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Respiratory infections are among the most common reasons for prescribing antibiotics. The excessive use of antibiotics in ambulatory practice has contributed to the emergence and spread of antibiotic resistance. The appropriate use of antimicrobial agents for respiratory infections could potentially reduce the emergence of antibiotic resistance. This article reviews recent guidelines and position papers on the appropriate antibiotic treatment for respiratory infections. There is a wide consensus that antibiotics are not appropriate for the treatment of most cases of acute bronchitis, pharyngitis, and rhinosinusitis. The recently published community-acquired pneumonia guidelines emphasized the importance of selecting antibiotic regimens active against both typical and atypical pathogens. However, there is disagreement regarding the routine use of the new quinolones.

PURPOSE OF REVIEW: Central nervous system (CNS) infections such as ventriculitis and meningitis are associated with significant morbidity and mortality. In part, this may be due to increased difficulties in achieving a therapeutic antibiotic concentration at the site of infection due to both the pharmacokinetic (PK) changes observed during critical illness and the reduced antibiotic penetration through the blood brain barrier. This paper reviews the pharmacodynamics (PD) and CNS PKs of antibiotics used for Gram-negative bacterial CNS infections to provide clinicians with practical dosing advice. RECENT FINDINGS: Recent PK studies have shown that currently used intravenous antibiotic dosing regimens may not achieve a therapeutic exposure within the CNS, even for reportedly 'susceptible' bacteria per the current clinical meningitis breakpoints. Limited data exist for new β-lactam antibiotic/β-lactamase inhibitor combinations, which may be required for multidrug resistant infections. Intraventricular antibiotic administration, although not a new concept, has further evidence demonstrating improved patient outcomes compared with intravenous therapy alone, despite the ongoing paucity of PK studies guiding dosing recommendations. SUMMARY: Clinicians should obtain the bacterial minimum inhibitory concentration when treating patients with CNS Gram-negative bacterial infections and consider the underlying PK/PD principles when prescribing antibiotics. Therapeutic drug monitoring, where available, should be considered to guide dosing. Intraventricular therapy should also be considered for patients with ventricular drains to optimise clinical outcomes.

Purpose of review A number of pharmacokinetic and pharmacodynamic factors in critically ill or severely immunosuppressed patients influence the effectiveness of antifungal therapy making dosing less certain. Recent position papers from infectious diseases societies and working groups have proposed methods for dosage individualization of antibiotics in critically ill patients using a combination of population pharmacokinetic models, Monte-Carlo simulation and therapeutic drug monitoring (TDM) to guide dosing. In this review, we examine the current limitations and practical issues of adapting a pharmacometrics-guided dosing approaches to dosing of antifungals in critically ill or severely immunosuppressed populations. Recent findings We review the current status of antifungal susceptibility testing and challenges in incorporating TDM into Bayesian dose prediction models. We also discuss issues facing pharmacometrics dosage adjustment of newer targeted chemotherapies that exhibit severe pharmacokinetic drug-drug interactions with triazole antifungals. Summary Although knowledge of antifungal pharmacokinetic/pharmacodynamic is maturing, the practical application of these concepts towards point-of-care dosage individualization is still limited. User-friendly pharmacometric models are needed to improve the utility of TDM and management of a growing number of severe pharmacokinetic antifungal drug-drug interactions with targeted chemotherapies.

Quality and safety of care are national priorities. Healthcare-acquired infections are now considered preventable and unacceptable. Care bundles are used to prevent and treat health-care acquired infections in adults. This paper considers the evidence and context for their use in children.There is evidence that care bundles are effective in the adult literature. There have been few reports in the paediatric literature on the implementation of care bundles in children. Paediatric reports focus on the impact of interventions to reduce ventilator-associated pneumonia and central line infections. Recent articles suggest that care bundles are beneficial as part of a comprehensive improvement programme in the ICU. Other papers confirm that ventilator-associated pneumonia bundles can be translated from adults to children, supporting the business case for improving quality.The adult and paediatric literature agree that care bundles are valuable tools for ensuring that evidence-based medicine is delivered reliably. Care bundles should be adopted in paediatric and neonatal units. In particular, if applied correctly, they are likely to significantly reduce certain health-care acquired infections. Further research is needed to refine the individual elements of the bundles and to evaluate new applications for them.

