European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3--2009 update.

In 2005, several groups, including the European Group for Blood and Marrow Transplantation, the European Organization for Treatment and Research of Cancer, the European Leukemia Net and the Immunocompromised Host Society created the European Conference on Infections in Leukemia (ECIL). The main goal of ECIL is to elaborate guidelines, or recommendations, for the management of infections in leukemia and stem cell transplant patients. The first sets of ECIL slides about the management of invasive fungal disease were made available on the web in 2006 and the papers were published in 2007. The third meeting of the group (ECIL 3) was held in September 2009 and the group updated its previous recommendations. The goal of this paper is to summarize the new proposals from ECIL 3, based on the results of studies published after the ECIL 2 meeting: (1) the prophylactic recommendations for hematopoietic stem cell transplant recipients were formulated differently, by splitting the neutropenic and the GVHD phases and taking into account recent data on voriconazole; (2) micafungin was introduced as an alternative drug for empirical antifungal therapy; (3) although several studies were published on preemptive antifungal approaches in neutropenic patients, the group decided not to propose any recommendation, as the only randomized study comparing an empirical versus a preemptive approach showed a significant excess of fungal disease in the preemptive group.

Survey of aspergillosis in non-neutropenic patients in Swiss teaching hospitals.

Invasive aspergillosis (IA) is a live-threatening opportunistic infection that is best described in haematological patients with prolonged neutropenia or graft-versus-host disease. Data on IA in non-neutropenic patients are limited. The aim of this study was to establish the incidence, disease manifestations and outcome of IA in non-neutropenic patients diagnosed in five Swiss university hospitals during a 2-year period. Case identification was based on a comprehensive screening of hospital records. All cases of proven and probable IA were retrospectively analysed. Sixty-seven patients were analysed (median age 60 years; 76% male). Sixty-three per cent of cases were invasive pulmonary aspergillosis (IPA), and 17% of these were disseminated aspergillosis. The incidence of IPA was 1.2/10 000 admissions. Six of ten cases of extrapulmonary IA affected the brain. There were six cases of invasive rhinosinusitis, six cases of chronic pulmonary aspergillosis, and cases three of subacute pulmonary aspergillosis. The most frequent underlying condition of IA was corticosteroid treatment (57%), followed by chronic lung disease (48%), and intensive-care unit stays (43%). In 38% of patients with IPA, the diagnosis was established at autopsy. Old age was the only risk factor for post-mortem diagnosis, whereas previous solid organ transplantation and chronic lung disease were associated with lower odds of post-mortem diagnosis. The mortality rate was 57%.

[Lymphogranuloma venereum. An old disease in a new dress]. / Lymphogranuloma venereum. Eine alte Krankheit in neuem Kleid.

Lymphogranuloma venereum is a sexually transmitted disease caused by Chlamydia trachomatis, serotypes L1, L2 and L3. The classical clinical manifestation is a painful inguinal lymphadenopathy, resulting without treatment in severe complications. Over the last years, however, the emergence of massive ulcerative proctitis has been observed, especially in men who have sex with men. Because the clinical symptoms are unspecific, Chlamydia trachomatis should actively be looked for. Reliable and rapid molecular tests have now been established to diagnose lymphogranuloma venereum. The therapeutic recommendation is tetracycline for 3 weeks. We present 5 cases to illustrate this disease.

[A drug addict presenting with complicated tricuspid valve endocarditis]. / Komplikationsreiche Trikuspidalklappenendokarditis bei einem Drogenabhängigen.

The right-sided heart valves are affected in about 10% of patients with infective endocarditis. However, the tricuspid valve is the most frequently involved valve in intravenous drug users with infective endocarditis. When treated with antibiotics, the prognosis is considered favorable. Reported here is the case of a drug-addicted patient with polymicrobial (Staphylococcus aureus and Streptococcus pneumoniae) infective endocarditis of the tricuspid valve and a lethal outcome due to multiple organ failure. The indications and options to perform cardiac surgery in patients with infective endocarditis of the tricuspid valve are discussed.

