Identification of Streptococcus pneumoniae in hospital-acquired pneumonia in adults.

Hospital-acquired pneumonia (HAP) is often more severe and life-threatening than community-acquired pneumonia (CAP). The role of Streptococcus pneumoniae in CAP is well-understood, but its role in HAP is unclear. The objective of this study was to summarize the available literature on the prevalence of S. pneumoniae in HAP episodes. We searched MEDLINE for peer-reviewed articles on the microbiology of HAP in individuals aged ≥18 years, published between 2008 and 2018. We calculated pooled estimates of the prevalence of S. pneumoniae in episodes of HAP using a random-effects, inverse-variance-weighted meta-analysis. Forty-seven of 1908 articles met the inclusion criteria. Bacterial specimen isolation techniques for microbiologically defined HAP episodes included bronchoalveolar lavage, protective specimen brush, tracheobronchial aspirate and sputum, as well as blood culture. Culture was performed in all studies; five studies also used urine antigen detection (5/47; 10.6%). S. pneumoniae was identified in 5.1% (95% confidence interval (CI): 3.8-6.6%) of microbiologically defined HAP episodes (N = 20), with 5.4% (95% CI: 4.3-6.7%, N = 29) in ventilator-associated HAP and 6.0% (95% CI: 4.1-8.8%, N = 6) in non-ventilator-associated HAP. S. pneumoniae was identified in 5.3% (95% CI: 4.5-6.3%) of HAP occurring in the intensive care unit (ICU, N = 41) and in 5.6% (95% CI: 3.3-9.5%, N = 5) outside the ICU. A higher proportion of early-onset HAP (10.3%; 95% CI: 8.3-12.8%, N = 16) identified S. pneumoniae as compared with late-onset HAP (3.3%; 95% CI: 2.5-4.4%, N = 16). In conclusion, S. pneumoniae was identified by culture in 5.1% of microbiologically defined HAP episodes. The importance of HAP as part of the disease burden caused by S. pneumoniae merits further research.

Time-dependent differences in management and microbiology of orthopaedic internal fixation-associated infections: an observational prospective study with 229 patients.

OBJECTIVES: Little information has been published on orthopaedic internal fixation-associated infections. We aimed to analyse time-dependent microbiology, treatment, and outcome. METHODS: Over a 10-year period, all consecutive patients with internal fixation-associated infections at the University Hospital of Basel, were prospectively followed and clinical, microbiological and outcome data were acquired. Infections were classified as early (0-2 weeks after implantation), delayed (3-10 weeks), and late (>10 weeks). RESULTS: Two hundred and twenty-nine patients were included, with a median follow-up of 773 days (IQR 334-1400). Staphylococcus aureus was the most prevalent pathogen (in 96/229 patients, 41.9%). Enterobacteriaceae were frequent in early infections (13/49, 26.5%), whereas coagulase-negative staphylococci (36/92, 39.1%), anaerobes (15/92, 16.3%) and streptococci (10/92, 10.9%) increased in late revisions. Failure was observed in 27/229 (11.7%). Implants were retained in 42/49 (85.7%) in early, in 51/88 (57.9%) in delayed, and in 9/92 (9.8%) in late revisions (p < 0.01). Early revisions failed in 6/49 (12.2%), delayed in 9/88 (10.2%), and late in 11/92 (13.0%) (p 0.81). Debridement and retention failed in 6/42 (14.3%) for early, in 6/51 (11.8%) for delayed, and in 3/9 (33.3%) for late revisions (p 0.21). Biofilm-active antibiotic therapy tailored to resistance correlated with improved outcome for late revisions failure (6/72, 7.7% versus 6/12, 50.0%; p < 0.01) but not for early revisions failure (5/38, 13.2% versus 1/11, 9.1%; p 1.0). CONCLUSIONS: Treatment of internal fixation-associated infections showed a high success rate of 87-90% over all time periods. Implant retention was highly successful in early and delayed infections but only limited in late infections.

