The global public health threat of antibiotic-resistant infections as well as the lack of new treatments in clinical development is a critical issue. Reasons for this include diminished commercial incentives for pharmaceutical companies to develop new antibiotics, which part-reflects a shift in antibiotic marketing paradigm from broad deployment to targeted therapy in relatively small patient populations. Such changes are encouraged by antimicrobial stewardship (AMS). Other factors include a lack of recognition in the traditional assessment of new antibiotics by regulators, health technology assessors and payers of the broad range of benefits of new agents, particularly their value to health care, economies and society. Recognising the seriousness of the situation, there have been recent changes and proposals by regulators for modification of the assessment process to accommodate a broader range of acceptable data supporting new drug applications. There is also increasing recognition by some payers of the societal benefit of new antibiotics and the need for financial incentives for those developing high-priority antibiotics. However, progress is slow, with recent publications focusing on industry and strategic perspectives rather than clinical implications. In this opinion piece, we therefore focus on clinicians and the practical steps they can take to drive and contribute to increasing awareness and understanding of the value of antibiotics. This includes identifying and gathering appropriate alternative data sources, educating on AMS and prescribing habits, and contributing to international antibiotic susceptibility surveillance models.

Telavancin was the first marketed lipoglycopeptide. Although licensed in Europe in 2011 for the treatment of nosocomial pneumonia caused by meticillin-resistant Staphylococcus aureus (MRSA), it did not become clinically available until March 2014. Given the limited clinical experience with telavancin in Europe, this review provides an overview of its antimicrobial and clinical activity as well as its position among today's antimicrobials, with particular focus on the implications of its licensing requirements. Telavancin has potent in vitro activity against isolates of Gram-positive pathogens, including MRSA and glycopeptide-intermediate S. aureus strains. In addition, at clinically attainable doses telavancin inhibits Gram-positive isolates of antibiotic-resistant strains from biofilm models. The in vitro potency of telavancin has been corroborated in the clinical setting. Comparative clinical studies of telavancin demonstrate non-inferiority compared with vancomycin in the treatment of hospital-acquired Gram-positive pneumonia, with high cure rates for telavancin-treated patients with monomicrobial S. aureus infection, including isolates with reduced vancomycin susceptibility. These studies also demonstrate an overall similar safety profile for telavancin and vancomycin, although importantly, patients with moderate-to-severe renal impairment at baseline are at greater risk for mortality with telavancin and this feature must be taken into account when selecting patients for its usage. In Europe, telavancin is a useful alternative for patients with difficult-to-treat, hospital-acquired MRSA pneumonia when there are very few alternatives. For example, it should be considered in such patients when vancomycin and linezolid are not suitable and where renal function permits.

BACKGROUND:Systemic Candida infections (SCI) occur predominantly in intensive care unit patients and are a common cause of morbidity and mortality. Recently, changes in Candida epidemiology with an increasing prevalence of SCI caused by Candida non-albicans species have been reported. Resistance to fluconazole and azoles in general is not uncommon for non-albicans species. Despite guidelines recommending initial treatment with broad-spectrum antifungals such as echinocandins with subsequent switch to fluconazole if isolates are sensitive (de-escalation strategy), fluconazole is still the preferred first-line antifungal (escalation) in many clinical practice settings. After diagnosis of the pathogen, the initial therapy with fluconazole is switched to a broad-spectrum antifungal if a non-albicans is identified. METHODS:The cost-effectiveness of initial treatment with micafungin (de-escalation) vs fluconazole (escalation) in patients with SCI was estimated using decision analysis based on clinical and microbiological data from pertinent studies. The model horizon was 42 days, and was extrapolated to cover a lifetime horizon. All costs were analyzed from the UK NHS perspective. Several assumptions were taken to address uncertainties; the limitations of these assumptions are discussed in the article. RESULTS:In patients with fluconazole-resistant isolates, initial treatment with micafungin avoids 30% more deaths and successfully treats 23% more patients than initial treatment with fluconazole, with cost savings of £1621 per treated patient. In the overall SCI population, de-escalation results in 1.2% fewer deaths at a marginal cost of £740 per patient. Over a lifetime horizon, the incremental cost-effectiveness of de-escalation vs escalation was £15,522 per life-year and £25,673 per QALY. CONCLUSIONS:De-escalation from micafungin may improve clinical outcomes and overall survival, particularly among patients with fluconazole-resistant Candida strains. De-escalation from initial treatment with micafungin is a cost-effective alternative to escalation from a UK NHS perspective, with a differential cost per QALY below the 'willingness-to-pay' threshold of £30,000.