Purpose Tuberculous meningitis is a devastating infection that is hard to diagnose and treat. We have reviewed tuberculous meningitis original research published within the last 18 months, selecting papers which we consider have most advanced knowledge. Recent findings We review advances in diagnostic methods, anti-tuberculosis chemotherapy, and the common complications of tuberculous meningitis. New commercial molecular diagnostic tests, such as GeneXpert MTB/RIF, have an important role in tuberculous meningitis diagnosis, but as with all other available tests they lack sensitivity and cannot rule out the disease. Recent trials and pharmacokinetic studies have advanced understanding of the best anti-tuberculosis drug regimens for tuberculous meningitis, although optimal doses and duration remain uncertain, especially for young children. Good outcomes depend upon the careful management of the common complications (brain infarcts, tuberculomas, hydrocephalus and hyponatraemia) and controlling intracranial pressure. New tools, such as point-of-care ultrasound, may assist in the management, especially in the assessment of intravascular volume and raised intracranial pressure. Summary Disability-free survival from tuberculous meningitis depends upon rapid diagnosis, starting anti-tuberculosis drugs before the onset of coma, and managing complications. Progress is slow and threatened by emerging drug resistant bacteria, but new drugs and diagnostic technologies offer hope to future patients.

Purpose of review The present review summarizes some of the key papers on the prevention of surgical site infections (SSI) published in 2008. Recent findings The National Institute for Health and Clinical Excellence published guidelines on the prevention and management of SSI. These guidelines follow a similar format to those published previously. There are, however, some important differences to previous recommendations and these are outlined in this current article. Other publications have provided additional evidence that suggests certain antiseptic agents are more efficacious than others for surgical hand antisepsis. Staphylococcus aureus decolonization has also been studied and noted to be of benefit for the prevention of SSI. Other research studies have focused on patient homeostasis, including the use of supplemental perioperative oxygen, which has resulted in mixed findings. Finally, the use of surveillance to evaluate the efficacy of 'care bundles' has been reported, which brings together many different approaches for the prevention of SSI. Summary Several evaluations of pre, peri and postoperative strategies for the prevention of SSI have been published in 2008, some of which have raised some fundamental questions.

Purpose of review To identify recent papers showing how human and parasite genetics influence leishmaniasis, and how understanding of the immunopathology may be utilized in immunotherapy for these diseases. Recent findings Progress has been made in recent years showing the complexity within populations of Leishmania spp. and indicating that different strains lead to diverse clinical pictures and responses to treatment. Thus detection of parasite genetic tags for the precise identification of infecting strains, and for predictive diagnosis of clinical and therapeutic fates seems now possible. Host genetic loci involved in disease outcome have been detected, which may also be explored for better case management. These developments in diagnosis will demand expanding the therapeutic arsenal to take their expected effect. This is starting to be fulfilled by immunotherapies successfully employed to treat cases refractory to standard first line drugs, as the result of a more profound comprehension of the immunopathology of the leishmaniases. Summary The knowledge mounting has already helped explain why different patients present different forms of leishmaniasis and respond differently to treatment, and may be on the verge of catalyzing a major change in the already over a century old paradigm of diagnosing and managing these patients.

PURPOSE OF REVIEW: Despite diagnostic and therapeutic advances, acute haematogenous osteomyelitis in children continues to cause significant morbidity and disease burden. The molecular epidemiology of causal organisms has wide geographic variation, but regardless of cause children often require several weeks of inpatient parenteral antibiotic therapy. This review focuses on antibiotic treatment and length of antibiotic therapy. RECENT FINDINGS: Currently there is no international and little local consensus regarding the route or duration for antibiotic treatment of acute haematogenous osteomyelitis in children. Although there are encouraging data from review papers and case series, no randomized controlled trial has been conducted to show good evidence for shorter courses of parenteral antibiotic treatment. Prospective studies show effective treatment for a wide variety of antibiotic agents, but there are few comparative studies. Overall treatment for 4-6 weeks is considered standard therapy, but the laboratory or clinical parameters that would determine the decision to switch to oral therapy remain undefined. SUMMARY: Evidence-based data about the route and duration of intravenous antibiotic treatment for acute haematogenous osteomyelitis in children are still limited to observational and retrospective studies. A randomized controlled trial will provide much needed data

