We read with interest the recent network meta-analysis published by Horita et al. comparing different β-lactams in the empirical treatment of febrile neutropenia (FN) [[1]Horita N. Shibata Y. Watanabe H. Namkoong H. Kaneko T. Comparison of antipseudomonal β-lactams for febrile neutropenia empiric therapy: systematic review and network meta-analysis.Clin Microbiol Infect. 2017; 23: 723-729Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar]. We consider that the authors draw debatable conclusions that could encourage unjustifiably wide use of imipenem/cilastatin in individuals with FN. Another meta-analysis, published in 2010 [[2]Paul M. Yahav D. Bivas A. Fraser A. Leibovici L. Anti-pseudomonal β-lactams for the initial, empirical, treatment of febrile neutropenia: comparison of β-lactams.Cochrane Database Syst Rev. 2010; : CD005197PubMed Google Scholar] on the same issue, drew different conclusions, showing lower all-cause mortality with piperacillin/tazobactam versus cefepime or carbapenems. Several reasons can explain these different findings. Most obviously, some studies included by Horita et al., simply post-dated Paul et al.; but, perhaps more importantly, the newly available studies included by Horita et al. are often from high-resistance countries and often analysed piperacillin/tazobactam, whereas much of the imipenem/cilastatin data come from relatively old studies. As resistance varies with place and time, these factors have major potential impact. Overall, 15 studies representing 4026 patients and comparing piperacillin/tazobactam with other antibiotics were included in Horita et al.’s meta-analysis, but not in that of Paul et al.; ten of these were published since 2010, variously originating from Turkey, India, Japan, China and Spain. A recent multinational study of bacteraemia in individuals undergoing haematopoietic stem cell transplants found significantly higher rates of resistance to non-carbapenem β-lactams among Gram-negative rods (GNRs) isolated from patients in southeast Europe (55.3%) or China (76%) versus those in northwest Europe (27.6%) [[3]Averbuch D. Tridello G. Hoek J. Mikulska M. Akan H. Yanez San Segundo L. et al.Antimicrobial resistance in gram-negative rods causing bacteremia in haematopoietic stem cell transplant patients: intercontinental prospective study of Infectious Diseases Working Party of the European Bone Marrow Transplantation group.Clin Infect Dis. 2017; 65: 1819-1828Crossref PubMed Scopus (128) Google Scholar]. In this study, 33.9%, 56.5% and 52.0% of GNR reported from Spain, Turkey and China, respectively, were resistant to non-carbapenem anti-Pseudomonas penicillin β-lactamase inhibitors. In an Indian study, fully 82.7% of Escherichia coli and 74.3% of Klebsiella spp. isolated from individuals with cancer were extended spectrum β-lactamase producers [[4]Abdul K. Vidyalakshmi P. Jayalakshmi V. Poojary I. Susceptibility profile of gram-negative bacteremic isolates to β lactam-β lactamase inhibitor agents in comparison to other antibiotics.Indian J Cancer. 2014; 51: 450-452Crossref PubMed Scopus (2) Google Scholar]. One would expect to see an advantage for imipenem/cilastatin over other β-lactams at sites with such high rates of resistance, where empirical treatment with piperacillin/tazobactam may be insufficient. Basing the approach to FN on local epidemiology is crucial. In our recent study in haematopoietic stem cell transplant patients, a half of GNR were resistant to non-carbapenem β-lactams [[3]Averbuch D. Tridello G. Hoek J. Mikulska M. Akan H. Yanez San Segundo L. et al.Antimicrobial resistance in gram-negative rods causing bacteremia in haematopoietic stem cell transplant patients: intercontinental prospective study of Infectious Diseases Working Party of the European Bone Marrow Transplantation group.Clin Infect Dis. 2017; 65: 1819-1828Crossref PubMed Scopus (128) Google Scholar]; however, the rates in individual countries ranged from 0% to 100%. Underpinning the high rates of resistance among GNRs in some parts of the world are changes in the global molecular epidemiology, mainly since 2000, notably including the proliferation of Escherichia coli ST131 and the common co-presence of CTX-M-15 (an extended spectrum β-lactamase) with OXA-1/30 (a sulphone/clavam-resistant penicillinase) enzymes in this and