European Respiratory Society
Anti-infectives and the Lung

Pulmonary infections are a major cause of morbidity and mortality worldwide. Adequate and timely treatment of these infections is therefore of vital importance, especially when considering the emerging problem of antimicrobial resistance. This Monograph provides a comprehensive up-to-date overview of the use of anti-infectives in lung diseases, with chapters covering community- and hospital-acquired pneumonia, exacerbations of asthma and chronic obstructive pulmonary disease, tuberculosis and nontuberculous mycobacteria pulmonary disease, pleural infections, and fungal diseases. Other chapters address antibiotic stewardship in the community and hospital settings, and the use of antibiotics in specific patient groups (e.g. critically ill and paediatric patients). Mechanisms of action and resistance, diagnostic approaches, therapeutic options (e.g. combination therapy, dosing and routes of administration), and the development of new drugs are also discussed.

  • ERS Monograph
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  4. Page 1
    Abstract
    Matteo Bassetti, Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy. E-mail: mattba@tin.it

    Pulmonary infections represent an important cause of morbidity and mortality, and require prompt antimicrobial treatment. The correct choice of an empirical regimen is paramount in managing LRTIs due to the difficulty in obtaining a microbial diagnosis. Classic antimicrobials used in the treatment of pulmonary infections include β-lactams (with or without β-lactamase inhibitors), macrolides, tetracyclines and fluoroquinolones. Vancomycin and linezolid are the antimicrobials of choice for the treatment of nosocomial pneumonia caused by MRSA. New compounds have been studied to target pulmonary infections, including those caused by pathogens that are resistant to commonly used antimicrobials. A broad spectrum of activity, penetration into lung tissue, good tolerability, and availability of both oral and intravenous formulations represent key features of the compounds used in the treatment of LRTIs. In this chapter, we summarise the characteristics of commonly used molecules for the treatment of pulmonary infections in adult patients and discuss new options for their treatment.

    Cite as: Bassetti M, Righi E. Antibiotics for pulmonary infections: an overview. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 1–20 [https://doi.org/10.1183/2312508X.10004316].

  5. Page 21
    Abstract
    Oliwia Makarewicz, Center for Infectious Diseases and Infection Control, Jena University Hospital, Am Klinikum 1, 07743 Jena, Germany. E-mail: oliwia.makarewicz@med.uni-jena.de

    Bacterial resistance to antimicrobials is a natural process driven by selective pressure. It is caused by mutational alteration of the genetic information or by incorporation of mobile genetic elements carrying resistance genes. Reduced influx or increased efflux of the antimicrobials often leads to multidrug resistance, whereas mutations in genes encoding antibiotic targets are generally related to resistance to specific antimicrobial classes. In this chapter, we give an overview of the most common resistance mechanisms found in bacterial pathogens of LRTIs.

    Cite as: Makarewicz O, Klinger-Strobel M, Ehricht R, et al. Antibiotic resistance in pulmonary infections: mechanisms and epidemiology. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 21–43 [https://doi.org/10.1183/2312508X.10004416].

  6. Page 44
    Abstract
    Fabio Silvio Taccone, Erasme Hospital, Route de Lennik 808, 1070 Brussels, Belgium. E-mail: Fabio.Taccone@erasme.ulb.ac.be

    Critically ill patients are particularly vulnerable to develop infections and these infections may be caused by pathogens with reduced susceptibility to currently available antibiotics. Rapid, adequate and appropriate individualised antibiotic therapy can help improve outcomes in these patients, and in this chapter we discuss how to optimise this treatment. In order to deliver this kind of therapy, rapid and accurate diagnosis of infection and identification of infecting pathogens and their antibiotic susceptibilities is necessary. This may be facilitated by using new technologies such as MALDI-TOF (matrix-assisted laser desorption ionisation time-of-flight) mass spectrometry and PCR techniques. As the pharmacokinetics of drugs is unpredictable in infected, critically ill patients, routine therapeutic drug monitoring of antibiotics should be considered whenever possible to optimise therapeutic efficacy and reduce risk of toxicity. In order to improve therapeutic efficacy, antibiotics may be given with higher loading doses, in continuous perfusion or by inhalation.