Purpose of review Community-acquired pneumonia (CAP) is associated with significant morbidity and mortality and is the most common cause of death from infectious diseases. CAP patients requiring intensive care unit (ICU) admission carry the highest mortality rates. This paper aims to review the current literature regarding epidemiology, risk factors, severity criteria and reasons for admitting the hospitalized patient to the ICU, and the empiric and specific antibiotic therapeutic regimens employed. Recent findings Multiple sets of clinical practice guidelines have been published in the past few years addressing the treatment of CAP. The guidelines all agree that CAP patients admitted to the hospital represent a major concern, and appropriate empiric therapy should be instituted to improve clinical outcomes. Summary The cost, morbidity and mortality of CAP patients requiring ICU admission remain unacceptably high. These are heterogeneous groups of patients, so it is important to use risk-stratification based on clinical parameters and prediction tools. Appropriate antibiotic therapy is an important component in the management of both groups of patients. In particular, it is essential to administer an appropriate antimicrobial agent from the initiation of therapy, so that the risks of treatment failure and the morbidity of CAP may be minimized.

Purpose of review As new antifungal agents were introduced for the treatment of fungal infections, reliable methods were developed or adapted for the in-vitro susceptibility testing of yeasts and moulds (filamentous fungi). This paper reviews the available methods for antifungal susceptibility testing of moulds as well as the scant data that have been published since 2002 regarding the clinical implications of in-vitro testing. Recent findings Caspofungin and voriconazole have been recently licensed for treatment of certain mould infections that are usually refractory to treatment with established agents. The introduction of new agents and the frequent reports of mould resistance have underscored the role of the laboratory in patient management and initiated the study of mechanisms of resistance in moulds. In 2002, the US National Committee for Clinical Laboratory Standards M38-P document moved to the approved level of development (M38-A document). Although combination therapy and synergistic studies with the new agents have been documented, very little information is available on in-vitro/in-vivo correlations for moulds. Summary The ultimate goal of in-vitro testing is the prediction of the clinical outcome of therapy. The use of National Committee for Clinical Laboratory Standards procedures has led to increased interlaboratory agreement of minimum inhibitory concentrations. Reproducibility of minimum inhibitory concentrations for yeasts has facilitated the establishment of interpretive breakpoints for fluconazole and itraconazole versus Candida spp., but breakpoints are not available for any antifungal against mould species. Although some insights have been documented regarding the potential utility of in-vitro testing for moulds, further documentation of in-vitro versus in-vivo data is needed.

Solid organ transplantation is emerging as a life-saving procedure for increasing numbers of patients and invasive fungal infections are a significant cause of mortality and morbidity for patients undergoing these procedures. This paper will review the latest data pertinent to the development of effective regimens aimed at preventing invasive mycoses in the solid organ transplantation population.Risks for developing invasive fungal infections are continuing to evolve, leading to shifts in the epidemiology of invasive mycoses occurring after transplantation. For instance, risks for the development of invasive candidiasis in the immediate postoperative period following orthotopic liver transplantation have decreased dramatically while the incidence of invasive aspergillosis appears to be on the rise. New agents have recently been approved for use in the United States and may have a role in prophylactic strategies aimed at preventing these fungal infections.An understanding of these issues is crucial to the development of targeted prophylactic regimens for the successful prevention of invasive fungal infections in the solid organ transplant recipient.

Purpose of the review The present review covers the literature on prevention of surgical site infections published during 2001. Only papers that offer new insights or question current recommendations are included. Recent findings The most interesting advances have been made in the preoperative preparation of the patient. In particular, the effects of preoperative warming of the patient, either generally or locally at the incision site, on the rate of surgical site infections are impressive and warrant further investigation. Also, the effects of strict control of perioperative blood glucose levels and of preoperative eradication of nasal carriage of Staphylococcus aureus should be studied in greater detail. Summary The protective effect of local and systemic warming before surgical procedures has been described in two well designed studies. Although a final judgement regarding effectiveness can only be made after more extensive investigations have been conducted, there appear to be few arguments against application of this cheap and safe measure. Thus, implementation of preoperative warming can be justified in settings associated with high rates of surgical site infections.

The numbers of cancer patients subjected to chemotherapy-induced neutropenia steadily grows as the new indications for systemic treatment expand. When these patients develop fever, or other signs of infection, they must receive immediate medical attention. This paper discusses the current therapeutic strategy for febrile neutropenia in cancer patients and reviews some of the newer approaches, which include empirical monotherapy, outpatient protocols, antibiotic prophylaxis and the use of haematopoietic growth factors.

