Invasive disease by Haemophilus influenzae in Sweden in the era of the H. influenzae type b vaccine

What is the current status of Haemophilus influenzae as an agent of invasive infection in Sweden? H. influenzae type b (Hib) used to be a common cause of meningitis, epiglottitis and severe sepsis in young children. In the late 1980’s an effective conjugated vaccine against Hib was developed and a dramatic fall in Hib incidence was observed in countries that implemented vaccination. This includes Sweden, where the vaccine was implemented in 1992. Since the mid 1990’s, scattered international reports have suggested increasing incidences of invasive disease caused by non-type b isolates of H. influenzae. A few of these reports have suggested serotype replacement. In order to answer the initial question, we studied the epidemiology, the clinical burden and antimicrobial resistance of invasive H. influenzae in Sweden 1997-2010. Two aspects of the pathogenesis of invasive H. influenzae disease were addressed; bacterial binding to the extracellular matrix and the role of complement regulator binding in invasive disease. A case report of a severe invasive H. influenzae type f infection, including an examination of contributing host factors, is also presented. Our results suggest that invasive disease by H. influenzae has not disappeared, but the epidemiology has radically changed. We found no support for serotype replacement in young children. In adults, and especially elderly adults, the incidence of invasive disease by non-typeable H. influenzae (NTHi) increased significantly during the study period. The results also suggest an increased incidence of invasive disease by H. influenzae type f (Hif), and type f is the most common serotype in Sweden today. Cases of invasive disease by non-type b isolates that occurred in healthy adults were often severe, suggesting the existence of hypervirulent non-type b strains. The β-lactam resistance of invasive H. influenzae isolates increased during the study period, due to an increase of β-lactamase negative β-lactam resistant NTHi. A clonal expansion of a β-lactamase negative ampicillin resistant (BLNAR) clone, frequently found in invasive disease, was suggested. The ability of H. influenzae to bind laminin, and anchor the extracellular matrix through the adhesin Protein E was confirmed. Binding to complement regulators was not higher in invasive as compared to nasopharyngeal NTHi isolates, and thus did not seem central for invasive capacity. Speculation, but no comprehensive conclusion as to what host factors relate to invasive disease by H. influenzae in adults was possible. The results suggest that the vaccination against H. influenzae type b remains very effective 20 years after it was introduced, but that continued surveillance of incidence and antimicrobial resistance of invasive Haemophilus disease is warranted. The results also suggest that ongoing research should focus on non-typeable H. influenzae, which today dominates all types of H. influenzae infections

Increase of beta-Lactam-Resistant Invasive Haemophilus influenzae in Sweden, 1997 to 2010

The proportions of Haemophilus influenzae resistant to ampicillin and other beta-lactam antibiotics have been low in Sweden compared to other countries in the Western world. However, a near-doubled proportion of nasopharyngeal Swedish H. influenzae isolates with resistance to beta-lactams has been observed in the last decade. In the present study, the epidemiology and mechanisms of antimicrobial resistance of H. influenzae isolates from blood and cerebrospinal fluid in southern Sweden from 1997 to 2010 (n = 465) were studied. Antimicrobial susceptibility testing was performed using disk diffusion, and isolates with resistance to any tested beta-lactam were further analyzed in detail. We identified a significantly increased (P = 0.03) proportion of beta-lactam-resistant invasive H. influenzae during the study period, which was mainly attributed to a significant recent increase of beta-lactamase-negative beta-lactam-resistant isolates (P = 0.04). Furthermore, invasive beta-lactamase-negative beta-lactam-resistant H. influenzae isolates from 2007 and onwards were found in higher proportions than the corresponding proportions of nasopharyngeal isolates in a national survey. Multiple-locus sequence typing (MIST) of this group of isolates did not completely separate isolates with different resistance phenotypes. However, one cluster of beta-lactamase-negative ampicillin-resistant (BLNAR) isolates was identified, and it included isolates from all geographical areas. A truncated variant of a beta-lactamase gene with a promoter deletion, bla(TEM-1)-P Delta dominated among the beta-lactamase-positive H. influenzae isolates. Our results show that the proportions of beta-lactam-resistant invasive H. influenzae have increased in Sweden in the last decade

Antimicrobial stewardship programs; a two-part narrative review of step-wise design and issues of controversy Part I : step-wise design of an antimicrobial stewardship program

Regardless of one’s opinion of antimicrobial stewardship programs (ASPs), it is hardly possible to work in hospital care and not be exposed to the term or its practical effects. Despite the term being relatively new, the number of publications in the field is vast, including several excellent reviews of general and specific aspects. Work in antimicrobial stewardship is complex, and includes not only aspects of infectious disease and microbiology, but also of epidemiology, genetics, behavioural psychology, systems science, economics and ethics, to name a few. This review aims to take several of these aspects and the scientific evidence of antimicrobial stewardship studies and merge them into two questions: How should we design ASPs based on what we know today? And which are the most essential unanswered questions regarding antimicrobial stewardship on a broader scale? This narrative review is written in two separate parts aiming to provide answers to the two questions. This first part is written as a step-wise approach to designing a stewardship intervention based on the pillars of unmet need, feasibility, scientific evidence and necessary core elements. It is written mainly as a guide to someone new to the field. It is sorted into five distinct steps: (a) focusing on designing aims; (b) assessing performance and local barriers to rational antimicrobial use; (c) deciding on intervention technique; (d) practical, tailored design including core element inclusion; and (e) evaluation and sustainability. The second part, published separately, formulates ten critical questions on controversies in the field of antimicrobial stewardship. It is aimed at clinicians and researchers with stewardship experience and strives to promote discussion, not to provide answers

