Adult vaccination for pneumococcal disease: a comparison of the national guidelines in Europe.

Pneumococcal disease constitutes a major global health problem. Adults aged over 50 years and younger adults with specific chronic health conditions are at risk for invasive pneumococcal disease, associated with substantial morbidity and mortality. In Europe, two vaccine types are used in adults for pneumococcal immunization: pneumococcal polysaccharide vaccine (PPV23) and pneumococcal conjugate vaccine (PCV13). To provide an overview and to compare the national guidelines for pneumococcal immunization for adults in Europe. In November 2016, national guidelines on pneumococcal vaccination for adults of 31 European countries were obtained by Google search, the website of European Centre for Disease Prevention and Control, and contacting public health officials. In our analysis, we distinguished between age-based and risk-based guidelines. In October 2017, we used the same method to retrieve guideline updates. We observed great variability regarding age, risk groups, vaccine type, and use of boosters. In age-based guidelines, vaccination is mostly recommended in adults aged over 65 years using PPV23. Boosters are generally not recommended. An upper age limit for vaccination is reported in three countries. In the immunocompromised population, vaccination with both vaccines and administration of a booster is mostly recommended. In the population with chronic health conditions, there is more heterogeneity according vaccine type, sequence, and administration of boosters. Asplenia is the only comorbidity for which all countries recommend vaccination. The great variability in European pneumococcal vaccination guidelines warrants European unification of the guidelines for better control of pneumococcal disease.

Prevalence and distribution of beta-lactamase coding genes in third-generation cephalosporin-resistant Enterobacteriaceae from bloodstream infections in Cambodia.

Resistance to third-generation cephalosporins in Gram-negative bacteria is emerging in Asia. We report the prevalence and distribution of extended-spectrum beta-lactamase (ESBL), AmpC beta-lactamase and carbapenemase-coding genes in cefotaxime-resistant Enterobacteriaceae isolates from bloodstream infections (BSI) in Cambodia. All Enterobacteriaceae isolated from BSI in adult patients at Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia (2007-2010) were assessed. Antimicrobial susceptibility testing was carried out by disc diffusion and MicroScan according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Screening for ESBL, plasmidic AmpC and carbapenemase-coding genes was performed by multiplex polymerase chain reaction (PCR) sequencing assays. Identification of the ST131 clone was performed in all CTX-M-positive Escherichia coli, using PCR targeting the papB gene. Out of 183 Enterobacteriaceae, 91 (49.7 %) isolates (84 BSI episodes) were cefotaxime-resistant: E. coli (n = 68), Klebsiella pneumoniae (n = 17) and Enterobacter spp. (n = 6). Most episodes were community-acquired (66/84; 78.3 %). ESBLs were present in 89/91 (97.8 %) cefotaxime-resistant isolates: 86 (96.6 %) were CTX-M, mainly CTX-M-15 (n = 41) and CTX-M-14 (n = 21). CTX-M of group 1 were frequently associated with TEM and/or OXA-1/30 coding genes and with phenotypic combined resistance to ciprofloxacin, sulphamethoxazole-trimethoprim and gentamicin (39/50, 78.0 %). Plasmidic AmpC (CMY-2 and DHA-1 types) were found alone (n = 2) or in combination with ESBL (n = 4). Eighteen E. coli isolates were identified as B2-ST131-O25B: 11 (61.1 %) carried CTX-M-14. No carbapenemase-coding genes were detected. ESBL among Enterobacteriaceae from BSI in Cambodia is common, mainly associated with CTX-M-15 and CTX-M-14. These findings warrant urgent action for the containment of antibiotic resistance in Cambodia.

The aetiology and antibiotic management of community-acquired pneumonia in adults in Europe: a literature review.

