboratory data from 99 (one HIV seropositive) adults (mean age = 41.3 ± 20.4 years) who underwent bone marrow examination for fever persisting for ≥ 1 week were analysed and correlated with microbiological characteristics. Infections, reactive marrow changes and haematolymphoid malignancies were most commonly associated with fever. A high concordance rate of 71% was noted between aspiration and trephine biopsies. Bone marrow granulomas (BMG) were seen exclusively on sections and were most commonly of tubercular and typhoidal in origin (two Salmonella Typhi, one Salmonella Paratyphi A). The common aetiologies associated with fever and cytopenia(s) were BMG, acute leukaemia and haemophagocytic lymphohistiocytosis (HLH; n = 3). The yield from bone marrow culture was inferior compared to other body fluids. In conclusion, bone marrow histology is superior to smears in the evaluation of prolonged fever. Marrow culture may not be useful in immunocompetent individuals other than if Salmonellosis is suspected.

Molecular diagnosis and source tracing of an infection of Aureobasidium pullulans.

Aureobasidium pullulans (A. pullulans) is a dematiaceous, yeast-like fungus that is ubiquitous in nature, which can colonize the human hair and skin. A. pullulans has been clinically implicated to cause skin and soft tissue infections, meningitis, splenic abscesses, and peritonitis. Herein, molecular diagnostic of internal transcribed spacer (ITS) sequencing was used to investigate a suspected case of A. pullulans infection, and the infection source had been traced. A 27-year-old female case was suspected of kala-azar due to the recurrent fever. Bone marrow specimens were analyzed. The samples were negative for Leishmania, Penicillium marneffei and Histoplasma capsulatum. DNA was extracted from the bone marrow specimens, and the 583-bp sequence was amplified with the fungal ITS universal primers. The sequence was compared by Blast query to be identified as A. pullulans. A strain of A. pullulans was also isolated from the kitchen of the patient's living room. Culture characteristics were the same as the human pathogens of A. pullulans, and the ITS sequence was identical to the bone marrow ITS amplification. In conclusion, a deep infection caused by A. pullulans is rare, often occurring in the indwelling catheter, which may cause peritonitis and other symptoms. ITS sequencing of fungi can be used as a diagnostic reference. As A. pullulans is a common fungus in environment, amplification of ITS sequence of A. pullulans in the aseptic body fluid would be necessary to make a comprehensive diagnosis based on the clinical symptoms and signs.

Etiology of Fever of Unknown Origin in Children from Mumbai, India.

This descriptive study evaluated 49 children with fever lasting for more than 7 days at a tertiary hospital in urban Mumbai. Etiologic diagnosis could be established in 88% of the cases. Infections were the causein 34 (79%)patients, 6 (14%) were diagnosed as collagen vascular diseases, and 3 (7%) had other cause.

Lessons learned from splenic infarcts with fever of unknown origin (FUO): culture-negative endocarditis (CNE) or malignancy?

Culture negative endocarditis (CNE) is a common concern in patients with fever, heart murmur, cardiac vegetation, and negative blood cultures. The diagnosis of CNE is not based only on negative blood cultures and a cardiac vegetation. The clinical definition of CNE is based on negative blood cultures plus the findings of culture positive infective endocarditis (IE), e.g., fever, cardiac vegetation, splenomegaly, peripheral manifestations. Because embolic splenic infarcts may occur with culture positive IE, some may assume that splenic infarcts are a sign of CNE. Previously, CNE was due to fastidious and non-culturable organisms. With current diagnostic methods, fastidious organisms grow in 2-3 days. Therefore, fastidious IE are a subset of culture positive IE, but do not represent true CNE. We describe a case of an elderly female who presented with a fever of unknown origin (FUO) and multiple splenic infarcts thought by some to represent CNE. An extensive workup for CNE pathogens was negative. The final cause of her splenic infarcts was a diffuse large B-cell lymphoma (DLBCL). Review of the literature, as well as this case, confirms that splenic infarcts are not a feature of CNE. In patients with fever, splenic infarcts, and negative blood cultures, physicians should search for an alternate explanation rather than CNE, e.g., malignancy and hypercoaguable state (lupus anticoagulant).

Rhinovirus in Febrile Infants and Risk of Bacterial Infection.

BACKGROUND: Febrile infants with viral respiratory infections have a reduced risk of bacterial infection compared with virus-negative infants. The risk of concomitant bacterial infection in febrile infants positive for human rhinovirus (HRV) by polymerase chain reaction (PCR) is unknown. METHODS: Infants 1-90 days old managed using the care process model for well-appearing febrile infants and with respiratory viral testing by PCR (RVPCR) in the emergency department or inpatient setting of 22 hospitals in the Intermountain Healthcare system from 2007-2016 were identified. Relative risk (RR) of bacterial infection was calculated for infants with HRV, non-HRV viruses, or no virus detected. RESULTS: Of 10 964 febrile infants identified, 4037 (37%) had RVPCR. Of these, 2212 (55%) were positive for a respiratory virus; 1392 (35%) for HRV alone. Bacterial infection was identified in 9.5%. Febrile infants with HRV detected were more likely to have bacterial infection than those with non-HRV viruses (7.8% vs 3.7%; P < .001; RR 2.12 [95% CI 1.43-3.15]). Risk of urinary tract infection was not significantly different for HRV-positive infants at any age, nor was risk of invasive bacterial infection (IBI; bacteremia and/or meningitis) meaningfully different for infants 1-28 day olds. Infants 29-90 days old with HRV had a decreased likelihood of IBI (RR 0.52 [95% CI 0.34-0.80]). CONCLUSIONS: HRV is common in febrile infants. Detection did not alter risk of concomitant urinary tract infection at any age or risk of IBI in infants 1-28 days old. HRV detection may be relevant in considering risk of IBI for infants 29-90 days of age.

Recurrent FUO due to intermittent Enterobacter cloacae bacteremias from an infected pacemaker lead diagnosed by gallium scan.

Fever of unknown origin (FUO) refers to fevers of ≥101° F that persist for ≥3 weeks and remain undiagnosed after a focused inpatient or outpatient workup. FUO may be due to infectious, malignant/neoplastic, rheumatic/inflammatory, or miscellaneous disorders. Recurrent FUOs are due to the same causes of classical FUOs. Recurrent FUOs may have continuous or intermittent fevers and are particularly difficult to diagnose. With intermittent fever, recurrent FUO diagnostic tests are best obtained during fever episodes. With recurrent FUOs, the periodicity of febrile episodes is unpredictable. We present a case of a 70-year-old male who presented with recurrent FUO. Multiple extensive FUO workups failed to determine the source of his fever. During his last two episodes of fever/chills, blood cultures were positive for Enterobacter cloacae. Episodic E. cloacae bacteremias suggested a device-related infection, and the patient had a penile implant and permanent pacemaker (PPM). Following febrile episodes, he was treated with multiple courses of appropriate antibiotics, but subsequently fever/chills recurred. Since a device-associated infection was suspected, indium and PET scans were done, but were negative. The source of his intermittent E. cloacae bacteremias was finally demonstrated by gallium scan showing enhanced uptake on a cardiac lead, but not the penile implant or PPM. Gallium scanning remains useful in workup of FUOs, particularly when false-negative indium or PET scans are suspected. The involved pacemaker lead was explanted, grew E. cloacae and the patient has since remained fever free.