other Enterobacteriaceae. In some European regions, over 50% of bloodstream E. coli isolates were reported to be resistant to third-generation cephalosporins in the 2016 WHO Antimicrobial Resistance report (http://www.euro.who.int/__data/assets/pdf_file/0005/354434/WHO_CAESAR_AnnualReport_2017.pdf?ua=1). Piperacillin/tazobactam may be less effective in this situation and most (19/23) of these studies assessing piperacillin/tazobactam in Horita et al.’s meta-analysis were published after 2000. Ten studies included in Horita et al.’s meta-analysis compared imipenem/cilastatin to other antibiotics; these included 2156 patients. Seven of these studies (1496 patients, 70%) were published between 1990 and 2004, before the global spread of carbapenem-resistant Enterobacteriaceae. Several countries have, largely since 2007, seen proliferation of carbapenemases, though the predominant types (KPC, OXA-48, VIM, NDM or IMP) vary with the particular country. Thirteen of the 50 studies selected by Horita et al. were published between 1990 and 2000. Significant changes occurred in bacterial resistance since 90s to present day. This is a common problem of network meta-analysis on antibacterials, where efficacy may change with time and place. In simple language, this means that one must be very wary of statistical comparison of agents that were not compared head-to-head in the same time and place. In the present case, mortality data on imipenem, based on studies mainly published before the emergence of carbapenem-resistance, are compared with mortality data on piperacillin/tazobactam based on more recent studies, mainly from countries with high rates of extended spectrum β-lactamase infections. Another concern is the dosing regimens of β-lactams, which was not considered in Horita et al.’s meta-analysis. Individuals with FN have an increased volume of distribution and increased clearance, resulting in a decreased time above MIC. Therefore, using a maximal dosage is crucial. In the studies selected by Horita et al., piperacillin/tazobactam was dosed at 4.5 g thrice daily in 6/23 studies and 24% of the patients, and meropenem was dosed at ≤2 g/day (in adults) in 2/14 studies and 24% of the patients. These regimens, which were not enhanced by prolonged/continuous infusion, may be insufficient. The authors' conclusion that ‘Among guideline-recommend medications, imipenem/cilastatin was related to the highest treatment success rate and the lowest all-cause death’ may encourage preferential use of imipenem/cilastatin as the primary choice for any FN. However, no significant differences were reported according to the primary end point (treatment success without modification) between cefepime, meropenem, imipenem/cilastatin and piperacillin/tazobactam, nor for a secondary end point (all-cause death) between meropenem, imipenem/cilastatin, ceftazidime and piperacillin/tazobactam. Moreover, there are no significant differences in the spectrum of coverage between meropenem and imipenem/cilastatin. In conclusion, the ECIL group wishes to reiterate its previous position that, although we have no doubt as to the efficacy and safety profile of imipenem/cilastatin in patients with FN, carbapenems should, whenever possible, be avoided in individuals without severe clinical presentation and risk factors for bacterial resistance to other agents, so as to preserve their activity [[5]Averbuch D. Orasch C. Cordonnier C. Livermore D.M. Mikulska M. Viscoli C. et al.European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia.Haematologica. 2013; 98: 1826-1835Crossref PubMed Scopus (351) Google Scholar]. The wide range of resistance rates among GNRs in different countries warrants a customized approach in patients with FN, combined with rigorous infection control in settings where resistance has become or is becoming prevalent. Universal deployment of carbapenems without de-escalation in all individuals with FN, half of whom have neither clinical nor microbiological infection, is only likely to lead to an increase in carbapenem-resistant infections, and should be discouraged. DA, CO, MM, IG, WK, GK, OM, DE, MA, TC and CC reported no conflicts of interests. DL and CV reported on the conflicts of interests outside the submitted work in the COI form attached. No funding was received for this manuscript.

