Background. Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a ...broad spectrum of Candida species. Methods. A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10. Results. Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio OR, 5.8; 95% confidence interval CI, 2.41–13.79; P < .001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21–13.39; P < .001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64–18.94; P < .001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04–0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4–3.8; P = .001). Mycograb was well tolerated. Conclusions. Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.
To examine the effect of inappropriate initial antimicrobial therapy on the prognosis of patients with sepsis who were enrolled in a clinical trial of an immunomodulating agent conducted in 108 ...hospitals in North America and Europe.
We assessed initial antimicrobial choice and results of microbiologic cultures in 904 patients who had microbiologically confirmed severe sepsis or early septic shock. If a patient did not receive at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 hours from the diagnosis of severe sepsis, then the initial antimicrobial treatment was considered to be inappropriate. A propensity score that adjusted for factors associated with inappropriate antimicrobial treatment was calculated and included in multivariable models to adjust for confounding.
A total of 468 patients (52%) had documented bloodstream infection, and 211 patients (23%) received inappropriate initial antimicrobial therapy. Characteristics associated with inappropriate treatment were study enrollment in Europe, admission to surgery, nosocomial infection, infection with multiresistant microorganisms, and fungal or polymicrobial infection (all
P <0.05). The 28-day mortality was 24% (168/693) for patients in the adequately treated group versus 39% (82/211) for patients receiving inappropriate initial antimicrobial therapy (
P <0.001). After adjusting for comorbid conditions, severity of illness, site of infection, and the propensity score, inappropriate antimicrobial therapy was independently associated with increased mortality (odds ratio = 1.8; 95% confidence interval: 1.2 to 2.6).
In a large cohort of patients with microbiologically confirmed severe sepsis, appropriate initial antimicrobial therapy was an important determinant of survival. New approaches aimed at improving detection and treatment of early sepsis are needed.
Candida species are among the most common bloodstream pathogens in the United States, where the emergence of azole-resistant Candida glabrata and Candida krusei are major concerns. Recent ...comprehensive longitudinal data from Europe are lacking. We conducted a nationwide survey of candidemia during 1991-2000 in 17 university and university-affiliated hospitals representing 79% of all tertiary care hospital beds in Switzerland. The number of transplantations and bloodstream infections increased significantly (P < .001). A total of 1137 episodes of candidemia were observed: Candida species ranked seventh among etiologic agents (2.9% of all bloodstream isolates). The incidence of candidemia was stable over a 10-year period. C. albicans remained the predominant Candida species recovered (66%), followed by C. glabrata (15%). Candida tropicalis emerged (9%), the incidence of Candida parapsilosis decreased (1%), and recovery of C. krusei remained rare (2%). Fluconazole consumption increased significantly (P < .001). Despite increasing high-risk activities, the incidence of candidemia remained unchanged, and no shift to resistant species occurred.
Lung transplant recipients are particularly at risk of complications from rhinovirus, the most frequent respiratory virus circulating in the community.
To determine whether lung transplant recipients ...can be chronically infected by rhinovirus and the potential clinical impact.
We first identified an index case, in which rhinovirus was isolated repeatedly, and conducted detailed molecular analysis to determine whether this was related to a unique strain or to re-infection episodes. Transbronchial biopsies were used to assess the presence of rhinovirus in the lung parenchyma. The incidence of chronic rhinoviral infections and potential clinical impact was assessed prospectively in a cohort of 68 lung transplant recipients during 19 mo by screening of bronchoalveolar lavages.
We describe 3 lung transplant recipients with graft dysfunctions in whom rhinovirus was identified by reverse transcriptase-polymerase chain reaction in upper and lower respiratory specimens over a 12-mo period. In two cases, rhinovirus was repeatedly isolated in culture. The persistence of a unique strain in each case was confirmed by sequence analysis of the 5'NCR and VP1 gene. In the index case, rhinovirus was detected in the lower respiratory parenchyma. In the cohort of lung transplant recipients, rhinoviral infections were documented in bronchoalveolar lavage specimens of 10 recipients, and 2 presented with a persistent infection.
Rhinoviral infection can be persistent in lung transplant recipients with graft dysfunction, and the virus can be detected in the lung parenchyma. Given the potential clinical impact, chronic rhinoviral infection needs to be considered in lung transplant recipients.
