Audrey Therby

Immune reconstitution inflammatory syndrome in HIV-infected patients with disseminated histoplasmosis.

Four HIV-1-infected patients presented with unusual clinical manifestations in the course of disseminated histoplasmosis, including liver abscesses, compressive lymphadenitis, intestinal obstruction, uveitis and arthritis within a median of 45 days after initiation of highly active antiretroviral therapy (HAART). They had a median increase of 106 CD4 cells/μl and granulomas with caseation in three. Partial immune reconstitution induced by HAART during disseminated histoplasmosis either related to the variety capsulatum or duboisii may be associated with immune reconstitution inflammatory syndrome.

Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial.

BACKGROUND Duration of treatment for patients with vertebral osteomyelitis is mainly based on expert recommendation rather than evidence. We aimed to establish whether 6 weeks of antibiotic treatment is non-inferior to 12 weeks in patients with pyogenic vertebral osteomyelitis. METHODS In this open-label, non-inferiority, randomised controlled trial, we enrolled patients aged 18 years or older with microbiologically confirmed pyogenic vertebral osteomyelitis and typical radiological features from 71 medical care centres across France. Patients were randomly assigned to either 6 weeks or 12 weeks of antibiotic treatment (physicians choice in accordance with French guidelines) by a computer-generated randomisation list of permuted blocks, stratified by centre. The primary endpoint was the proportion of patients who were classified as cured at 1 year by a masked independent validation committee, analysed by intention to treat. Non-inferiority would be declared if the proportion of cured patients assigned to 6 weeks of treatment was not less than the proportion of cured patients assigned to 12 weeks of treatment, within statistical variability, by an absolute margin of 10%. This trial is registered with EudraCT, number 2006-000951-18, and Clinical Trials.gov, number NCT00764114. FINDINGS Between Nov 15, 2006, and March 15, 2011, 359 patients were randomly assigned, of whom six in the 6-week group and two in the 12-week group were excluded after randomisation. 176 patients assigned to the 6-week treatment regimen and 175 to the 12-week treatment regimen were analysed by intention to treat. 160 (90·9%) of 176 patients in the 6-week group and 159 (90·9%) of 175 of those in the 12-week group met the criteria for clinical cure. The difference between the groups (0·05%, 95% CI -6·2 to 6·3) showed the non-inferiority of the 6-week regimen when compared with the 12-week regimen. 50 patients in the 6-week group and 51 in the 12-week group had adverse events, the most common being death (14 [8%] in the 6-week group vs 12 [7%] in the 12-week group), antibiotic intolerance (12 [7%] vs 9 [5%]), cardiorespiratory failure (7 [4%] vs 12 [7%]), and neurological complications (7 [4%] vs 3 [2%]). INTERPRETATION 6 weeks of antibiotic treatment is not inferior to 12 weeks of antibiotic treatment with respect to the proportion of patients with pyogenic vertebral osteomyelitis cured at 1 year, which suggests that the standard antibiotic treatment duration for patients with this disease could be reduced to 6 weeks. FUNDING French Ministry of Health.

Successful medical treatment of Candida albicans in mechanical prosthetic valve endocarditis.

Fungal prosthetic valve endocarditis is particularly serious, and is usually a result of nosocomial candidaemia. This report describes a patient with Candida albicans prosthetic valve endocarditis in whom surgery was believed to be contraindicated. After 45 d of amphotericin B, treatment was continued with fluconazole daily with a follow-up of 16 months, with no recurrent or adverse effects.

Cutaneous melioidosis in adolescent returning from Guadeloupe.