We read with interest the Note by Micol et al. [1] challenging ECIL's recommendation to discontinue empirical antibiotics after resolution of fever of unknown origin (FUO) in high-risk haematologic patients despite persistent neutropenia. We reply for the ECIL panel, whose guidance states thatempiric antibiotics can be discontinued after ≥72 hours . . . in [FUO] patients who have been hemodynamically stable since presentation and . . . afebrile for ≥48 hours, irrespective of their neutrophil count or expected duration of neutropenia (BII).

We report the case of a 37-year-old previously healthy woman diagnosed with a breast abscess due to Propionibacterium avidum after breast reduction surgery. This case emphasizes the potential pathogenicity and morbidity associated with this commensal skin organism.

We analyzed the species distribution of Candida blood isolates (CBIs), prospectively collected between 2004 and 2009 within FUNGINOS, and compared their antifungal susceptibility according to clinical breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013, and the Clinical and Laboratory Standards Institute (CLSI) in 2008 (old CLSI breakpoints) and 2012 (new CLSI breakpoints). CBIs were tested for susceptiblity to fluconazole, voriconazole and caspofungin by microtitre broth dilution (Sensititre® YeastOne™ test panel). Of 1090 CBIs, 675 (61.9%) were C. albicans, 191 (17.5%) C. glabrata, 64 (5.9%) C. tropicalis, 59 (5.4%) C. parapsilosis, 33 (3%) C. dubliniensis, 22 (2%) C. krusei and 46 (4.2%) rare Candida species. Independently of the breakpoints applied, C. albicans was almost uniformly (>98%) susceptible to all three antifungal agents. In contrast, the proportions of fluconazole- and voriconazole-susceptible C. tropicalis and F-susceptible C. parapsilosis were lower according to EUCAST/new CLSI breakpoints than to the old CLSI breakpoints. For caspofungin, non-susceptibility occurred mainly in C. krusei (63.3%) and C. glabrata (9.4%). Nine isolates (five C. tropicalis, three C. albicans and one C. parapsilosis) were cross-resistant to azoles according to EUCAST breakpoints, compared with three isolates (two C. albicans and one C. tropicalis) according to new and two (2 C. albicans) according to old CLSI breakpoints. Four species (C. albicans, C. glabrata, C. tropicalis and C. parapsilosis) represented >90% of all CBIs. In vitro resistance to fluconazole, voriconazole and caspofungin was rare among C. albicans, but an increase of non-susceptibile isolates was observed among C. tropicalis/C. parapsilosis for the azoles and C. glabrata/C. krusei for caspofungin according to EUCAST and new CLSI breakpoints compared with old CLSI breakpoints.

Disorders of local immunity associated with diabetes, neuropathy, vascular disease and pressure lesions all contribute to the pathogenesis of diabetic foot lesions. Diabetic foot infections are frequently encountered, comprising multifactorial pathology and high morbidity and mortality rates. Microbiological sampling is indicated only when infection is suspected clinically, that is, when a lesion presents a minimum of two of the following six signs: erythema, heat, pain, tumefaction, induration or purulent discharge.

OBJECTIVES:Smoking is the most prevalent modifiable risk factor for cardiovascular diseases among HIV-positive persons. We assessed the effect on smoking cessation of training HIV care physicians in counselling. METHODS:The Swiss HIV Cohort Study (SHCS) is a multicentre prospective observational database. Our single-centre intervention at the Zurich centre included a half day of standardized training for physicians in counselling and in the pharmacotherapy of smokers, and a physicians' checklist for semi-annual documentation of their counselling. Smoking status was then compared between participants at the Zurich centre and other institutions. We used marginal logistic regression models with exchangeable correlation structure and robust standard errors to estimate the odds of smoking cessation and relapse. RESULTS:Between April 2000 and December 2010, 11 056 SHCS participants had 121 238 semi-annual visits and 64 118 person-years of follow-up. The prevalence of smoking decreased from 60 to 43%. During the intervention at the Zurich centre from November 2007 to December 2009, 1689 participants in this centre had 6068 cohort visits. These participants were more likely to stop smoking [odds ratio (OR) 1.23; 95% confidence interval (CI) 1.07-1.42; P=0.004] and had fewer relapses (OR 0.75; 95% CI 0.61-0.92; P=0.007) than participants at other SHCS institutions. The effect of the intervention was stronger than the calendar time effect (OR 1.19 vs. 1.04 per year, respectively). Middle-aged participants, injecting drug users, and participants with psychiatric problems or with higher alcohol consumption were less likely to stop smoking, whereas persons with a prior cardiovascular event were more likely to stop smoking. CONCLUSIONS:An institution-wide training programme for HIV care physicians in smoking cessation counselling led to increased smoking cessation and fewer relapses.