The purpose of this paper was to generate up-to-date information on the aetiology of community-acquired pneumonia (CAP) and its antibiotic management in adults across Europe. Structured searches of PubMed identified information on the aetiology of CAP and its antibiotic management in individuals aged >15 years across Europe. We summarise the data from 33 studies published between January 2005 and July 2012 that reported on the pathogens identified in patients with CAP and antibiotic treatment in patients with CAP. Streptococcus pneumoniae was the most commonly isolated pathogen in patients with CAP and was identified in 12.0-85.0 % of patients. Other frequently identified pathogens found to cause CAP were Haemophilus influenzae, Gram-negative enteric bacilli, respiratory viruses and Mycoplasma pneumoniae. We found several age-related trends: S. pneumoniae, H. influenzae and respiratory viruses were more frequent in elderly patients aged ≥65 years, whereas M. pneumoniae was more frequent in those aged <65 years. Antibiotic monotherapy was more frequent than combination therapy, and beta-lactams were the most commonly prescribed antibiotics. Hospitalised patients were more likely than outpatients to receive combination antibiotic therapy. Limited data on antibiotic resistance were available in the studies. Penicillin resistance of S. pneumoniae was reported in 8.4-20.7 % of isolates and erythromycin resistance was reported in 14.7-17.1 % of isolates. Understanding the aetiology of CAP and the changing pattern of antibiotic resistance in Europe, together with an increased awareness of the risk factors for CAP, will help clinicians to identify those patients most at risk of developing CAP and provide guidance on the most appropriate treatment.

Epidemiology and outcome of invasive pneumococcal disease among adults in Belgium, 2009-2011.

This epidemiological study examined morbidity and case fatality of invasive pneumococcal disease (IPD) in adults in Belgium as well as distribution and antibiotic susceptibility of Streptococcus pneumoniae serotypes.Adults hospitalised with microbiologically proven IPD were prospectively enrolled. The study started in 2009 with patients aged ≥50 years, whereas in 2010 and 2011, patients aged ≥18 years were included. The clinical presentation, patient profile, treatment, outcome, and mortality were recorded during hospitalisation.Outcome was also assessed one month afterdischarge. Of the 1,875 patients with IPD identified, 1,332 were included in the analysis. Bacteraemic pneumonia, affecting 1,049 of the patients, was the most frequent IPD type (79%), and chronic obstructive pulmonary disease and cancer were the main comorbidities.One-third of patients required admission to intensive care unit. A total of 208 (16%) patients died during hospitalisation and an additional 21 (2%) within one month after discharge. Case fatality rates of ≥20%were observed in patients with chronic heart failure, hepatic disease, and renal insufficiency. Serotypes 7F, 1, 19A, and 3 were the most prevalent and together accounted for 47% (569/1,214) of all IPD cases and 42% (80/189) of mortality. Of the patient isolates, 21% (255/1,204) were resistant to erythromycin and 22% (264/1,204) to tetracycline. Penicillin non-susceptibility was mostly found in serotype 19A isolates. These baseline data are essential when assessing the impact of pneumococcal conjugate vaccination in adults in the future.

Comparing normal saline versus diluted heparin to lock non-valved totally implantable venous access devices in cancer patients: a randomised, non-inferiority, open trial.

BACKGROUND: Heparin has been used for years as a locking solution in totally implantable venous access devices. Normal saline (NS) might be a safe alternative for heparin. However, evidence of non-inferiority of NS versus heparin is lacking. PATIENTS AND METHODS: We randomly allocated 802 cancer patients with a newly inserted port either to heparin lock (300 U/3 ml) or to NS lock groups in a 1:1 assignment ratio. The primary outcome was the number of functional complications, which was defined as 'easy injection, impossible aspiration' at port access. Secondary outcomes included all functional problems and catheter-related bacteraemia. We hypothesised that NS locks do not cause more functional problems and catheter-related bacteraemia than heparin locks. Non-inferiority is established if the upper limit of the confidence interval (CI) for the relative risk of NS versus heparin is <1.4. RESULTS: Three hundred and eighty-two patients from the NS group and 383 from the heparin lock group were included in the analysis. The incidence rate of our primary outcome (easy injection, impossible aspiration) was 3.70% (95% CI 2.91%-4.69%) and 3.92% (95% CI 3.09%-4.96%) of accesses in the NS and heparin groups, respectively. The relative risk was 0.94% (95% CI 0.67%-1.32%). Catheter-related bloodstream infection was 0.03 per 1000 catheter days in the NS group and 0.10 per 1000 catheter days in the heparin group. CONCLUSION: NS is a safe and effective locking solution in implantable ports if combined with a strict protocol for device insertion and maintenance.