Comparison of infectious complications during induction/consolidation chemotherapy versus allogeneic hematopoietic stem cell transplantation.

Induction/consolidation chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies are associated with treatment-related risks such as infections. The predominant types of infections are blood stream infections (BSIs) and respiratory tract infections. We prospectively compared infectious complications after induction/consolidation chemotherapy versus allogeneic HSCT in a directly comparable setting with both groups being hospitalized on the same ward. From July 2003 until June 2008, 492 hospitalizations of 321 patients took place; 237 chemotherapies and 255 HSCTs were performed. We observed 49 (20.7%) BSIs, 70 (29.5%) pneumonias and 11 (4.6%) probable or proven invasive mould infections in the chemotherapy group. In the HSCT group we detected 70 (27.5%) BSIs, 71 (27.8%) pneumonias and 14 (5.4%) probable or proven invasive mould infections. There was a trend toward more transfers to the intensive care unit (OR 1.61; 95%CI 0.95-2.72; P=0.074) and BSIs (OR 1.45; 95%CI 0.95-2.22; P=0.079) after HSCT; 44 (13.7%) patients died. In-hospital mortality was significantly higher in the HSCT group (OR 2.39; 95%CI 1.22-4.68; P=0.010). We conclude that the risk of pneumonia and invasive mould infection is comparable after induction/consolidation chemotherapy and allogeneic HSCT. However, there was a trend for more BSIs and intensive care unit stays and a higher mortality in the latter.

Secular trend and risk factors for antimicrobial resistance in Escherichia coli isolates in Switzerland 1997-2007.

BACKGROUND: Antibacterial resistance in Escherichia coli isolates of urinary infections, mainly to fluoroquinolones, is emerging. The aim of our study was to identify the secular trend of resistant E. coli isolates and to characterize the population at risk for colonization or infections with these organisms. PATIENTS AND METHODS: Retrospective analysis of 3,430 E.coli first isolates of urine specimens from patients admitted to the University Hospital Basel in 1997, 2000, 2003, and 2007. RESULTS: Resistance to ciprofloxacin, trimethoprim/sulfamethoxazole, and amoxicillin/clavulanate has increased over the 10-year study period (from 1.8% to 15.9%, 17.4% to 21.3%, and 9.5% to 14.5%, respectively). A detailed analysis of the 2007 data revealed that independent risk factors for ciprofloxacin resistance were age (5.3% < 35 years of age to 21.9% in patients > 75 years; odds ratio [OR] 1.29 per 10 years, 95% confidence interval [CI] 1.15-1.45, p < 0.001) and male gender (OR 1.59, 95% CI 1.05-2.41, p = 0.04). In contrast, nosocomial E. coli isolates were associated with lower odds of ciprofloxacin resistance (OR 0.51, 95% CI 0.28-0.67, p < 0.001). The frequency of resistant isolate rates was not influenced by the clinical significance (i.e., colonization vs urinary tract infection, UTI) or by whether the urine was taken from a urinary catheter. Importantly, the increase in ciprofloxacin resistance paralleled the increase in ciprofloxacin consumption in Switzerland (Pearson's correlation test R(2)= 0.998, p = 0.002). Of note, resistance was less frequent in isolates sent in by general practitioners. However, after adjustment for age and gender, only resistance against amoxicillin/clavulanate was found to be less frequent (OR 0.34, 95% CI 0.16-0.92, p = 0.03). CONCLUSION: Our study reveals that resistance rates have been increasing during the last decade. Published resistance rates may lack information due to important differences regarding age, gender, and probable origin of the isolates. Empirical therapy for UTI should be guided more on individual risk profile and local resistance data than on resistance data banks.