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.

Endotoxine können durch Stimulation der entsprechenden Rezeptoren zur Produktion von fieberauslösenden Zytokinen führen. Dazu gehören als wichtigste Vertreter Interleukin (IL) 1 und 6, der Tumornekrosefaktor (TNF) sowie Interferon (IFN)-a. Die Produktion dieser Zytokine kann jedoch auch durch Entzündungen, Traumata oder Antigen-Antikörper-Komplexe stimuliert werden. Virale Infektionen führen durch die Infektion körpereigener Zellen zur Produktion pyrogener Zytokine. IL-1, IL-6 und TNF induzieren die Synthese von Prostaglandin 2, welches im Hypothalamus den thermostatischen Richtwert der Körpertemperatur erhöht und in der Peripherie unspezifische Myalgien und Arthralgien – häufige Begleitsymptome von Fieber – verursacht (Abb. 1 x). Es gibt einige Berichte über den günstigen Effekt von Fieber bei Tieren mit Infektionskrankheiten. Jedoch konnte bislang in keiner Studie gezeigt werden, dass Fieber an sich die Erholung von Infektionskrankheiten begünstigt oder als Unterstützung des Immunsystems dient. Einige positive und negative Aspekte von Fieber sind in Tabelle 1 p zusammengestellt. Somit bleibt die Frage offen, ob Fieber nützlich ist. Die Behandlung von Fieber und seinen Symptomen schadet jedoch nicht und führt zu keiner Verzögerung der Heilung bakterieller oder viraler Infektionen. Klar ist jedoch, dass Fieber ein Symptom gefährlicher und lebensbedrohlicher Infektionskrankheiten sein kann, die ohne frühzeitige Erkennung und Behandlung eine hohe Mortalität aufweisen. Darauf möchten wir im Folgenden näher eingehen.

We report the difficulties encountered in diagnosing leptospirosis in an 85-year-old man who presented with non-specific signs and symptoms. Initially, a wide haematologic and oncologic work-up without significant results was performed, as symptoms of several organ dysfunctions emerged and the clinical course showed a rapid deterioration. After several days without a definite diagnosis, the infection was finally detected after reviewing all results and considering the patient’s profession as a farmer. After receiving appropriate antibiotic treatment the patient recovered fully.

Wir beschreiben einen Patienten mit später HIV-Präsentation, Meningitis tuberculosa und offener Lungentuberkulose bei Miliartuberkulose unter schwerer HIV-assoziierter Immunsuppression. Im Verlauf tritt eine weitere opportunistische Infektion (Pneumocystis-jiroveci-Pneumonie) und im Rahmen der antiretroviralen Therapie ein Immunrekonstitutionssyndrom (IRIS) auf. Letzteres führt zu weiteren Organmanifestationen der Miliartuberkulose (urogenital, gastrointestinal). Mit der späten HIV-Präsentation assoziierte Probleme sind opportunistische Infektionen und das IRIS zu Beginn der antiretroviralen Therapie. Die Wahl des Behandlungszeitpunkts der HIV-Infektion bei gleichzeitiger opportunistischer Infektion ist entscheidend.