Dengue: current state one year before WHO 2010-2020 goals.

BACKGROUND: Dengue is a possibly life-threatening human mosquito-borne viral infection widely spread in peridomestic (sub)tropical climates. The global incidence has expanded rapidly in the last decades, with 40% of the world's population currently at risk. To date, no anti-viral treatment other than supportive care exists. In 2015, the first and only dengue-vaccine, CYD-TDV, received marketing authorization. OBJECTIVES: To present the current understanding of dengue in terms of epidemiology, transmission, pathogenesis, disease management and prevention. To illustrate the knowledge gaps that remain to be filled in order to control dengue and achieve the WHO 2010-2020 goals. METHODS: An updated systematic review (2009-2019) was carried out. The databases Pubmed, Embase and The Cochrane Library were searched along with WHO and CDC guidelines. RESULTS: In total, 39 articles were included. Contemporary climatic and economic factors significantly contributed to the emergence of epidemic dengue. Unfortunately, CYD-TDV failed to meet safety and efficacy demands. New vaccination approaches are in the pipeline along with innovative vector-control strategies. Current anti-viral drug research focuses on repurposing drugs in addition to specific anti-dengue strategies that interfere with viral replication. CONCLUSION: The lack of understanding dengue pathogenesis and immunology has hampered the development of an effective vaccine. Recent research has provided new insights into the therapeutic and prophylactic approach. Implementation of complementary methods to control disease burden are required considering the socio-economic impact of this rapidly emerging global disease.

Clinical evaluation of the Copan ESwab for methicillin-resistant Staphylococcus aureus detection and culture of wounds.

The screening for and diagnosis of bacteriological infections often involves the collection and transportation of swab samples. The Copan ESwab was compared with the dry cotton Copan swab for methicillin-resistant Staphylococcus aureus (MRSA) screening (n = 200 paired samples) and with the Amies agar gel swab (Copan) for the sampling of burn and orthopaedic wounds (n = 203 paired samples) in terms of Gram staining and bacterial recovery. Gram stains performed with ESwab liquid showed significantly more Gram-negative rods, streptococci, Gram-positive cocci, Gram-positive rods, polymorphonuclear cells, lymphocytes and red blood cells than Gram stains from dry swabs. Bacterial recovery was significantly higher with ESwab (p < 0.01, for both MRSA screening and wounds, quantitative/semi-quantitative method). This lead to a slightly higher detection rate of MRSA (128 vs. 124 MRSA-positive ESwabs and dry swabs, respectively, p = 0.50) and a higher detection rate of coagulase-negative Staphylococcus spp. (44 isolates with ESwab vs. 29 with Amies gel swab, p = 0.001) and Enterococcus spp. (15 isolates with ESwab vs. 7 isolates with Amies gel swab, p = 0.005) with ESwab (quantitative method). We confirmed that ESwab has a high performance for Gram stains and a higher bacterial recovery than dry and Amies gel swabs when using clinical samples for MRSA screening and wound sampling.

Treatment of mycotic aneurysms with involvement of the abdominal aorta: single-centre experience in 44 consecutive cases.

OBJECTIVE: To review our management of mycotic aneurysms involving the abdominal aorta over the past 2 decades to assess the safety and efficacy of in-situ and extra-anatomic repair combined with antibiotic treatment. MATERIALS AND METHODS: From March 1990 to August 2008, 44 patients with a mycotic aneurysm involving the abdominal aorta were treated at our University Hospital. For all patients, we recorded the aetiology, clinical findings and anatomic location of the aneurysm, as well as bacteriology results, surgical and antibiotic therapy and morbidity and mortality. RESULTS: Twenty-one (47.7%) of the mycotic aneurysms had already ruptured at the time of surgery. Free rupture was present in nine patients (20.5%). Contained rupture was observed in 12 patients (27.3%). Urgent surgery was performed in 18 cases (40.9%). Revascularisation was achieved by in-situ reconstruction in 37 patients (84.1%), while extra-anatomic reconstruction was performed in six patients (13.6%). One patient (2.3%) was treated with a combined in-situ and extra-anatomic reconstruction. In one case (2.3%), endovascular aneurysm repair (EVAR) was performed. In-hospital mortality was 22.7%, 50% in the extra-anatomic reconstruction group and 18.9% in the in-situ repair group. One-third (33.3%) of our patients, who presented with a ruptured mycotic aneurysm died in the peri-operative period. This mortality was 13% in the patient-group presenting with an intact aneurysm. Of the 34 surviving patients, 12 patients (27.3% of surviving patients died after discharge from our hospital. In half of these patients, an acute cardiac event was to blame. Three patients (8%) showed re-infection after in-situ reconstruction. CONCLUSION: Management of mycotic aortic aneurysms remains a challenging problem. The results of surgery depend on many factors. In our experience, in-situ repair remains a feasible and safe treatment option for patients who are in good general condition at the time of surgery.