Outcome of influenza infections in outpatients after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Influenza can cause significant morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). The diagnostic methods and antiviral treatment have scarcely been investigated. METHODS: We retrospectively identified influenza-infected patients with upper or lower respiratory tract infection (RTI) diagnosed by culture and polymerase chain reaction (PCR) testing between November 2007 and April 2008. Treatment with oseltamivir 75 mg twice daily and serial nasal swabs were performed at the discretion of the treating physician. RESULTS: We identified 21 influenza infections in 19 patients: 19 with upper RTI and 2 with lower RTI. At diagnosis, all 21 samples were positive for PCR with a median influenza load of 5.9 log(10) copies/mL. Culture was positive in 14 (67%) patients. Influenza A virus was diagnosed in 8 (38%) episodes and influenza B virus in 13 (62%) episodes. Two patients were sequentially infected by influenza A, followed by B after 38 and 47 days, respectively. Eighteen (86%) patients were treated with oseltamivir for 11 days (median, interquartile range [IQR]: 8-14). No progression to lower RTI or mortality occurred. Shedding persisted for 12 days (median, IQR: 8-13). Absolute lymphocyte count at diagnosis correlated inversely with shedding of the virus (P<0.001). CONCLUSIONS: Oseltamivir is well tolerated and may reduce mortality of influenza virus-infected patients after HSCT. PCR may help to optimize diagnosis and to monitor treatment strategies.

Emergence of SCCmec type IV as the most common type of methicillin-resistant Staphylococcus aureus in a university hospital.

BACKGROUND: The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) has dramatically changed over the last decade by the emergence of community-associated MRSA (CA-MRSA). Recent studies indicate that these strains have already spread to hospitals. To evaluate if SCCmec type IV and Panton-Valentine leukocidin (PVL) are unambiguous markers of CA-MRSA, we analyzed 77 sporadic MRSA strains isolated, in our low MRSA incidence university hospital, from inpatients between 2000 and 2004. METHODS: MRSA strains were analyzed by staphylococcal cassette chromosome mmecec (SCCmec) typing, PCR for PVL genes and pulsed-field gel electrophoresis (PFGE). MRSA was classified in HA-MRSA or CA-MRSA according to Centers for Disease Control and Prevention (CDC) criteria. Antimicrobial susceptibility testing was performed using microbroth dilution method following CLSI recommendations. RESULTS: Among 77 sporadic single-patient strains, SCCmec types I-IV and four subtypes were identified. Type IV/IVA was most common (42.9%).The distribution of SCCmec types changed over the years. Type IV/IVA strains increased from 33.3% in 2000 to 57.9% in 2004. Type IV strains were resistant to ciprofloxacin in 81.8%, and in 9.1% to tobramycin while type IVA strains were 100% resistant to both antimicrobials. In contrast, non-type IV/IVA strains were resistant to ciprofloxacin in 86.4%, and in 75.0% to tobramycin. Only one strain was PVL positive and harbored SCCmec type III variant. By PFGE analysis, the 33 SCCmec type IV/IVA strains comprised 12 distinct genotypes. 36.4% of 11 CA-MRSA and 43.9% of 66 HA-MRSA harbored SCCmec type IV/IVA. CONCLUSION: Type IV/IVA has become the most common SCCmec type in inpatients of our university hospital. The SCCmec type IV/IVA is present in both CA-MRSA and HA-MRSA limiting its use as a marker for CA-MRSA.

[New Swiss guidelines for the prevention of infective endocarditis]. / Nouvelles recommandations suisses pour ola prophylaxie de l'endocardite infectieuse.

Following the publication of updated American guidelines in 2007, the 2000 Swiss guidelines for the prevention of endocarditis have been revised. These new guidelines are more restrictive than the former ones. They include fewer cardiac conditions and fewer invasive procedures. Only patients at high risk of adverse outcome in case of endocarditis should now receive antibiotics before some invasive procedures.

Highly effective regimen for decolonization of methicillin-resistant Staphylococcus aureus carriers.