    Cite as: Hites M, Taccone FS. Antibiotics in critical care: dosing, therapeutic drug monitoring and continuous infusions. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 44–56 [https://doi.org/10.1183/2312508X.10004516].

  7. Page 57
    Abstract
    Felix C. Ringshausen, Hannover Medical School, Dept of Respiratory Medicine, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. E-mail: Ringshausen.Felix@mh-hannover.de

    The use of inhaled antibiotics against chronic Pseudomonas aeruginosa infection has been a success story which has significantly contributed to the steadily improving overall survival in patients with cystic fibrosis. Suppressive inhaled antibiotic therapy has been shown to be effective with regard to improvement of clinical symptoms and quality of life. It improves lung function and slows down deterioration of lung function in the long term, while it may also decrease exacerbation frequency and prolong the time to next exacerbation. In contrast, evidence for the clinical benefits in other indications (e.g. bronchiectasis or NTM pulmonary disease), although promising, is still imperfect. Novel data from several clinical trial programmes on inhaled antibiotics in bronchiectasis and refractory NTM pulmonary disease will be available soon, hopefully establishing approved treatment options for these neglected conditions. In this chapter, we summarise the basic concepts, differential indications and future perspectives for the use of inhaled antibiotics in chronic airway infections.

    Cite as: Ringshausen FC, Chalmers JD, Pletz MW. Inhaled antibiotics in chronic airway infections. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 57–79 [https://doi.org/10.1183/2312508X.10004616].

  8. Page 80
    Abstract
    Jean Chastre, Sorbonne Universités, UPMC Université Paris 06, Hôpital Pitié-Salpêtrière, AP-HP, Service de Réanimation Médicale, 47 Boulevard de l'Hopital, 75651 Paris, France. E-mail: jean.chastre@aphp.fr

    Antibiotic aerosolisation in patients with VAP has received renewed interest with the recent development of a new generation of nebulisers that use a vibrating mesh. These devices allow very high concentrations of antimicrobial agents to be achieved in the deep compartment of the lung, well above those achievable using the intravenous route. However, data in critically ill patients with pneumonia are limited; most of the reported experiences are case reports, descriptive studies or literature reviews. According to the systematic reviews and meta-analyses, administration of aerosolised antibiotics might increase the likelihood of clinical resolution (particularly in VAP caused by resistant pathogens), but this is not translated consistently into a significant improvement of important outcomes such as mortality or mechanical ventilation duration. Thus, despite recent promising findings, the widespread use of aerosolised antibiotics to treat pneumonia in the ICU setting cannot be recommended. It should be restricted to the treatment of XDR Gram-negative pneumonia. In these cases, the use of a vibrating-mesh nebuliser seems to be more efficient.

    Cite as: Luyt C-E, Chastre J. Inhaled antibiotics in critical care. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 80–96 [https://doi.org/10.1183/2312508X.10004716].

  9. Page 97
    Abstract
    Stefano Aliberti, Dept of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, Milan 20122, Italy. E-mail: stefano.aliberti@unimi.it

    Among patients with pneumonia coming from the community, it is crucial to identify possible MDR infections at initial diagnosis in order to select the most appropriate empirical treatment and avoid broad-spectrum antibiotic overuse. Healthcare-associated pneumonia (HCAP) criteria currently do not address this issue entirely or correctly. Recent clinical studies show that HCAP criteria do not accurately identify potential MDR organisms, as several additional risk factors associated with MDR infections are now recognised that were not included in the original HCAP definition. Personalised evaluation is therefore necessary in each patient, covering general MDR risk factors and specific risk factors related to MRSA or Pseudomonas aeruginosa. Scoring systems for the stratification of MDR risk could be useful in clinical practice, but they need to be developed based on local epidemiology and specific risk factors.

    Cite as: Di Pasquale M, Aliberti S, Tarsia P, et al. Identifying patients with pneumonia due to MDR organisms coming from the community. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 97–110 [https://doi.org/10.1183/2312508X.10004816].