Aggressive cutaneous squamous cell carcinoma associated with prolonged voriconazole therapy in a renal transplant patient.

A 69-year-old man, with a history of end-stage renal disease due to polyarteritis nodosa, followed by invasive pulmonary aspergillosis secondary to cyclophosphamide and corticosteroids, received a renal transplant 2 years ago under prophylactic treatment with voriconazole. Because of the severity of the aspergillosis, it was decided to continue voriconazole for a prolonged period. Eighteen months after transplantation, the patient developed a severe facial phototoxic reaction. A few months later, he developed multiple actinic keratoses and a large, rapidly expanding, poorly differentiated squamous cell carcinoma (SCC) with perineural invasion and metastatic lymph nodes, necessitating radical surgery and radiotherapy. Voriconazole therapy has been suggested to be involved in the development of multi-focal invasive SCC when complicated by a phototoxic reaction. Therefore, an alternative antifungal prophylaxis regimen (for instance with posaconazole) should be considered when evaluating patients for solid organ transplantation who are at high risk for the development of cutaneous malignancies.

Influenza vaccination is efficacious and safe in renal transplant recipients.

Whether influenza vaccination in solid-organ transplant recipients is efficacious remains a controversial issue. Furthermore, theoretical concerns have been raised regarding the safety of vaccination as it might trigger rejection of the allograft. The present prospective trial is aimed at investigating the antibody response and safety of influenza vaccination in renal transplant recipients (RTR). A total of 165 RTR and 41 healthy volunteers were vaccinated with a standard trivalent inactivated influenza vaccine. Hemagglutination-inhibiting (HI) antibodies were quantified before and 1 month after vaccination. Seroprotection (SP) and seroresponse (SR) were defined as a titer > or =40 and a 4-fold rise in HI titer, respectively. Similar SR rates were observed in both groups. Postvaccination SP rates in RTR amounted to 92.7%, 78.7% and 82.9% for A/H1N1, A/H3N2 and B, respectively. High baseline SP rates, most probably reflecting frequent preimmunizations, explain partly the high postvaccination SP rates. SR rate was independently and inversely associated with baseline SP rate. Mycophenolate mofetil (MMF) usage was associated with a 2.6-5-fold lower SR. Nonetheless, these patients showed good postvaccination SP rates. A booster dose did not enhance SP or SR rates. Influenza vaccination neither affected allograft function nor caused rejection episodes. In conclusion, influenza vaccination is efficacious and safe in renal transplantation.

Added diagnostic value and impact on antimicrobial therapy of 16S rRNA PCR and amplicon sequencing on resected heart valves in infective endocarditis: a prospective cohort study.

OBJECTIVES: For adequate management and therapy of infective endocarditis (IE), identification of the causative pathogen is crucial but molecular testing results are not currently included in diagnostic criteria. The added diagnostic value and impact on antimicrobial therapy of 16S rRNA PCR and amplicon sequencing (16S rRNA PCR) performed on excised heart valves from patients with IE was evaluated alongside the effect of pre-operative antibiotics on the performance of blood culture (BC), valve culture (VC) and 16S rRNA PCR. METHODS: All patients undergoing valve surgery for definite or possible IE, according to modified Duke Criteria, were prospectively included from July 2013 up to and including June 2016. RESULTS: In all, 127 patients were included. Sensitivity for detecting the causative micro-organism in 120 post-operative definite IE patients was 26% for VC and 87% for BC and 16S rRNA PCR. 16S rRNA PCR, VC and BC were equally sensitive for different valve types and causative pathogens. In 27 (21%) definite IE patients, 16S rRNA PCR clarified discrepant culture results or was the only method identifying the causative pathogen. In 12 (10%) post-operative definite IE cases, molecular testing results influenced antimicrobial therapy. CONCLUSIONS: The very good performance characteristics, added diagnostic value and impact on antimicrobial therapy of molecular testing of heart valves should support the incorporation of molecular testing in diagnostic criteria and guidelines for IE.