The aim is to review recent literature on 'test-and-treat', a prevention strategy that promotes high levels of HIV testing and initiating antiretroviral therapy upon diagnosis, regardless of CD4 cell count. Antiretroviral therapy (ART) has been shown to dramatically reduce viral load which is strongly associated with the risk of transmission, therefore there is the potential to reduce HIV transmissions with ART.Recent papers from observational studies on heterosexual sero-discordant couples found an overall rate of transmission of HIV-1 from ART-treated patients of 0.46 per 100 person-years, confirming the possibility of using ART as a prevention strategy. Several models have been used to predict the effect of this strategy and the potential risks of it. Randomized controlled trials are currently ongoing investigating the effect of ART on reducing infectiousness and the feasibility of this policy.More precise estimations of the transmission risk under virally suppressive ART (especially in MSM) and of change in sex risk behaviour at diagnosis and at start of ART are needed. Further, the benefit to individual health of very early ART initiation and the feasibility of this policy need to be evaluated. Achieving very high levels of testing should be a high priority due to the benefits of initiating ART in all those who are in need (CD4 cell count350 cells/μl) and potential benefits on incidence due to reductions in risk behaviour in those diagnosed. Use of ART immediately at diagnosis in those with high CD4 cell counts should await results from further studies.

As antiretroviral therapy scale-up proceeds in developing countries, simple and inexpensive procedures are required to monitor the prevalence and transmission of drug-resistant HIV strains to ensure optimal use of antiviral therapy. This article reviews new surveillance methods and practices used to monitor drug resistance in the developing world.Several recently published studies report the successful development of methods using dried blood spots, collected on filter paper, for HIV drug resistance genotyping tests. In concert to antiretroviral therapy rollout, the WHO has developed a laboratory network and sought to implement surveillance of transmitted drug resistance in developing countries. A small number of developing world prevalence studies have thus far been published using dried blood spots. These studies reveal low rates of transmitted drug resistance. Other studies indicate that the use of dried blood spots for HIV drug resistance surveillance may possibly lead to overestimates.The use of dried blood spots as a method of specimen collection and storage is simple, inexpensive and is an appropriate technique for the surveillance of transmitted HIV drug resistance.

Purpose of review Clostridium difficile infection and Clostridium difficile-associated diarrhea (CDAD) are growing worldwide health threats. Recent studies have identified new host risk factors, diagnostic approaches and therapies of CDAD. The present review focuses on scientific papers published in the past 18 months in an attempt to provide the latest information on the topic. Recent findings We are seeing an increasing number of patients with Clostridium difficile infection developing their illness in the community, although many were recently discharged from a healthcare setting suggesting an acquisition of infection in the hospital environment. The use of gastric acid-altering drugs that facilitate intestinal transit of the bacteria, antibacterial drugs that deplete colonic flora and presence of inflammatory bowel disease are risk factors for CDAD. Fulminant CDAD is increasing, complicated by leukocytosis (peripheral white blood cell count >16,000/mm), hypoalbuminemia, renal failure and emergency colectomy, with overall rise in CDAD disease mortality rates. Although vancomycin is recommended for severe cases of CDAD, recurrence rates remain high. Control of Clostridium difficile infection in the hospital setting focuses on disinfection of the environment and antibiotic stewardship policies. Anti-Clostridium difficile vaccines are in development. Summary CDAD is an increasing health problem throughout the United States, Canada and Europe with rising mortality rate. Occurrence of CDAD outside of healthcare settings and in pediatric populations represents newly emerging problems. New treatments are needed.

Efforts to reduce hospitalization or the length of stay are common topics in papers published last year. Chlamydia pneumoniae is now recognized worldwide as a common pathogen in community-acquired pneumonia. A great variation in the frequency of various pathogens is found in different countries, stressing the importance of ascertaining the aetiological and epidemiological situation in each respective country.