OBJECTIVE: To evaluate the efficacy of a standardized regimen for decolonization of methicillin-resistant Staphylococcus aureus (MRSA) carriers and to identify factors influencing decolonization treatment failure. DESIGN: Prospective cohort study from January 2002 to April 2007, with a mean follow-up period of 36 months. SETTING: University hospital with 750 beds and 27,000 admissions/year. PATIENTS: Of 94 consecutive hospitalized patients with MRSA colonization or infection, 32 were excluded because of spontaneous loss of MRSA, contraindications, death, or refusal to participate. In 62 patients, decolonization treatment was completed. At least 6 body sites were screened for MRSA (including by use of rectal swabs) before the start of treatment. INTERVENTIONS: Standardized decolonization treatment consisted of mupirocin nasal ointment, chlorhexidine mouth rinse, and full-body wash with chlorhexidine soap for 5 days. Intestinal and urinary-tract colonization were treated with oral vancomycin and cotrimoxazole, respectively. Vaginal colonization was treated with povidone-iodine or, alternatively, with chlorhexidine ovula or octenidine solution. Other antibiotics were added to the regimen if treatment failed. Successful decolonization was considered to have been achieved if results were negative for 3 consecutive sets of cultures of more than 6 screening sites. RESULTS: The mean age (+/- standard deviation [SD]) age of the 62 patients was 66.2 +/- 19 years. The most frequent locations of MRSA colonization were the nose (42 patients [68%]), the throat (33 [53%]), perianal area (33 [53%]), rectum (36 [58%]), and inguinal area (30 [49%]). Decolonization was completed in 87% of patients after a mean (+/-SD) of 2.1 +/- 1.8 decolonization cycles (range, 1-10 cycles). Sixty-five percent of patients ultimately required peroral antibiotic treatment (vancomycin, 52%; cotrimoxazole, 27%; rifampin and fusidic acid, 18%). Decolonization was successful in 54 (87%) of the patients in the intent-to-treat analysis and in 51 (98%) of 52 patients in the on-treatment analysis. CONCLUSION: This standardized regimen for MRSA decolonization was highly effective in patients who completed the full decolonization treatment course.

Hepatitis with fibrin-ring granulomas.

We describe a 66-year-old woman hospitalized with fever, fatigue and hepatopathy. In her medical history arterial hypertension (treated with propranolol and lisinopril), diabetes mellitus type 2 (no treatment before admission) and a gout arthropathy were noted wherefore a therapy with allopurinol 300 mg per day has been started 4 months before. Liver biopsy revealed fibrin-ring granulomas, compatible with allopurinol-induced hepatitis. Because of persistence of high fever after stopping allopurinol, steroids (1 mg/kg) were started. Under this treatment, she developed pancytopenia and fever. The bone marrow aspiration revealed Leishmania infantum. A second liver biopsy showed amastigotes and a disappearance of the granulomas. The history revealed a travel to Malta 2 years earlier. Despite adequate treatment with liposomal amphotericin B the patient deteriorated and finally died in septic shock.

Candida krusei--a serious complication in patients with hematological malignancies: successful treatment with caspofungin.

Candida krusei infections are serious complications in neutropenic patients with hematological malignancies. We report the successful treatment of C. krusei infection with caspofungin in 3 allogeneic hematopoietic stem cell transplant recipients and 1 patient with induction chemotherapy for acute myeloid leukemia.

Visceral leishmaniasis: a threat to immunocompromised patients in non-endemic areas?

Visceral leishmaniasis is rare in western Europe, but may be life-threatening in immunocompromised patients. It is therefore important to understand the incidence of the disease in a non-endemic area and its relationship with immunosuppressive conditions. Between 1990 and 2005, 12 patients were diagnosed with leishmaniasis at Basel University Hospital, Switzerland. Eleven presented with visceral symptoms and ten had an underlying immunosuppressive condition. Since increasing numbers of immunosuppressed patients have a history of travel to endemic countries, an association of visceral leishmaniasis with cellular immunosuppression (other than that associated with human immunodeficiency virus) might become more frequent in non-endemic areas.

Vertebral osteomyelitis caused by Actinobaculum schaalii: a difficult-to-diagnose and potentially invasive uropathogen.