Post-influenza bacterial pneumonia is a major cause of morbidity and mortality associated with both seasonal and pandemic influenza virus illness. However, despite much interest in influenza and its complications in recent years, good clinical trial data to inform clinicians in their assessment of treatment options are scant. This paucity of evidence needs to be addressed urgently in order to improve guidance on the management of post-influenza bacterial pneumonia. The objectives of the current article are to evaluate the emergence of the 2009 H1N1 influenza pandemic and use this information as background for an in-depth review of the epidemiology of bacterial pneumonia complicating influenza, to review the bacterial pathogens most likely to be associated with post-influenza bacterial pneumonia, and to discuss treatment considerations in these patients. When determining optimal management approaches, both antiviral and antibacterial agents should be considered, and their selection should be based upon a clear understanding of how their mechanisms of action intervene in the pathogenesis of post-influenza acute bacterial pneumonia.

Candidemia is among the leading causes of nosocomial bloodstream infections and is associated with significant mortality. Candida albicans is the commonest isolate and is uniformly sensitive to Fluconazole which is often the choice for initial empiric therapy. Candida glabrata, though numerically less common, may show reduced susceptibility to azoles including fluconazole.

Antibiotic de-escalation is a mechanism whereby the provision of effective initial antibiotic treatment is achieved while avoiding unnecessary antibiotic use that would promote the development of resistance. It is a key element within antimicrobial stewardship programs and treatment paradigms for serious sepsis. The embodiment of de-escalation is that based on microbiology results around the day 3 therapy point; the empiric antibiotic(s) that were started are stopped or reduced in number and/or narrowed in spectrum. Data are presented here which demonstrate that de-escalation is clinically effective and appropriate. However, the need for further studies, particularly in terms of realization of full benefits as well as implementation tools, is highlighted. De-escalation ought now to form a part of routine antimicrobial management, though how best to do it and the full breadth and scope of benefits remain to be identified.

One recent approach to facilitating guideline implementation involves the use of care bundles.This document presents a care bundle package addressing VAP prevention in an attempt to promote guideline-compliant practices. Uniquely, the development of these care bundles used a formalised methodology to assess the supporting data, based on multi-criteria decision analysis.The resulting VAP care bundles for prevention were: non-ventilatory circuit changes unless specifically indicated, alcohol hand hygiene, appropriately educated and trained staff, incorporation of sedation control and weaning protocols into patient care, and oral care with clorhexidine.Adoption of these care bundles should rationalise VAP prevention practises and improve outcomes, such as length of stay.

New information is available to improve antibiotic outcomes in severe sepsis where increasing resistance and reducing novel compound development make reaching the right decisions ever more difficult and important.

In modern sepsis management, long-held concerns about the inexorable rise of antimicrobial resistance have led to a key focus on antibiotic stewardship. Among the many strands that come together to provide a complete picture of stewardship is the issue of how antibiotic classes are deployed. Based on consistent results from mathematical modelling studies, the concept of a structured approach to such class use has evolved over the last decade. Whereas antibiotic cycling was initially perceived to be the strongest candidate for investigation in this field, over recent years the focus has shifted to antibiotic heterogeneity. Although there is presently little clinical work available on antibiotic heterogeneity, the available data demonstrate that this is an attractive option for enabling clinicians to make the most of their existing pool of antimicrobial classes by holding at bay, as much as possible, the emergence of resistance.

The global increase in antibiotic resistance is promoted by the widespread use of broad-spectrum antibiotics, creating a continuous selective pressure on bacteria. This resistance is depleting the number of effective antimicrobial agents. Since there have been few new agents active against Gram-negative bacteria in particular developed over the last two decades, it is important to make the most of existing antibiotics. Therefore, rational use of antimicrobial agents is vital in establishing a successful strategy to control and prevent both the clinical impact and the development of further resistance. Careful selection of the appropriate antimicrobial agent combined with correct dosing, duration of treatment and route of administration are all important to the success of this strategy and need to be coupled with antimicrobial resistance surveillance. Progress against the treatment strategy approach for optimising clinical outcomes whilst preventing antibacterial resistance based on antibiotic de-escalation will be reviewed with particular emphasis on the role of the carbapenems. This approach attempts to balance the need to provide appropriate initial treatment whilst limiting the emergence of antibacterial resistance.

These guidelines have been developed by a Working Party convened on behalf of the British Society for Antimicrobial Chemotherapy. Their aim is to provide general practitioners and other community- and hospital-based healthcare professionals with pragmatic advice about when to suspect MRSA infection in the community, when and what cultures should be performed and what should be the management options, including the need for hospitalization.