Secular trends of bloodstream infections during neutropenia in 15 181 haematopoietic stem cell transplants: 13-year results from a European multicentre surveillance study (ONKO-KISS).

OBJECTIVES: Antibacterial resistance is emerging in patients undergoing haematopoietic stem cell transplantation (HSCT), and most data on the epidemiology of bloodstream infections (BSI)-causing pathogens come from retrospective single-centre studies. This study sought to investigate trends in the epidemiology of BSI in HSCT patients from a prospective multicentre cohort. METHODS: We investigated changes in the incidence of causative organisms of BSI during neutropenia among adult HSCT patients for 2002-2014. The data were collected from a prospective cohort for infection surveillance in 20 haematologic cancer centres in Germany, Austria and Switzerland (ONKO-KISS). RESULTS: A total of 2388 of 15 181 HSCT patients with neutropenia (1471 allogeneic (61.6%) and 917 autologous (38.4%) HSCT) developed BSI (incidence 15.8% per year). The incidence of Gram-negative BSI increased over time both in patients after allogeneic HSCT (allo-HSCT) and autologous HSCT (auto-HSCT). BSI caused by Escherichia coli in allo-HSCT patients increased from 1.1% in 2002 to 3.8% in 2014 (3/279 vs. 31/810 patients, p <0.001), and the incidence of BSI caused by enterococci increased from 1.8% to 3.3% (5 vs. 27 patients, p <0.001). In contrast, the incidence of BSI due to coagulase-negative staphylococci decreased in allo-HSCT patients from 8.2% to 5.1%, (23 vs. 40 patients, p <0.001) and in auto-HSCT patients from 7.7% to 2.0% (13/167 vs. 30/540 patients; p = 0.028 for period 2002-2011). No significant trends were observed for the incidence of BSI due to methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci or extended-spectrum ß-lactamase-producing Enterobacteriaceae. The BSI case fatality remained unchanged over the study period (total of 477 fatalities, 3.1%). CONCLUSIONS: The incidence of Gram-negative BSI significantly increased over time in this vulnerable patient population, providing evidence for reevaluating empiric therapy for neutropenic fever in HSCT patients.

[Update pneumococcal infections]. / Pneumokokkeninfektionen--was gibt es Neues?

Pneumococci remain the most important cause for community-acquired pneumonia. The colonization of the nasopharynx is prerequisite for their transmission and the colonization of toddlers are an important reservoir also for infections in the elderly. Since pneumococcal conjugate vaccines reduce the colonization rate of children its widespread use has also resulted in a reduction of invasive pneumococcal disease in adults. Advanced age and comorbidity are the most important risk factors for pneumococcal pneumonia and the mortality in this risk group is still very high. The strongest risk factor for invasive pneumococcal infections, however, is HIV/AIDS and solid or hematologic malignancies. A more rapid identification could aid de-escalation of empiric antibiotic therapy. The pneumococcal urinary antigen test, however lacks sensitivity for this purpose. In contrast, the direct identification of pathogens from positive blood culture bottles by MALDI-TOF is a very encouraging development in diagnostic microbiology. In several cohort studies patients treated with a combination of a betalactam plus macrolide had a lower mortality than patients treated with betalactam monotherapy. If these observations reflect a truly beneficial effect of combination therapy or rather confounding of the studies remains unclear and evidence from interventional studies is needed.

Detection of opsonic antibodies against Enterococcus faecalis cell wall carbohydrates in immune globulin preparations.

Three different commercially available polyvalent immune globulins (IG) were investigated for the existence of antibodies against cell wall carbohydrates of four different E. faecalis serotypes (using a cell wall carbohydrate-enzyme-linked immunosorbent assay), and whether these antibodies mediated opsonic killing (using an opsonic-killing assay). All three IG preparations contained antibodies against all four serotypes (CPS-A to CPS-D). However, only one of the three IG preparations showed opsonic killing against all four serotypes. Average killing was higher against serotypes A and B (72 and 79 %, respectively) than against serotypes C and D (30 and 37 %, respectively). Such IG preparations could play a role as an adjuvant therapeutic option in life-threatening infections with E. faecalis, particularly when resistant strains are involved.