Evolving trends in infective endocarditis.

Infective endocarditis is a microbial infection of the endocardial surface and, despite improvements in diagnostic accuracy, medical therapy and surgical techniques, mortality remains high. This review focuses on changes in epidemiology, microbiology and diagnosis, as well as changes in medical and surgical management of infective endocarditis affecting native and prosthetic valves in adults, that have evolved during the past two decades. Significant changes have included an increasing involvement of prosthetic valves and nosocomially-acquired disease, an increased involvement of staphylococci as the causative agents, and a recognition that elderly individuals with degenerative valvular disease are the most vulnerable population. Topics still requiring study include whether and when valve replacement should be performed, and how to predict perivalvular complications or embolisation based on echocardiography findings. Optimisation of antimicrobial treatment schemes (choice of the antibiotic, dose and duration) also requires further investigation.

Treating respiratory tract infections in ambulatory care in Belgium: fluoroquinolone consumption and resistance development.

This study analyses consumption patterns of fluoroquinolones in treating respiratory tract infections in ambulatory care in Belgium and describes susceptibility of Streptococcus pneumoniae isolates to fluoroquinolones. Consumption data were obtained from IMS Health. Pneumococcal resistance was investigated in 600 blood isolates collected from 1998 to 2003. Although consumption of fluoroquinolones has increased rapidly over the last decade, this trend does not seem to persist more recently. Fluoroquinolones were mainly used to treat urinary and lower respiratory tract infections, but rarely in the management of upper respiratory tract infections. The use of new fluoroquinolones (levofloxacin, moxifloxacin) and the ongoing use of older fluoroquinolones have not led to increased pneumococcal resistance, which remained below 1% for levofloxacin and was 0% for moxifloxacin.

Percutaneous transhepatic cholecystostomy for acute complicated calculous cholecystitis in elderly patients.

OBJECTIVE: To assess the immediate and long-term outcomes of elderly patients with acute complicated cholecystitis treated by percutaneous cholecystostomy. To assess the results of bile cultures obtained in this group of patients. DESIGN: Case series. SETTING: Tertiary care center. PATIENTS: Thirty-two patients, with a mean (+/- S.D.) age of 78 +/- 8 years (range, 58-92 years), and who presented with acute cholecystitis complicated by empyema formation. Sixty-six percent had associated disorders, which rendered them at high risk for surgical intervention. INTERVENTION: Percutaneous transhepatic catheter drainage of the gallbladder, with a mean drainage time of 20 days (range 0-84 days). In addition, endoscopic sphincterotomy with removal of common bile duct stones was performed in six patients and percutaneous aspiration of an associated liver abscess in four cases. RESULTS: Percutaneous cholecystostomy was followed by rapid regression of clinical symptoms and of radiologic abnormalities in all patients. Sixteen cases (50%) underwent elective cholecystectomy 1-12 weeks after cholecystostomy. One of them died of aspiration pneumonia, whereas 15 had no post-operative problems and were discharged 9 days (mean) after surgery. Forty-four percent (14/32) were considered inoperable: they remained completely free of biliary symptoms and died of unrelated illness (22%) after a mean follow-up of 6 months (range, 1-22 months) or are still alive (22%) with a mean follow-up of 15 months (range, 5-36 months). Bile cultures were positive in 75% of the patients. Escherichia coli, other aerobic Gram-negative micro-organisms, and anaerobic bacterial species accounted for 35% (16/46), 28% (13/46), and 20% (9/46) of the isolated bacteria, respectively. All aerobic Gram-negative species tested in vitro were susceptible to gentamicin and to temocillin. CONCLUSIONS: Percutaneous transhepatic cholecystostomy is a safe and effective procedure in the treatment of elderly high-risk patients with acute cholecystitis complicated by empyema formation. It can be followed by elective cholecystectomy, if possible, or by expectant conservative management in patients who are inoperable because of systemic disease.