  10. Page 111
    Abstract
    Daiana Stolz, Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland. E-mail: daiana.stolz@usb.ch

    LRTIs in the outpatient setting are the most common reason for antibiotic prescription worldwide. However, the vast majority of infected patients would recover uneventfully without antimicrobial drugs. The overuse or misuse of antibiotics continues to increase at the same time that the development of novel antimicrobial agents has slowed down. Therefore, there is an urgent need to optimise antibiotic usage in order to improve patient outcomes, decrease adverse consequences (e.g. adverse drug reactions and antimicrobial-associated infections), reduce or prevent antimicrobial resistance and deliver cost-effective therapy. Antimicrobial stewardship has become an important strategy to fight antibiotic misuse and refers to the responsible use of antimicrobials by healthcare professionals and, moreover, to the appropriate selection of antibiotics, duration of treatment, dosage and route of administration for each patient with a suspected infection. In this chapter, we highlight the problems that arise from the overuse and/or misuse of antibiotics, and discuss the principles for antibiotic stewardship for LRTIs in the community.

    Cite as: Papakonstantinou E, Stolz D. Antibiotic stewardship in the community. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 111–126 [https://doi.org/10.1183/2312508X.10004916].

  11. Page 127
    Abstract
    James D. Chalmers, Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital, Dundee, DD1 9SY, UK. E-mail: j.chalmers@dundee.ac.uk

    Antibiotic stewardship is now an international priority in order to conserve the limited pool of available antimicrobial drugs and to reduce the burden of antibiotic-associated complications. As the most common indication for antibiotic prescribing in hospitalised patients, LRTIs are a key target for stewardship interventions. In this chapter, we review the major issues around antibiotic use in hospitals, focusing on the most common indications such as CAP and exacerbations of airways disease. The key principles of antibiotic stewardship are to avoid antibiotic prescription where treatment of bacterial infection is not required, to use the narrowest spectrum required to achieve clinical and microbiological cure, and to limit the duration of treatment where possible. Surveillance data are key to monitoring and implementing stewardship interventions. Accurate data at the local level regarding levels of antimicrobial resistance, antibiotic consumption and adherence to local antibiotic guidelines are required to support stewardship interventions. Current antibiotic use for many respiratory infections is excessive and current guidelines may not appropriately emphasise stewardship principles in many countries. Simple interventions at both the healthcare provider level and individual prescriber level can limit antibiotic resistance and improve patient outcomes.

    Cite as: Chalmers JD, Pletz MW. Antibiotic stewardship in the hospital setting. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 127–149 [https://doi.org/10.1183/2312508X.10017616].

  12. Page 150
    Abstract
    Gernot G.U. Rohde, Dept of Respiratory Medicine, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ Maastricht, The Netherlands. E-mail: g.rohde@mumc.nl

    This chapter covers the difficult topic of antibiotic treatment of exacerbations of asthma and COPD. It gives an overview of the current understanding of the microbiology involved in the two very different diseases and their exacerbations, and introduces the most relevant clinical trials performed so far. The appraisal of the microbiology and the studies will hopefully help clinicians to make educated treatment choices based on the current literature. Moreover, ongoing trials are presented in order to highlight the directions in which the field is evolving.

    Cite as: Rohde GGU. Antibiotics in acute exacerbation of asthma and COPD. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 150–158 [https://doi.org/10.1183/2312508X.10005116].

  13. Page 159
    Abstract
    Sebastian R. Ott, Dept of Pulmonary Medicine, University Hospital (Inselspital) and University of Bern, Freiburgstrasse 4, 3010 Bern, Switzerland. E-mail: sebastianrobert.ott@insel.ch