Rapidly progressive hepatic alveolar echinococcosis in an ABO-incompatible renal transplant recipient.

We report on the case of an ABO-incompatible renal re-transplant recipient maintained on an intensified immunosuppressive regimen for recurrent cellular rejection episodes and transplant glomerulopathy who presented with rapidly growing hepatic tumors, radiologically suggestive of hemangiosarcoma. Upon resection and pathological work-up, the lesions revealed alveolar echinococcosis, a rare but potentially life-threatening parasitosis. Usually infection with Echinococcus multilocularis remains asymptomatic for extended periods of time and can go unrecognized for years. In the case presented, we observed an atypically rapid growth pattern of E. multilocularis that might have been due to the extent of the immunosuppressive regimen, which included repetitive anti-CD20 treatments. Retrospectively performed serological studies with enzyme-linked immunosorbent assays known to provide high sensitivity and specificity for the detection of echinococcosis in the general population, yielded ambiguous results in our immunocompromised host, which could be, in part, explained by B-cell depletion and its effects on antibody production and indirect actions on cellular immunity. In conclusion, this is the first report to our knowledge of hepatic alveolar echinococcosis in a renal transplant recipient. This case documents an altered clinical course of the parasitosis and the challenge of serological diagnostic tools under an intensified regimen of immunosuppressive agents, including rituximab.

Enterococcal surface protein contributes to persistence in the host but is not a target of opsonic and protective antibodies in Enterococcus faecium infection.

Enterococci are important nosocomial pathogens with multiple intrinsic and acquired resistances to antibiotics. In the past, the majority of infections were caused by Enterococcus faecalis; however, an increase in Enterococcus faecium clinical isolates has been observed in recent years. The enterococcal surface protein (Esp) is expressed on the surface of most E. faecium clinical isolates and has been shown to be involved in biofilm formation. Here, E. faecium E1162 and its previously created insertion-deletion mutant of the esp gene, E. faecium E1162Deltaesp, were compared in a mouse bacteraemia model. Anti-Esp serum was tested for its capacity to mediate opsonophagocytic killing of E1162 in vitro and to protect against E. faecium bacteraemia. The inactivation of esp attenuated E. faecium virulence with reduced numbers of bacteria recovered from the kidneys in animals infected with the mutant compared to the wild-type strain (P=0.035). Passive immunization with rabbit polyclonal serum raised against the recombinant N-terminal Esp protein did not protect mice against E. faecium bacteraemia (P>0.05). In contrast, mice passively immunized with polyclonal antiserum raised against lipoteichoic acid (LTA) from E. faecalis had lower numbers of E. faecium E1162 in the blood compared to mice immunized with normal rabbit serum. These results suggest that Esp contributes to E. faecium persistence in the host. However, in contrast to LTA, Esp does not seem to be a target for protective antibodies in E. faecium strain E1162 in mouse bacteraemia.

Outcomes of invasive infection due to vancomycin-resistant Enterococcus faecium during a recent outbreak.

BACKGROUND: Earlier reports have shown a high mortality of invasive infection due to vancomycin-resistant Enterococcus faecium (VREF). Most of these studies have been conducted in US hospitals prior to the advent of newer VREF-active antimicrobials, and the reported poor outcomes have been explained by the limited choices for effective antimicrobial therapy. PATIENTS AND METHODS: A total of 25 cases of invasive VREF infection were seen during an outbreak in a tertiary care hospital. Patient characteristics and outcomes were evaluated by a structured retrospective chart review and descriptive analysis. RESULTS: Severe underlying diseases such as leukemia not in remission (86%) were highly prevalent among patients with invasive VREF infection. Fifty-two percent of underlying diseases and/or comorbidities were considered according to the McCabe classification as rapidly fatal. Most patients had received high-dose cytotoxic chemotherapy, and many were neutropenic at the onset of VREF infection. Concomitant infection due to other organisms was found in 48% of the patients. All patients had received extensive antibiotic treatment prior to the onset of VREF infection. Resistance to linezolid was observed in four cases. Overall survival at day 30 was 48%. Four deaths were considered to be directly related to VREF infection. CONCLUSION: Invasive VREF infection during this outbreak was confined to patients with severe underlying comorbidity. The mortality of VREF infection remained high, despite treatment with newer VREF-active antibiotics such as linezolid and quinupristin-dalfopristin.