Reliability of the ica, aap and atlE genes in the discrimination between invasive, colonizing and contaminant Staphylococcus epidermidis isolates in the diagnosis of catheter-related infections.

OBJECTIVES: To evaluate the usefulness of detecting two genes involved in biofilm formation (icaA and aap) and one gene involved in initial adhesion (atlE) for discrimination between contaminant, colonizing and invasive Staphylococcus epidermidis isolates involved in catheter-related infections. PATIENTS: The first group contained 29 isolates that were isolated from the skin of healthy volunteers (contaminant isolates). The second group contained 16 isolates recovered from catheters (>1000 CFUs on quantitative catheter culture) from asymptomatic patients without bacteremia. These isolates were considered to be colonizing isolates. The third group contained 34 isolates grown in >or=2 different blood cultures from patients with a systemic inflammatory response. These isolates were considered to be invasive isolates. RESULTS: The prevalence of atlE did not differ between the three groups. The icaA and aap genes were significantly more prevalent in colonizing isolates (88% aap; 88% icaA) than in invasive isolates (68% aap, P = 0.179; 59% icaA, P = 0.055) and than in skin isolates (52% aap, P = 0.02; 38% icaA, P = 0.002). CONCLUSIONS: The high prevalence of aap and icaA in skin isolates and their higher prevalence in colonizing than in invasive isolates led to a low specificity when these genes were used to differentiate between contamination, colonization and invasive infection. We conclude that, although the prevalence of these genes differs in the three groups, their presence cannot be used for clinical decision-making.

Polyclonal Staphylococcus epidermidis intravascular catheter-related infections.

During a 4-month period we prospectively investigated the frequency of polyclonal catheter infections with Staphylococcus epidermidis. Of each catheter with pure growth of S. epidermidis, six colonies were genotypically analyzed with pulsed-field gel electrophoresis. Two out of 12 patients with catheter infection had a polyclonal infection. Both clones of each catheter had a clearly different antibiotic susceptibility. This study shows that polyclonal catheter infections are not exceptional. Further studies are needed to define the clinical consequences of polyclonal catheter infection.

Rothia dentocariosa, endocarditis and mycotic aneurysms: case report and review of the literature.

Rothia dentocariosa is a rare cause of endocarditis. It occurs most frequently in patients with prior heart conditions. Although the clinical course is typically subacute, it has a high rate of complications. In particular, the reported incidence of mycotic aneurysms is as high as 25%. Penicillin is the treatment of choice, but additional complications may necessitate prompt surgical intervention. As far as we know, this paper reports the first case of repeated subarachnoid hemorrhages due to R. dentocariosa endocarditis.

The role of glycopeptide antibiotics in the treatment of infective endocarditis.

There are several sets of guidelines for the treatment of infective endocarditis, reflecting the need for differing treatment in various countries and times. This review considers the need for differing treatment modalities and in particular the utility of the glycopeptide antibiotics vancomycin and teicoplanin. Specific recommendations are offered as to when to consider the use of glycopeptides, appropriate dosage, length of treatment course and whether to use monotherapy or combined therapy. Used judiciously, the glycopeptides give results as good as can be achieved with other antimicrobial agents without exceptional toxicity. The potential of teicoplanin for use in the outpatient treatment of infective endocarditis is considered.

Origin and transmission of methicillin-resistant Staphylococcus aureus in an endemic situation: differences between geriatric and intensive-care patients.

Imported vs. hospital-acquisition of MRSA was assessed in > 6000 patients at a large tertiary care teaching hospital. About five percent (5.1%) of patients carried MRSA on admission, mostly without clinical symptoms; the highest percentage (11.6%) being in geriatric patients. Hospital-acquisition of MRSA occurred in 1.7% of patients and was particularly high in intensive-care units (5.2%). Phenotype and genotype analysis of 158 MRSA strains isolated from 61 patients revealed a cluster of closely related strains in the hospital-acquired MRSA infections and the close relationship of this cluster to the regional epidemic MRSA strain. The MRSA strains imported by geriatric patients were genetically different, did not spread between geriatric patients and were only a minor source of nosocomial infection.