To the Editor: Melioidosis is an emerging zoonosis caused by a highly invasive and drug-resistant bacterium, Burkholderia pseudomallei, that is found in soil and is endemic to Southeast Asia and the Pacific region. Few cases occur in other regions (most imported by travelers) (1–5), but sporadic cases have originated from the Caribbean (6–8). Melioidosis can manifest many years after exposure to B. pseudomallei and can cause severe, systemic infection, including multiple abscesses of internal organs and skin. A less severe manifestation, primary cutaneous melioidosis, causes skin lesions and milder clinical illness. We describe an adolescent patient who had a benign, cutaneous form of melioidosis; she had recently returned to France from Guadeloupe, a Caribbean archipelago. A 15-year-old girl without a medical history, except for asthma, was evaluated in September 2010 for muscle weakness, weight loss of 15%, cough, and fever >40°C. During a trip to Guadeloupe 3 weeks before, she had been infected by dengue virus, along with her brother and father, who recovered rapidly. Treatment with amoxicillin and clavulanic acid was started after her return to France, despite the lack of a clear diagnosis, and induced a slight decrease in fever. Clinical examination showed a body mass index <15, multiple small adenopathies (<10 mm), small papulous skin eruptions, and an inflammatory 15-mm–wide tumefaction on the upper arm, evoking an adenopathy on ultrasound investigation. Biological screening 2 weeks later showed persistence of inflammation. Results of serologic tests for cytomegalovirus, Epstein-Barr virus, parvovirus B19, chikungunya virus, Rickettsia, Coxiella, Chlamydia, Brucella, and Borrelia spp. did not show acute infectious disease; results were positive for recent mycoplasma infection, despite absence of typical signs and symptoms. A 2-week treatment regimen with spiramycin was started; general improvement followed, and the cough resolved. The tumefaction of the upper arm persisted, and a biopsy was performed. Histologic results were nonspecific; culture on sheep’s blood Columbia agar and chocolate agar produced small colonies of gram-negative bacilli after 24 hours’ incubation at 35°C in an atmosphere of 5% CO2. This bacillus was later identified as B. pseudomallei by using the Vitek2 test card (bioMerieux, Marcy l’Etoile, France). Identification was confirmed by sequencing of 16S rRNA. The patient was treated with intravenous ceftazidime (150 mg/kg for 10 d), followed by oral cotrimoxazole (800 mg of trimethoprim and 160 mg of sulfamethoxazole, 2×/d), with a total treatment duration of 12 weeks. Eleven weeks after treatment ended, the patient had recovered, and the tumefaction of the arm had disappeared. The differential diagnosis for primary cutaneous melioidosis includes pyogenic abscesses, insect bites, mycobacterial and other granulomatous lesions, and adenopathies, but melioidosis is usually not suspected in these conditions, particularly in patients from non–disease-endemic regions such as the Caribbean. Clinical phenotypes of melioidosis range from asymptomatic carriage to fulminant shock syndrome (1–5); death rates for the latter are ≈100% (3). Subacute melioidosis may be associated with pulmonary and general signs; chronic variants could give rise to abscesses or septicemia in cases of concomitant immunodeficiency (1–5), even decades after exposure. Signs and symptoms of melioidosis can mimic those of tuberculosis, even though there is no link between the infectious agents (2,4). Cutaneous melioidosis may be primary (a single, nonspecific, sometimes ulcerated lesion, measuring from several millimeters to several centimeters) or secondary (multiple lesions associated with visceral infection). In a study of 486 melioidosis patients in Australia, 58 (12%) had the primary cutaneous form (9). These cases were characterized by younger patient age (more common among children <16 years of age), higher frequency during the dry season, better prognosis in spite of a possible chronic evolution, and absence of classic risk factors (9) such as diabetes, alcoholism, chronic renal or pulmonary infections, surgery, pregnancy, or cystic fibrosis (1–5). The case we describe is consistent with the cutaneous variant of melioidosis. However, the patient’s initial general symptoms (probably attenuated by early treatment with antimicrobial drugs) could have indicated a transitory, disseminated phase of disease such as that experienced by 4 (all adults) of the 58 cases of primary cutaneous melioidosis in the Australian study (9). It is not known whether B. pseudomallei was transmitted to the patient by an airborne route or percutaneously as in most cases (i.e., wounds infected by contaminated water or mud); other transmission modes are anecdotal (1–5). Moreover, our patient had none of the classic risk factors, although dengue fever as an underlying co-infection has been described (10). The patient was treated with intravenous ceftazidime and oral cotrimoxazole at the minimum treatment duration recommended for melioidosis (1–5). Purely cutaneous variants of melioidosis may be treated exclusively by oral cotrimoxazole over 12 weeks (9), but we opted to prescribe initial intravenous treatment because of her general symptoms. We stopped follow-up 11 weeks after the treatment period ended because of persisting illness remission, but lifelong monitoring is recommended for adult patients (1,4) because relapses occur in ≈10% of adult patients despite well-conducted antimicrobial drug treatment (3,4). In conclusion, melioidosis as a potential emerging infectious disease should be considered in cases of isolated skin lesions as well as in cases of unexplained fever with nonspecific symptoms. Furthermore, the disease should be considered not only among travelers returning from known disease-endemic regions but also in those coming from the Caribbean.

