Controlling clostridium difficile

Clostridium difficile infection causes colitis and is closely associated with the use of antimicrobials, probably due to disruption of the normal bowel flora. Avoiding inappropriate antimicrobial use is the most important way to prevent this potentially life-threatening infection. Emergent hypervirulent variants of C. difficile are associated with increased transmission, morbidity and mortality and have caused epidemics in North America and Europe. Cases have also been reported in Australia so intensified surveillance and antimicrobial stewardship is more important than ever. While any antimicrobial can precipitate C. difficile, fluoroquinolones, clindamycin and cephalosporins are particularly implicated. Other drugs, such as proton pump inhibitors, have also been associated with an increased incidence of C. difficile. Severe disease is managed in hospital. For non-severe disease, treatment generally includes supportive measures and treatment with oral metronidazole. Relapse is common

Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis

PURPOSE: Early recognition and effective treatment of sepsis improves outcomes in critically ill patients. However, antibiotic exposures are frequently suboptimal in the intensive care unit (ICU) setting. We describe the feasibility of the Bayesian dosing software Individually Designed Optimum Dosing Strategies (ID-ODS™), to reduce time to effective antibiotic exposure in children and adults with sepsis in ICU. METHODS: A multi-centre prospective, non-randomised interventional trial in three adult ICUs and one paediatric ICU. In a pre-intervention Phase 1, we measured the time to target antibiotic exposure in participants. In Phase 2, antibiotic dosing recommendations were made using ID-ODS™, and time to target antibiotic concentrations were compared to patients in Phase 1 (a pre-post-design). RESULTS: 175 antibiotic courses (Phase 1 = 123, Phase 2 = 52) were analysed from 156 participants. Across all patients, there was no difference in the time to achieve target exposures (8.7 h vs 14.3 h in Phase 1 and Phase 2, respectively, p = 0.45). Sixty-one courses in 54 participants failed to achieve target exposures within 24 h of antibiotic commencement (n = 36 in Phase 1, n = 18 in Phase 2). In these participants, ID-ODS™ was associated with a reduction in time to target antibiotic exposure (96 vs 36.4 h in Phase 1 and Phase 2, respectively, p < 0.01). These patients were less likely to exhibit subtherapeutic antibiotic exposures at 96 h (hazard ratio (HR) 0.02, 95% confidence interval (CI) 0.01-0.05, p < 0.01). There was no difference observed in in-hospital mortality. CONCLUSIONS: Dosing software may reduce the time to achieve target antibiotic exposures. It should be evaluated further in trials to establish its impact on clinical outcomes

Optimising Treatment Outcomes for Children and Adults Through Rapid Genome Sequencing of Sepsis Pathogens. A Study Protocol for a Prospective, Multi-Centre Trial (DIRECT)

BackgroundSepsis contributes significantly to morbidity and mortality globally. In Australia, 20,000 develop sepsis every year, resulting in 5,000 deaths, and more than AUD$846 million in expenditure. Prompt, appropriate antibiotic therapy is effective in improving outcomes in sepsis. Conventional culture-based methods to identify appropriate therapy have limited yield and take days to complete. Recently, nanopore technology has enabled rapid sequencing with real-time analysis of pathogen DNA. We set out to demonstrate the feasibility and diagnostic accuracy of pathogen sequencing direct from clinical samples, and estimate the impact of this approach on time to effective therapy when integrated with personalised software-guided antimicrobial dosing in children and adults on ICU with sepsis.MethodsThe DIRECT study is a pilot prospective, non-randomized multicentre trial of an integrated diagnostic and therapeutic algorithm combining rapid direct pathogen sequencing and software-guided, personalised antibiotic dosing in children and adults with sepsis on ICU.Participants and interventionsDIRECT will collect microbiological and pharmacokinetic samples from approximately 200 children and adults with sepsis admitted to one of four ICUs in Brisbane. In Phase 1, we will evaluate Oxford Nanopore Technologies MinION sequencing direct from blood in 50 blood culture-proven sepsis patients recruited from consecutive patients with suspected sepsis. In Phase 2, a further 50 consecutive patients with suspected sepsis will be recruited in whom MinION sequencing will be combined with Bayesian software-guided (ID-ODS) personalised antimicrobial dosing.Outcome measuresThe primary outcome is time to effective antimicrobial therapy, defined as trough drug concentrations above the MIC of the pathogen. Secondary outcomes are diagnostic accuracy of MinION sequencing from whole blood, time to pathogen identification and susceptibility testing using sequencing direct from whole blood and from positive blood culture broth.DiscussionRapid pathogen sequencing coupled with antimicrobial dosing software has great potential to overcome the limitations of conventional diagnostics which often result in prolonged inappropriate antimicrobial therapy. Reduced time to optimal antimicrobial therapy may reduce sepsis mortality and ICU length of stay. This pilot study will yield key feasibility data to inform further, urgently needed sepsis studies. Phase 2 of the trial protocol is registered with the ANZCTR (ACTRN12620001122943).Trial registrationRegistered with the Australia New Zealand Clinical Trials Registry Number ACTRN1262000112294