    The incidence of invasive fungal infection is increasing worldwide, and pulmonary infections in particular have become a major clinical challenge and threat to patients at risk. Most fungal pathogens causing pulmonary infections in humans are ubiquitous in the environment and inhalation is the most common route of acquisition, although pulmonary involvement in disseminated infections originating from other foci may occur. This chapter provides an overview on current diagnostic approaches and therapeutic strategies for the most common pulmonary fungal infections. Effective host defence against pulmonary fungal infections strongly depends on an efficient interaction between different parts of the innate and acquired immunity. Therefore, patients with innate and/or acquired/drug-induced impairment of the immune system and critically ill patients are at highest risk. Furthermore, genetic variations and polymorphisms of genes encoding for different constituents of the immune system seem to increase an individual's susceptibility to fungal infections. The clinical and radiographic appearance of most pulmonary fungal infections is nonspecific. Hence, histological and/or culture proof of fungi from samples taken from affected tissue is required to confirm the diagnosis. Non-culture-based assays and PCR from blood and respiratory samples, particularly BAL fluid, may further facilitate diagnostic efforts and accuracy. Various therapeutic strategies have been implemented for prophylaxis and treatment of pulmonary fungal infections. However, mortality remains considerably high, particularly if initiation of antifungal treatment is delayed. Treatment may be further complicated by inherent and acquired resistance to commonly used antifungals.

    Cite as: Ott SR. Antifungals in pulmonary infections: to whom, when and how? In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 159–184 [https://doi.org/10.1183/2312508X.10005316].

  14. Page 185
    Abstract
    Menno M. van der Eerden, Dept of Respiratory Medicine, Erasmus Medical Centre, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. E-mail: m.vandereerden@erasmusmc.nl

    Antibiotics are typically prescribed as short courses for acute infections, in order to reduce bacterial load, shift the balance in favour of host defences and thus help to overcome infection. Over the past decade, however, interest in the long-term anti-inflammatory and immunomodulatory effects of selected antibiotics has been on the increase. Since the clinical effectiveness of erythromycin was reported in diffuse panbronchiolitis in the 1980s, the use of macrolides has been adopted into many other chronic inflammatory airway diseases characterised by frequent exacerbations, including cystic fibrosis (CF), non-CF bronchiectasis, COPD, severe noneosinophilic asthma, bronchiolitis obliterans after lung transplantation and organising pneumonia. In this chapter, we discuss the indications and limitations of long-term macrolide treatment in these chronic respiratory conditions.

    Cite as: Van Braeckel E, van der Eerden MM. Long-term oral antibiotic treatment: why, what, when and to whom? In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 185–205 [https://doi.org/10.1183/2312508X.10005416].

  15. Page 206
    Abstract
    Yuichiro Shindo, Dept of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: yshindo@med.nagoya-u.ac.jp

    Macrolides, such as azithromycin and clarithromycin, are widely used for the treatment of CAP, and global phase III trials for a novel macrolide, solithromycin, have been completed. Over the past two decades, numerous studies have investigated the effects of macrolides. One of the novel functions of macrolides is their immunomodulatory ability, which suppresses neutrophilic inflammation by decreasing the production of cytokines and other mediators from airway epithelial cells and alveolar macrophages. These immunomodulatory effects may be associated with the effectiveness of macrolides for the treatment of patients with severe CAP. One of the current concerns regarding the adverse effects of macrolides is their cardiovascular toxicity. To avoid macrolide-induced cardiovascular events, physicians should consider the risk factors for QT interval prolongation and cardiac arrhythmias. In this chapter, we summarise the available evidence regarding the beneficial and adverse effects of macrolides, discuss their role in the treatment of pneumonia and highlight the remaining clinical questions to be addressed in future studies.

    Cite as: Shindo Y, Hasegawa Y. Macrolide therapy for patients with pneumonia: a triple-edged sword. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 206–231 [https://doi.org/10.1183/2312508X.10005516].