Background. In addition to the human coronaviruses (HCoVs) OC43 and 229E, which have been known for decades to cause infection in humans, 2 new members of this genus have recently been identified: ...HCoVs NL63 and HKU1. Their impact as a cause of respiratory tract disease in adults at risk for complications needs to be established. Methods. We prospectively assessed the clinical impact of coronavirus infection (excluding cases of severe acute respiratory syndrome) among hospitalized adults. All patients with respiratory disease for whom bronchoalveolar lavage was performed were screened by reverse-transcriptase polymerase chain reaction for the presence of all 4 HCoVs. Results. HCoV was identified in 29 (5.4%) of 540 bronchoalveolar lavage fluid specimens from 279 subjects (mean age, 51 years; 63% male). HCoV OC43 was identified most frequently (12 isolates), followed by 229E (7 isolates), NL63 (6 isolates), and HKU1 (4 isolates). In all, 372 (69%) of 540 bronchoalveolar lavage fluid specimens were negative for bacteria, and 2 persons were coinfected with other respiratory viruses. Transplantation was the most common underlying condition. Of the 29 patients who had HCoV identified in their bronchoalveolar lavage fluid specimens, 9 (31%) were hospitalized in the intensive care unit, 22 (76%) presented to the hospital with acute respiratory symptoms, 16 (55%) presented with cough and/or sputum, 13 (45%) presented with dyspnea, 16 (55%) had experienced prior respiratory infection, and 18 (62%) had a new infiltrate that was visible on chest radiograph. The most frequent final diagnosis was a lower respiratory tract infection. Conclusions. The recently discovered HCoVs NL63 and HKU1 contribute significantly to the overall spectrum of coronavirus infection. Our study also suggests that coronaviruses contribute to respiratory symptoms in most cases.
After a tsunami hit Asia in December 2004, 2 survivors had severe infections due to multidrug-resistant and atypical bacteria and rare fungi weeks afterwards. Treating these infections is challenging ...from a clinical and microbiologic point of view.
Acute respiratory viral infections are generally self-limited in healthy subjects but can lead to severe complications in immunocompromised hosts. We report the clinical impact of acute lower ...respiratory tract viral infections in hospitalized patients.
Of 1,001 fiberoptic bronchoscopies performed during a period of 5 years, 33 BAL samples were positive for respiratory viruses by cell culture. The main diagnosis, length of hospitalization, response to initial treatment, and the mortality rate at 30 days were analyzed. Spirometry performed before and after infection was compared in lung transplant recipients.
The following respiratory viruses were identified in 33 cases: influenza A or B (n = 13), parainfluenza virus 1–3 (n = 7), rhinovirus (n = 5), respiratory syncytial virus (n = 4), and adenovirus (n = 4). All cases were immunocompromised patients who acquired new respiratory symptoms and/or radiologic abnormalities suggesting a pulmonary infection. Twenty-five patients (74%) did not respond to initial broad-spectrum antibiotics, and 11 patients (33%) required intensive care for respiratory failure. The overall mortality rate at 1 month was 24%. In patients with a sole viral pathogen identified in their BAL, the mortality rate was 39%. In lung transplant recipients (n = 10), the mean FEV1 decreased from 2.2 to 1.9 L/s before and during the infection episode, respectively (p < 0.01); 3 months later, 60% of the patients had still not completely recovered to baseline values.
Respiratory viruses recovered in BAL samples of immunocompromised patients are associated with severe lower respiratory complications. In lung transplant recipients, we observed a persisting impairment of pulmonary function.
A substantial proportion of patients become colonised with Candida spp during hospital stay, but only few subsequently develop severe infection. Clinical signs of severe infection manifest early but ...lack specificity until late in the course of the disease, thus representing a particular challenge for diagnosis. Mostly nosocomial, invasive candidaiasis occurs in only 1–8% of patients admitted to hospitals, but in around 10% of patients housed in intensive care units where it can represent up to 15% of all nosocomial infections. We review the epidemiology of invasive caandidiasis in non-immunocompromaised, critically ill patients with special emphasis on disease trends over time, pathophysiology, diagnostic approach, risk factors, and impact. Recent epidemiological data suggesting that the emergence of non-albicans candidaa strains with reduced susceptibility to azoles, previously linked to the use of new antifungals for empiric and prophylactic therapy in immunocompromised patients, may not have occurred in the critically ill. Management of invasive candidiasis in these patients will be addressed in the December issue of The Lancet Infectious Diseases.
Helicobacter cinaedi is a rare pathogen in humans, occurring mostly in immuno-compromised patients, with a high potential for recurrence. We describe a case of a patient with lymphoma hospitalized ...for chemotherapy.
At admission, the patient presented with an indolent and non-prurigenic macular rash around her implantable venous access device. Gram staining of blood cultures revealed the presence of spiral-shaped gram-negative rods that could not be grown upon subculture. Helicobacter cinaedi was identified by PCR. No other symptoms or pathology were observed in a whole body CT scan. The implantable venous access device was removed and empiric therapy by ceftriaxone and gentamicin for 2 weeks was initiated, followed by peroral clarithromycin 2 x 500 mg/day and later by levofloxacin 2 x 500 mg/day for 7 weeks. Oncologic remission was achieved 3 months later. However, the patient was re-hospitalized 2 months later for fever, shivering, reappearance of the macular non-prurigenic rash, diarrhea, cough and asthenia. Blood cultures grew H. cinaedi. Multiple investigations could not identify the source. Empiric antibiotic therapy of ceftriaxone and doxycycline was started for 2 weeks with resolution of symptoms, followed by an oral combination of amoxicillin, metronidazole and doxycycline for 2 months; doxycycline was continued for another month. Bacteremia has not recurred for a period of 19 months.
Although H. cinaedi is considered to be a low virulent bacteria, its potential to cause recurrent bacteremia should not be underestimated. H. cinaedi could have an endovascular source of infection and should be treated for an adequate duration with combined antibiotherapy.
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