We report the case of a 81-year-old, immunocompromised Patient, admitted to our hospital with new-onset headaches and word-finding difficulties. The MRI of the brain revealed a temporal mass on the left with marginal contrast-enhancement. During the next days Listeria monocytogenes grew in the bloodcultures so that the diagnosis of a brain-abscess caused by Listeria was established. Due to the localisation, surgical drainage of the abscess was not possible, so that a prolonged antibiotic therapy lasting over 4.5 months was initiated. The MRI after therapy demonstrated no abscess persistence. Listeria mostly cause infections in the immunocompromised, elderly, newborn or pregnant host. Next to bacteraemia without a focus, CNS-invasion with meningitis, meningoencephalitis or less frequent abcess-formation (5-10%) is the most important manifestation.

La borréliose de Lyme est une maladie transmise par des tiques (vecteurs), dont le pathogène, Borrelia burgdorferi, fait partie du groupe des spirochètes. C’est en 1975 qu’elle a été décrite pour la première fois, et son nom est celui de la ville de Lyme, Connecticut, zone d’endémie. En Amérique du Nord, seule Borrelia burgdorferi sensu stricto (transmise par Ixodes scapularis) est présente, accompagnée en Europe par Borrelia garinii et Borrelia afzelii (transmises par Ixodes ricinus). Ces trois espèces sont réunies sous l’appellation Borrelia burgdorferi sensu lato. Du fait que plusieurs organes sont atteints et que les stades de la maladie peuvent se chevaucher, ses manifestations cliniques sont multiples et le diagnostic différentiel est vaste. Aucune de ses mani festations n’est pathognomonique et il n’y a pas de gold standard microbiologique. C’est pourquoi le diagnostic de borréliose de Lyme ne peut être posé qu’avec l’anamnèse, le tableau clinique et les ana lyses de laboratoire. Les différences biologiques entre borrélies des Etats-Unis et d’Europe ont leur influence sur plusieurs aspects de la borréliose de Lyme. Tout ce qui est valable pour les Etats-Unis ne l’est pas nécessairement pour la borréliose de Lyme euro péenne; et ce que dit la littérature américaine sur la borréliose de Lyme ne doit être appliqué qu’avec prudence en Europe ou en Suisse. Cet article donne un aperçu de l’épidémiologie, de la clinique, du diagnostic et du traitement de la borréliose de Lyme en Suisse.

Die Lyme-Borreliose ist eine durch Zecken (Vektor) übertragene Krankheit, deren Erreger, Borrelia burgdorferi, zur Gruppe der Spirochäten gehören. 1975 wurde sie erstmals beschrieben und nach der Stadt Lyme in Connecticut, einem Endemiegebiet, benannt. In Nordamerika kommt nur die Spezies Borrelia burgdorferi sensu stricto (übertragen von Ixodes scapularis) vor, in Europa zusätzlich Borrelia garinii und Borrelia afzelii (übertragen von Ixodes ricinus). Die drei Arten Borrelia burgdorferi sensu stricto, Borrelia garinii und Borrelia afzelii werden unter Borrelia burgdorferi sensu lato zusammengefasst. Weil verschiedene Organsysteme betroffen sind und die Krankheitsstadien überlappen können, sind die klinischen Manifestationsformen vielfältig und die Differentialdiagnose breit. Keine der Manifestationen ist pathognomonisch, und ein mikrobiologischer Goldstandard fehlt. Deshalb kann die Diagnose einer Lyme-Borreliose nur unter Berücksichtigung von Anamnese, klini schem Bild und Laboranalysen gestellt werden. Die biologischen Unterschiede der Borrelien in den USA und Europa haben auf verschiedene Aspekte der Lyme-Borreliose einen Einfluss. Deshalb kann bei der europäischen Lyme-Borreliose nicht eins zu eins auf alle in den USA gewonnenen Erkenntnisse zurückgegriffen werden, und die amerikanische Literatur zur Lyme-Borreliose ist nur mit Vorsicht auf Europa bzw. die Schweiz zu übertragen. Dieser Artikel gibt einen Überblick hinsichtlich Epi demiologie, Klinik, Abklärung und Therapie der Lyme-Borreliose in der Schweiz.