  16. Page 232
    Abstract
    Giovanni Sotgiu, Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences, University of Sassari, Via Padre Manzella, 4, 07100 Sassari, Italy. E-mail: gsotgiu@uniss.it

    TB is a relevant clinical and public health threat. The annual decline in the incidence rate of TB has been hindered by the emergence and spread of MDR-TB, as well as by TB/HIV co-infection. In 2014, the estimated incidence and mortality of MDR-TB were 480 000 and 190 000, respectively. The highest estimates were provided by China, India and former Soviet Union countries. MDR-TB is the result of human activities, and its proportion is more relevant in previously treated than in new TB cases. However, in several geographical settings, the percentage of MDR-TB among new TB cases is increasing following the transmission of MDR Mycobacterium tuberculosis strains. The current treatment success rate is poor (∼50%), in association with a therapeutic armamentarium that is not highly effective, safe or cheap. New (e.g. bedaquiline, delamanid) and repurposed (e.g. linezolid, clofazimine) drugs are recommended to improve the treatment outcome of difficult-to-treat MDR-TB patients. New therapeutic strategies (e.g. shorter regimens) can achieve better results.

    Cite as: Chang KC, Sotgiu G. Treatment options for MDR- and XDR-TB. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 232–244 [https://doi.org/10.1183/2312508X.10005616].

  17. Page 245
    Abstract
    Nicolas Schönfeld, Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, Walterhöferstrasse 11, 14165 Berlin, Germany. E-mail: nicolas.schoenfeld@helios-kliniken.de

    Antibiotic treatment of pulmonary disease caused by NTM is based on a combination of antimycobacterial drugs. These drugs should be chosen according to the species involved. Evidence from prospective clinical trials is variable. In vitro susceptibility tests have not been validated, but are increasingly being recognised as a plausible potential aid to help combat diseases caused by difficult-to-treat NTM species, particularly in the case of treatment failure. In this chapter, the author seeks to explore areas of controversy and to challenge conventional thinking in the management of NTM pulmonary disease.

    Cite as: Schönfeld N. Perspectives on antibiotic treatment of NTM pulmonary disease. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 245–252 [https://doi.org/10.1183/2312508X.10005716].

  18. Page 253
    Abstract
    Ioannis Psallidas, Oxford University NHS Foundation Trust, Churchill Hospital, Old Road, Oxford, OX3 7LE, UK. E-mail: ioannis.psallidas@ndm.ox.ac.uk

    Pleural infection remains a common and serious respiratory condition with important implications for patients and healthcare services. Diagnosis of the condition can be challenging and its management may require a multidisciplinary approach. Antibiotic therapy, along with pleural drainage, forms the cornerstone of treatment for pleural infection. Culture-positive samples (including both pleural fluid and blood) are found in ∼60% of patients and correct empirical therapy is of paramount importance. Evidence from RCT and case series data have shown that the combination of an intrapleural tissue plasminogen activator and DNase therapy can potentially improve outcomes, but further research is needed to establish the first-line use of such agents. In this chapter, we cover the management of pleural infections, including medical treatment, the role of intrapleural agents and surgical treatment, with a focus on the use of antibiotics.

    Cite as: Bhatnagar R, Skouras VS, Rahman NM, et al. Antibiotics for pleural infections. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 253–263 [https://doi.org/10.1183/2312508X.10005816].

  19. Page 264
    Abstract
    Paolo Spagnolo, Section of Respiratory Diseases, Dept of Cardiac, Thoracic and Vascular Sciences, University of Padua, Via Giustiniani 3, 35128 Padua, Italy. E-mail: paolo.spagnolo@unipd.it

    Interstitial lung diseases (ILDs) represent a large and heterogeneous group of disorders characterised by varying degrees of inflammation and fibrosis. Idiopathic pulmonary fibrosis (IPF), the most common form of ILD, is a relentlessly progressive and invariably fatal disease, which is thought to result from a complex interaction between host/genetic and environmental factors. In IPF, a potential role for infection in disease pathogenesis and progression or as a trigger of disease exacerbation has long been postulated, but studies based on traditional culture methods have yielded inconsistent results. Accordingly, few studies have investigated the efficacy of antibiotics in this setting. The application of new culture-independent techniques for microbiological analysis in IPF has revealed previously unappreciated alterations of the lung microbiome in these patients. The application of these methodologies to larger populations of carefully characterised patients will hopefully clarify the role played by the lung microbiome in IPF, leading to the development of novel treatments for this fatal disease.

    Cite as: Biondini D, Spagnolo P. Antibiotics in interstitial lung diseases. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 264–275 [https://doi.org/10.1183/2312508X.10005916].