We report the first case of vertebral osteomyelitis caused by Actinobaculum schaalii and review all cases of A. schaalii identified at our institution between 2002 and 2005. A. schaalii causes urinary tract infections - especially in elderly people - occasionally with septic complications.

[Mycobacterium avium pneumonia in an HIV negative patient]. / Mycobacterium-avium-Pneumonie bei HIV-negativem Patienten.

A 79-year-old patient was admitted with fever and shortness of breath. His medical history included treatment for lung cancer 3 years previously. The patient's clinical and radiological status remained unchanged despite antibiotic treatment for pneumonia. No infectious pathogen could be identified. Treatment with systemic steroids for suspected cryptogenic organizing pneumonitis (COP) was started. Following steroid treatment the patient's shortness of breath ameliorated and C-reactive protein was normal. Three weeks after admission Mycobacterium avium complex (MAC) grew in sputa cultures and therefore a diagnosis of MAC pneumonia was made.

[Diagnostic procedures for patients with community acquired pneumonia]. / Diagnostik bei ambulant erworbener Pneumonie.

The diagnosis of community acquired pneumonia (CAP) is based on a patient history with respiratory symptoms and additional symptoms and signs such as fever over more than 4 days, dyspnea and tachypnea and/or a positive lung auscultation. Despite recently developed tests, radiology is a key diagnostic procedure for confirming CAP. Importantly, the first treating physician must judge whether to hospitalize a patient or not. Two major scoring systems allow judgement of severity and short-term prognosis. In general, in patients with mild or moderate pneumonia who can be treated on an ambulatory basis, no specific microbiological diagnosis must be performed. If, for clinical or epidemiological reasons a gram stain is done, it must be obtained from purulent sputum. Recent tests may help in discriminating between viral and bacterial pneumonia (procalcitonin test) or determine the bacteria responsible for acute disease (pneumococcal antigen test using urine).

[Nosocomial urinary tract infection in adults]. / Nosokomiale Harnwegsinfektionen des Erwachsenen.

Urinary tract infection (UTI) is the most common infection in hospitalized adults. Nosocomial UTIs are mainly associated with the use of urinary catheters. Thus, the decision for catheterization should be made carefully and catheters removed in time. In order to prevent unnecessary antibiotic use in patients with urinary catheters correct diagnosis is crucial. Chinolones, broad-spectrum penicillins and third-generation cephalosporins are the mainstay of therapy. Comorbidities should be considered and potential obstructions of urinary flow removed. Economically important are the normally higher prices of i.v. antibiotics compared to oral use.

[Dangerous fever]. / Bedrohliches Fieber.

Fever is a frequent symptom which can arise as a consequence of bacterial, viral and parasitic infections. Additionally, fever is a frequent symptom in non-infectious diseases, e.g. autoimmune diseases or lymphomas. The term dangerous fever describes febrile conditions which are associated with high mortality and, in most cases, mandate hospitalization, and even monitoring in an intensive care unit. As a rule, infections (bacterial infections in particular) may begin harmlessly; however, they can instantaneously change into life-threatening conditions even a few days later. In the following report we focus on some critical syndromes which must be recognized quickly, such as severe sepsis, septic shock, fever in neutropenia, and fever in the immunocompromised patient.

[Atypical erythema induratum Bazin with tuberculous osteomyelitis]. / Atypisches erythema induratum Bazin bei tuberkulöser osteomyelitis.

Diagnosis of all types of cutaneous tuberculosis is challenging because the clinical picture of these diseases is highly variable. We describe the case of a 79-year old woman with an atypical presentation of Erythema induratum Bazin (EIB) on the chest and left arm in association with a tuberculous osteomyelitis of the left olecranon. Surprisingly, M. tuberculosis grew also from biopsies of the EIB-lesions. This contradicts the conventional view that considers EIB (a tuberculid) to be caused by a hypersensitivity reaction to mycobacteria. The presented case supports the hypothesis that EIB may also be caused by hematogenous or lymphatic spread of viable M. tuberculosis.