Purpose of review Access to treatment is a multi-step process and little progress has been made to improve treatments for sleeping sickness over the past 50 years. The current strategy is based on diagnostic tools developed in the 1960s while available drugs are still the same as those developed in the middle of the last century. Strategic opportunities can only be based on two achievements: improved diagnosis and safer drugs. This paper reviews the development of new diagnostic tools and drugs and the opportunity offered by new technologies for their further improvement. Recent findings The prodrug DB289 shows excellent oral activity with low toxicity for the treatment of early-stage sleeping sickness; it has recently entered phase II(b) clinical trials. The recent ability to identify and test specific host and parasite biomarkers has allowed the development of new, more-specific and sensitive, diagnostic and stage-determination tools. The accurate diagnosis of an infection by use of proteomic signature analysis has been achieved. Urinary nitrites and nitrates follow closely the increase of brain nitric oxide associated with the penetration of trypanosomes in the brain. Sleep-onset rapid eye movement-like episodes have been shown to occur at onset of late-stage trypanosomiasis. This unique disturbance of the wake/sleep cycle seems to be the first pathognomonic sign in the occurrence of late-stage trypanosomiasis. Summary Following the description of the disease, and diagnostic tools and drugs that have been used, and are still in use today, the authors show how it has influenced over time the evolution of strategies for surveillance and control. Recent developments and prospects for new, more-specific and sensitive diagnostic tools and a safer drug will undoubtedly improve the accuracy of patient recruitment and facilitate treatment, and provide ways towards new strategic opportunities.

PURPOSE OF REVIEW: In the majority of countries costs for health care are increasing and strategies to reduce adverse events in medical treatment have an increasing importance. Nosocomial infection remains the most common type of complication affecting hospitalized patients. As preventive strategies have indeed become more important they now have to show not only that they are effective in reducing nosocomial infections but also that they are cost effective. This paper investigates the contribution made by articles published in the last year to the development of nosocomial-infection surveillance and control policies. RECENT FINDINGS: At least 15 randomized controlled studies and six meta-analyses investigating various infection-control policies were published last year. They did not lead to any changes in present guidelines, but rather endorsed existing recommendations. At least nine studies were found reporting a substantial reduction in nosocomial infections by the introduction of quality management principles under routine working conditions. Furthermore there were a lot of studies published which focused on optimizing surveillance measures and investigating the use of reference data for reducing infection rates. Only seven studies estimating the burden of disease were found in the literature of the past year. SUMMARY: The predominant opinion voiced in the studies was that in many medical institutions some 30% or more of nosocomial infections could be prevented.

Immunocompromised patients are at risk of developing fungal infections. Over time, the incidence of fungal infections and the spectrum of causative organisms have changed. In addition, treatment strategies in this high-risk population have also changed. Traditional approaches (using polyene-based therapy and older azoles), including empirical treatment strategies, have evolved to include prophylaxis in populations at the greatest risk. These strategies, although effective against Candida species, have not really impacted infections caused by Aspergillus spp. With the recent approval of antifungal agents with demonstrated activity against Aspergillus and other mould infections, there is hope for better outcomes in the treatment of established infections. Several agents, with activity against Aspergillus, have been shown to be effective in the empirical setting. The role of these new antifungal agents in the prophylactic setting remains unknown at present, but the potential for reducing Aspergillus infections is promising and requires ongoing study. The other area of significant research in fungal infections has been the search for accurate, non-invasive, rapid diagnostic tests. Over the past year, several publications have indicated that early diagnosis is possible in immunocompromised patients. These new diagnostics have paved the way for a new strategy, called pre-emptive therapy, enabling infected patients to be identified at an earlier stage of infection. This strategy will permit targeted antifungal therapy in those at greatest risk, and will avoid unnecessary, potentially toxic therapy in those not infected. Validations of the various techniques show promise and are reviewed in this paper.

Purpose of review Prion diseases such as Creutzfeldt-Jakob disease represent a unique infection control problem because prions exhibit an unusual resistance to conventional chemical and physical decontamination methods. This paper reviews the recent literature and provides recommendations for the prevention of nosocomial transmission of prion agents. Recent findings Recommendations to prevent the cross-transmission of infection from medical devices potentially contaminated with prions have been based primarily on prion inactivation studies. Newer recommendations consider inactivation data, but also use epidemiological studies of prion transmission, the infectivity of human tissues, and the efficacy of removing microbes by cleaning. Prion-specific disinfection/sterilization is required in only limited settings. Healthcare workers are not at risk of acquiring transmissible spongiform encephalopathies. Blood or blood products have not been demonstrated to be vehicles for transmission. Summary On the basis of scientific data, only critical (e.g. surgical instruments) and semicritical devices contaminated with high-risk tissue (i.e. brain, spinal cord, eye) from high-risk patients (e.g. with known or suspected Creutzfeldt-Jakob disease) require special treatment.