  20. Page 276
    Abstract
    Susanna Esposito, Pediatric Clinic, Università degli Studi di Perugia, Piazza Menghini 1, 06129 Perugia, Italy. E-mail: susanna.esposito@unimi.it

    CAP remains a common illness and is a major cause of childhood morbidity worldwide. The use of treatment algorithms in industrialised countries has led to lower mortality rates. However, given the rate of development of antimicrobial resistance, the future of this approach is uncertain. Over the past decade there has been a dramatic increase in the prevalence of antimicrobial resistance in respiratory pathogens, which is related primarily to antimicrobial agents in common use. This observation, in both hospital and community settings, indicates that paediatricians must be made aware of the prevalence of antimicrobial resistance and have a basic understanding of its mechanisms, implementing antimicrobial stewardship programmes to ensure that the most appropriate antimicrobials are selected when initiating therapy. In this chapter, we discuss the aetiology of paediatric CAP as well as its severity, and the diagnostic methods used to identify the optimal first- and second-line antibiotic approaches for children with CAP. We conclude that improvements in diagnosis, treatment and prevention must be made to successfully reduce or prevent childhood CAP.

    Cite as: Esposito S, Lelii M, Tenconi R, et al. Insights into antibiotic use in children with CAP. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 276–288 [https://doi.org/10.1183/2312508X.10019416].

  21. Page 289
    Abstract
    Tomislav Kostyanev, Dept of Medical Microbiology, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, S.625, 2610 Wilrijk, Antwerp, Belgium. E-mail: tomislav.kostyanev@uantwerpen.be

    Antimicrobial resistance has been recognised as a public health threat on a global scale, causing at least 700 000 death cases every year, which is predicted to increase to 10 million deaths per year in 2050 if no measures to contain antimicrobial resistance are taken. This rapidly spreading menace has made many antibiotics obsolete, which, together with the slow pace of clinical development of new antibacterials, has nearly desiccated the antibiotic pipeline, leaving fewer treatment options for many infections, including LRTIs. The few recently approved antibiotics and molecules in the final stages of clinical development could potentially be the light at the end of the tunnel for the treatment of LRTIs. Concerted action is needed to effectively confront antimicrobial resistance and deliver novel strategies for the treatment of infections caused by MDR bacteria. A multidisciplinary network, such as that created under the New Drugs for Bad Bugs programme, would play a crucial role in improving the efficiency of anti-infective trials.

    Cite as: Kostyanev T, Bonten MJM, Goossens H. New antibiotic development for pulmonary infections: New Drugs for Bad Bugs and beyond. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 289–301 [https://doi.org/10.1183/2312508X.10006116].

  22. Page 302
    Abstract
    Rodrigo Cavallazzi, Dept of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Louisville Health Sciences Center, Suite 310, 401 East Chestnut Street, Louisville, KY 40202, USA. E-mail: rodrigo.cavallazzi@louisville.edu

    HAP and VAP are common and associated with poor outcomes. They are characterised by a high prevalence of MDR organisms. As a result of these factors, combination therapy has been advocated for these conditions and this is the focus of our chapter. We present the theoretical advantages of combination therapy, review the clinical evidence related to combination therapy in HAP and VAP with an emphasis on RCTs where they were available, summarise the recommendations of the current guidelines for the management of HAP and VAP, and discuss the use of de-escalation therapy. We conclude with a description of our approach at University of Louisville Hospital, where we use combination therapy in all patients with HAP and VAP. We use empiric Gram-negative combination therapy with a β-lactam and a quinolone with the goal to increase the initial antimicrobial spectrum, and we use vancomycin or linezolid for coverage against MRSA. Microbiological studies are always used and de-escalation of therapy follows once these studies become available.

    Cite as: Cavallazzi R, Ramirez JA. Combination antibiotic therapy and synergy in HAP and VAP. In: Aliberti S, Chalmers JD, Pletz MW, eds. Anti-infectives and the Lung (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 302–311 [https://doi.org/10.1183/2312508X.10006216].

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