In February 2006 the Department of Health announced that routine pneumococcal vaccine was to be introduced into the normal UK childhood immunisation programme. This article reviews the history of pneumococcal vaccination and its effectiveness in both the vaccine recipients and the population as a whole.

Surveillance studies provide important information that allows for the identification of trends in pathogen incidence and antimicrobial resistance, including identification of emerging pathogens at national and global levels. Routine surveillance is critical for creating and refining approaches to controlling antimicrobial resistance and for guiding clinician decisions regarding appropriate treatment. The traditional approach has been to monitor pathogen antimicrobial susceptibility; numerous large studies have been performed, and their designs have evolved over time. Longitudinal studies are particularly useful because important information can be obtained by comparing data over time. Another approach to surveillance, that of monitoring antimicrobial use, can help to identify trends in dosing, to prevent the development of resistance. Several studies have incorporated this approach into their methods, and both large and small studies have attempted to correlate antimicrobial use data with antimicrobial resistance data. Overall, care must be taken to coordinate programs for optimal utilization of resources, to avoid duplication of effort.

The Hospital Pharmacy Initiative was a 12 million pounds sterling scheme introduced in England in 2003 and aimed at improving antimicrobial prescribing. Although significant successes have been claimed for the scheme, there is evidence which demonstrates that the untargeted and essentially undirected investment where no clear objectives were set has resulted in extremely variable developments with arguably minimal gains attributable to the programme. This contrasts strongly with the Scottish approach where form and function has been detailed with a focus on service sustainability in the ongoing challenge of improving prudent antimicrobial prescribing.

The recent increase in hospital-acquired infections (HAIs) has meant that hospital-acquired pneumonia (HAP) has come under the spotlight. HAP is the most common HAI contributing to death and affects about 0.5-1% of all patients admitted to hospital. HAP significantly increases health complications and extends the length of time patients stay in hospital by up to 13 days on average, thus impacting significantly on hospital resources. The British Society of Antimicrobial Chemotherapy Hospital-Acquired Pneumonia guidelines were published on the society's website last year and represent one of only two sets of evidence-based HAP guidelines in the world which deal with the trio of prevention, diagnosis and treatment. This paper reviews the evolution and status of HAP guidelines, drawing attention to recent developments, differences in approach and outcomes and further areas of work. There are clear indications that the implementation of evidence-based guidelines will reduce HAP and improve patient outcomes.

This overview provides a summary of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program over an 8-year period from 1997 to 2004. The evolution of the MYSTIC Program is described, as well as its design compared with other surveillance programs. In addition, the global MYSTIC Program data, published to date, are summarized, and the empiric use of carbapenems, their current indications, and meropenem usage versus resistance was discussed. From 1997 to 2004, 120 medical centers that were actively prescribing meropenem in 32 countries worldwide participated in the program. The MYSTIC Program results demonstrate the sustained potency and continued effectiveness of meropenem globally against clinically relevant Gram-negative and Gram-positive pathogens including extended spectrum β-lactamase– and AmpC β-lactamase–producing organisms, which may also display resistance to the fluoroquinolones and/or aminoglycosides. Furthermore, in centers actively prescribing meropenem, resistance to meropenem is not increasing despite greater resistance among the comparator antimicrobial agents. Thus, antipseudomonal carbapenems such as meropenem and imipenem remain an effective treatment option.

In the present battle against the rising tide of resistance, several interventions have been proposed to help control the situation. One of these is a process of planned antibiotic restriction, introduced through cycling drug selection based on local surveillance. Although such antibiotic cycling has been the subject of much discussion for 20 years, there are relatively few data available to assess its worth. A recent systematic review found only four studies worthy of inclusion and concluded that antibiotic cycling could not, at present, be promoted as a methodology to control resistance. This paper considers the complete literature and through demonstrating consistent benefits across the breadth and depth of the findings, suggests that whereas further work is required, nevertheless antibiotic cycling—as part of a suite of control measures—is a valid option.

An omnibus survey of microbiologists (n = 400) and a survey of participants (n = 49) in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme were conducted to determine the awareness and prevalence of extended-spectrum beta-lactamases (ESBLs), and the regularity and method of screening. Of the omnibus survey participants, 69% screened regularly for ESBLs, compared with 83% of MYSTIC participants. In both surveys, ESBLs were more common in Klebsiella pneumoniae (73% and 79%, respectively) and Escherichia coli (63% and 81%, respectively) than in other bacteria. The surveys demonstrated that awareness of, and testing for, ESBLs is inconsistent.