[Prevention of infections and thromboses after splenectomy or because of functional loss of the spleen]. / Prävention von Infektionen und Thrombosen nach Splenektomie oder bei Funktionsverlust der Milz.

Overwhelming Post-Splenectomy Infection (OPSI or PSS), most frequently caused by encapsulated Gram-positive pathogens, is a complication after splenectomy. Reasons for splenectomy include trauma, or malignant and non-malignant hematologic diseases. OPSI-inducing bacteria are mainly Streptococcus pneumoniae and less frequently Haemophilus influenzae, Neisseria meningitides and Gram-negative bacilli. There exist very efficient--albeit often neglected--strategies, how to prevent infections in patients after splenectomy. These include vaccination, prophylactic antibiotics (always for 3 years during childhood and adolescence) and prompt antibiotic treatment, if an infection is suspected. Patients need to know the nature and likelihood of PSS and they should seek immediate medical attention if they become ill or febrile. Each patient should carry at all times a letter or card documenting the splenectomy. With these measures and precautions, the PSS-risk can be significantly reduced or at best be completely avoided.

[Ulcerous colitis and infection with cytomegalovirus, herpes simplex virus and clostridium difficile]. / Schwere Colitis ulcerosa und Infektion mit Cytomegalieviren, Herpes-simplex-Viren und Clostridium difficile.

The treatment of severe flares of ulcerative colitis is based on systemic corticosteroids, immunomodulators such as cyclosporine and azathioprine and in some cases TNF-alpha-antagonists, respectively. These immunosuppressed patients are susceptible for infectious pathogens. Here we report the case of a patient with a severe flare of ulcerative colitis that was first treated with systemic corticosteroids combined with immunomodulators and subsequent with infliximab. The patient then experienced an infection with Clostridium difficile and cytomegalovirus of the colon and a Herpes simplex esophagitis, respectively. After specific treatment the patient responded well to the immunosuppressive therapy. This case illustrates that infections have to be considered before systemic treatment of an acute flare of ulcerative colitis is instituted especially in the case of disease activation during immunosuppressive treatment.

Lymphocyte subsets in peripheral blood and smoking habits.

The investigation of peripheral blood lymphocyte (PBL) subpopulations is of interest in a wide variety of inflammatory diseases. Since the number of circulating lymphocytes has been shown to be affected by smoking habits, it seems useful to know how PBL subpopulations are influenced. We therefore determined percentages and absolute numbers of a wide range of PBL subpopulations in smokers (n = 14) and nonsmokers (n = 14). PBLs were obtained from healthy volunteers and analyzed by flow cytometry using antibodies for the detection of CD3, CD4, CD8, CD19, CD56, CD57, CD45RO, CD45RA, alpha/beta and gamma/delta T cell receptor epitopes. With the exception of CD3+ cells, no differences between smokers and nonsmokers were found regarding percentages of PBL subpopulations. Smokers were found to have higher absolute numbers of PBLs in the following subpopulations compared with nonsmokers: CD3+, CD4+, CD3+ alpha/beta +, CD45RO+/CD4+, and CD45RA+/CD4+. Cytotoxic lymphocytes, natural killer cells, and B cells did not differ in number between smokers and nonsmokers. There was likewise no difference in the number of the CD8+ alpha/beta + and all cells bearing the gamma/delta T cell receptor. Smoking increased the number of T cells and mainly CD4+ PBLs. The smoking habits of healthy control groups should therefore be taken into account when comparing lymphocyte subpopulations in different diseases.