Prevalence of Mixed Cryoglobulins in Relation to CD4 Cell Count among Patients Coinfected with HIV and Hepatitis C Virus

Cryoglobulinemia was studied in human immunodeficiency virus-positive, hepatitis C virus (HCV)-positive patients in relation to their CD4 cell count. Cryoglobulinemia was found in 18 (31.6%) of 57 patients: 17 (44.7%) of 38 patients with a CD4 cell count of >or=200 cells/ micro L versus 1 (5.3%) of 19 patients with a CD4 cell count of <200 cells/ micro L (P=.0064). Cell-mediated immunity could, therefore, contribute to the production of HCV-associated cryoglobulins.

Efficacy of Imipenem for the Treatment of Bacteremia Due to an OXA-48-Producing Klebsiella pneumoniae Isolate

Correspondence Efficacy of Imipenem for the Treatment of Bacteremia Due to an OXA-48-Producing Klebsiella pneumoniae Isolate To the Editor—Resistance to carba-penems in Enterobacteriaceae is emerging worldwide [1, 2]. The enzymes that are responsible for the resistance are mostly clavulanic acid–inhibited carba-penemase (KPC), metallo-b-lactamases (Verona integron-related metallo-b-lactamase [VIM], IMP-type carbapene-mases, New Delhi metallo-b-lactamase), and b-lactamases of the OXA-48 type [3]. The bacterial strains that produce these enzymes are multidrug-resistant [1, 3]. The efficacy of carbapenems for treating infections due to carbapenemase producers with low-level resistance or susceptibility to several carbapenem molecules remain debatable [4]. We report now a case of successful treatment with imipenem in bacteremia that was due to OXA-48-producing Klebsiella pneumoniae. A 61-year-old female was admitted in December 2010 to the intensive care unit for septic shock syndrome and acute pancreatitis. On day 12, a rectal screening swab was positive for a multidrug-resistant K. pneumoniae isolate. At 24 days after her admission, the patient was febrile (39°C). A blood culture withdrawn from a ca-theter was positive for a K. pneumoniae with the same multidrug-resistant pattern. Ertapenem (1 gram every day) was administered before the results of identification and susceptibility testing. Both isolates were found to be clonally related or identical according to pulse-field gel analysis (data not shown), and of the sequence type 101 [5]. They were resistant to ertapenem (minimum inhibitory concentration [MIC] 4 mg/L) and susceptible to imipenem (MIC 0.38 mg/L) according to results of the Etest techniques following the updated Clinical and Laboratory Standards Institute guidelines [6]. They were resistant to expanded-spectrum cephalosporins (cefotaxime, ceftazidime, and ceftriaxone), fluoroquinolones, cotri-moxazole, kanamycin, gentamicin, and tobramycin. A molecular-based analysis identified a narrow-spectrum b-lactamase TEM-1, a clavulanic-acid inhibited CTX-M-15, and the carbapenemase OXA-48 using described techniques. Ertapenem was then replaced by imi-penem (1 gram every 8 hours) over 12 days. Then, all blood cultures withdrawn during the imipenem treatment tested negative for K. pneumoniae. This report underlines that laboratory detection of OXA-48 producers may be difficult. Indeed, the extended spectrum b-lactamase–producing strain isolated first from the rectal swab had not been detected as OXA-48-producing K. pneumoniae since it was susceptible to imipenem. Additional testing for ertapenem may be helpful for detecting this mechanism of resistance. In addition, this clinical case shows that certain carbapenem molecules could be used to treat infections with En-terobacteriaceae that produce OXA-48-type carbapenemases. In animal infection models, carbapenems are effective against VIM-producing K. pneumoniae with car-bapenem …