Antimicrobial stewardship programs; a two-part narrative review of step-wise design and issues of controversy. Part II: Ten questions reflecting knowledge gaps and issues of controversy in the field of antimicrobial stewardship

Regardless of one’s opinion on antimicrobial stewardship programs (ASPs), it is hardly possible to work in hospital care and not be exposed to the term or its practical effects. Despite the term being relatively new, the number of publications in the field is vast, including several excellent reviews of general and specific aspects. Work in antimicrobial stewardship is complex, and include aspects not only of infectious disease and microbiology, but also of epidemiology, genetics, behavioural psychology, systems science, economics and ethics, to name but a few. This review aims to take several of these aspects and the scientific evidence from antimicrobial stewardship studies and merge them into two questions: How should we design ASPs based on what we know today? and Which are the most essential unanswered questions regarding antimicrobial stewardship on a broader scale? This narrative review is written in two separate parts aiming to provide answers to the two questions. The first part, published separately, is written as a step-wise approach to designing a stewardship intervention based on the pillars of unmet need, feasibility, scientific evidence and necessary core elements. It is written mainly as a guide to someone new to the field. It is sorted into five distinct steps; (a) focusing on designing aims; (b) assessing performance and local barriers to rational antimicrobial use; (c) deciding on intervention technique; (d) practical, tailored design including core element inclusion; and (e) evaluation and sustainability. This second part formulates 10 critical questions on controversies in the field of antimicrobial stewardship. It is aimed at clinicians and researchers with stewardship experience and strives to promote discussion, not to provide answers

Antimicrobial Stewardship : What We All Just Need to Know

Antimicrobial stewardship programmes including a multidisciplinary team of urologists, infectious disease specialists, and microbiologists reduce the total use of antibiotics in urological care without jeopardising the patient outcome. It is a recommended tool for education and feedback

The prevalence of ESBL-producing Enterobacteriaceae in a nursing home setting compared with elderly living at home: a cross-sectional comparison.

The aim of the study was to investigate the prevalence of faecal carriage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae among residents living in nursing homes and to compare it with a corresponding group of elderly people living in their own homes

Benzylpenicillin versus wide-spectrum beta-lactam antibiotics as empirical treatment of Haemophilus influenzae-associated lower respiratory tract infections in adults; a retrospective propensity score-matched study

There is consensus that definitive therapy for infections with H. influenzae should include antimicrobial agents with clinical breakpoints against the bacterium. In Scandinavia, benzylpenicillin is the recommended empirical treatment for community-acquired pneumonia (CAP) except in very severe cases. However, the effect of benzylpenicillin on H. influenzae infections has been debated. The aim of this study was to compare the outcomes of patients given benzylpenicillin with patients given wide-spectrum beta-lactams (WSBL) as empirical treatment of lower respiratory tract H. influenzae infections requiring hospital care. We identified 481 adults hospitalized with lower respiratory tract infection by H. influenzae, bacteremic and non-bacteremic. Overall, 30-day mortality was 9% (42/481). Thirty-day mortality, 30-day readmission rates, and early clinical response rates were compared in patients receiving benzylpenicillin (n = 199) and a WSBL (n = 213) as empirical monotherapy. After adjusting for potential confounders, empirical benzylpenicillin treatment was not associated with higher 30-day mortality neither in a multivariate logistic regression (aOR 2.03 for WSBL compared to benzylpenicillin, 95% CI 0.91–4.50, p = 0.082), nor in a propensity score-matched analysis (aOR 2.14, 95% CI 0.93–4.92, p = 0.075). Readmission rates did not significantly differ between the study groups, but early clinical response rates were significantly higher in the WSBL group (aOR 2.28, 95% CI 1.21–4.31, p = 0.011), albeit still high in both groups (84 vs 81%). In conclusion, despite early clinical response rates being slightly lower for benzylpenicillin compared to WSBL, we found no support for increased mortality or readmission rates in patients empirically treated with benzylpenicillin for lower respiratory tract infections by H. influenzae

The usefulness of appetite and energy intake-based algorithms to assess treatment effect of a bacterial infection : An observational prospective study

Background: The diagnosis of infectious diseases and the duration of antibiotic therapies are generally based on empirical rules. Studies implicate that the use biological markers can be used as a reliable method to shorten antibiotic therapies. The return of appetite is a clinical aspect of recovery from an infection that may be used to guide antibiotic therapies. Objective: To compare changes in appetite and daily energy intake with changes in CRP-levels in patients recovering from an infection. Design: Observational study using a consecutive sample of patients admitted to the unit for infectious diseases at a University Hospital in Sweden, February to April 2014. Energy intake, CRP-levels and appetite were recorded daily. Energy intake was calculated using estimated energy contents. Appetite was measured using a validated visual analogue scale. Changes in daily energy intakes, CRP-levels and appetite were analysed. Results: 49 patients (51% men) were included in the analysis from the overall population of 256 patients. During the length of the stay (median 3 days) CRP-levels fell in 92% of the patients (p<0.001), daily energy intake increased in 73% (median intake +6381 kJ/day, p<0.001) and appetite increased in 55% of the patients (p = 0.181). VAS-estimations of appetite augmented in 55%, decreased in 41% and were equal in 5% of the patients (p = 0.181). There was a non-significant difference in the within-subject variances in daily energy intake between female and male patients but not in other subsets. Conclusions: We found a significantly increase in the daily energy intake but not in self-estimated appetite in patients recovering from an infection. We suggest measuring the daily energy intake as a complement to other biological and clinical markers among inpatients to assess treatment effect