Kikuchi-Fujimoto disease associated with mixed connective tissue disease

Kikuchi-Fujimoto disease is characterized by painful cervical lymphadenopathy and constitutional symptoms. Microscopical study of lymph nodes shows focal areas of non-suppurative necrosis with histiocytic and plasmacytoid cell infiltrates. The course is usually benign. Often primitive, necrotising histiocytic lymphadenopathy may be associated with autoimmune disorders. We describe the case of a 30-year-old female patient with two 15-day courses of Kikuchi-Fujimoto disease flares within a period of 3 months, occurring in association with mixed connective tissue disease.

Adult-onset Still's disease revealed by perimyocarditis and a concomitant reactivation of an EBV infection

We describe a 17-year-old patient presenting perimyocarditis as the initial manifestation of the adult-onset Stills disease. Corticotherapy was rapidly successful but induced major acute hepatitis in relation with Epstein-Barr virus reactivation. After 1 year, even if the global outcome is favourable, a slightly lowered ejection fraction still persists. Former case reports and differential diagnosis with reactive haemophagocytic syndrome would be discussed.

Pyogenic vertebral osteomyelitis of the elderly: Characteristics and outcomes

Background The incidence of pyogenic vertebral osteomyelitis (PVO) has increased over the past two decades. One possible cause of this increase is the aging of the population, which results in more comorbidities in high income countries. Objective To better characterize the clinical presentation and outcome of PVO in the elderly. Design We conducted a post-hoc analysis of a previously published trial that studied treatment duration in PVO and compared the presentation and outcomes according to age. Participants Our analysis included 351 patients among whom 85 (24%) were 75-years-old or more. Results There were no significant differences in the socio-demographics of the patients. Neoplasia and chronic inflammatory diseases were more common in the older group: 34% vs. 19% (p = 0.021) and 9% versus 1% (p = 0.004), respectively. There were no significant differences in clinical and radiological presentations between the groups in terms of back pain (337/351, 97%), fever (182/351, 52%), PVO localization, neurological signs and epidural abscess. Associated infective endocarditis (IE) was more frequent in the older group (37% vs. 14%, p<0.001). Streptococci were more frequently involved in infections of older patients (29% vs. 14%, p = 0.003) in contrast to Staphylococcus aureus (31% vs. 45%, p = 0.03). Older patients displayed higher mortality rates at 1 year (21% vs. 3%, p<0.001) and more adverse events related to cardiorespiratory failure (10.6% vs. 3.8%, p = 0.025), but had similar quality of life among the survivors. Conclusion During PVO, the clinical and radiological findings are similar in older patients. Global mortality rates are higher in older patients compared to younger patients, which could be explained by the increased frequency of neoplasia at diagnosis and higher prevalence of associated IE in the elderly.

Concomitant axillary mycobacteriosis and neuro-sarcoidosis: diagnostic pitfalls

There are many similarities between mycobacteriosis, in particular, tuberculosis, and sarcoidosis such as predominant intrathoracic localisation (even if all organs and tissues may be concerned), great variability of phenotypic expression, and granulomatous inflammatory reaction, caseous necrosis not being an absolute criterion of tuberculosis. Moreover, microbial (or mycobacterial?) agents may play a role in the pathogenesis of sarcoidosis which remains a diagnosis of exclusion particularly in atypical cases. The authors report a case of a non-immunocompromised female patient who presented, simultaneously, isolated axillary tubercular adenitis and neuro-sarcoidosis without any other localisation. This case illustrates the difficulty to distinguish between both of these two diseases and thus to choose an adequate treatment when diagnosis is not proven. Moreover, our patient (human leucocyte antigen B27 positive) presented symptoms of spondylarthritis which also may have a nosological link with tuberculosis or sarcoidosis.