Mefloquine

Mefloquine is available as a hydrochloride salt of the structure depicted in Figure 178.1 (Roche, 2003a). Its official chemical name is (R*, S*)-(±)-α-2-piperidnyl-2,8-bis (trifluromethyl)- 4-quinolinemethanol hydrochloride (Roche, 2003a). Mefloquine is a white crystalline solid with a molecular weight of 418 (Roche, 2003a). The compound has two chiral centers, and there are four isomeric forms. The commercially available formulation is a racemate of the 11R,2‘S and 11S,2‘R enantiomers

The rise and rise of antimicrobial resistance in Gram-negative bacteria

Antimicrobial resistance is a major threat to the delivery of effective care and already causes 700 000 excess deaths per year worldwide. International consensus on action to combat antimicrobial resistance was reached in 2015. Australia is implementing a national strategy. The clinical consequences of antimicrobial resistance are seen most acutely in multi-drug resistant Gram-negative bacterial infections, where they cause increased mortality and morbidity and threaten the delivery of once routine medical care. The solution to antimicrobial resistance is complex and multifaceted. Antimicrobial stewardship, that is optimising the use of the antibiotics we currently have, is the most rapidly deployable mitigation. Several novel antibiotics with activity against a range of drug-resistant bacteria are now available clinically, leading to hope that innovative solutions will reduce the impact of resistance. It is critical that these new drugs are protected from inappropriate use

Epidemiology and clinical outcomes of Hepatitis delta (D) virus infection in Queensland, Australia

To investigate the epidemiology, clinical characteristics and outcomes of those with hepatitis delta virus (HDV) infection in Queensland, Australia.Retrospective cohort study of individuals tested for HDV between 1997 and 2016 in the public healthcare system in Queensland.179 individuals recorded positive HDV serology between 1997 and 2016, with a total of 4407 individuals undergoing testing (seroprevalence 4.1%). The majority of HDV positive individuals were male and were born overseas. Those born in Africa had a higher risk ratio (RR) for HDV infection (RR, 1.55; 95% CI, 1.14-2.09); being born in Asia was associated with a relatively lower risk of HDV infection (RR, 0.36; 95% CI, 0.27-0.58). Positive hepatitis C virus (HCV) serology was significantly associated with positive HDV serology (RR, 2.98; 95% CI, 2.36-3.78). Of the HDV positive individuals born in Australia, the majority were HCV positive (69.8%). HDV positive individuals were less likely to be Hepatitis B e antigen (HBeAg) positive (RR, 0.64; 95% CI, 0.45-0.93) and recorded lower hepatitis B virus (HBV) viral loads. Positive HDV serology was associated with increased risk of liver cirrhosis (RR, 2.3; 95% CI 1.73-3.07) and liver transplantation (RR, 1.93; CI 1.31-2.85). Only 8% of HDV positive individuals underwent HDV treatment.In Queensland, HDV seropositivity is associated with overseas birth, particularly in Africa. HDV infection is associated with decreased HBV viraemia and more advanced liver disease

Rickettsia Australis and Queensland tick typhus: a rickettsial spotted fever group infection in Australia

Rickettsia australis, the etiologic agent of Queensland tick typhus (QTT), is increasingly being recognized as a cause of community-acquired acute febrile illness in eastern Australia. Changing human population demographics, climate change, and increased understanding of expanding vector distribution indicate QTT is an emerging public health threat. This review summarizes the epidemiology, pathogenesis, clinical features, treatment principles, and future directions of this disease. Increased recognition of QTT will enable consideration of and prompt treatment of R. australis infection by clinicians in Australia

Epidemiology and characteristics of Rickettsia australis (Queensland tick typhus) infection in hospitalized patients in North Brisbane, Australia

Queensland Tick Typhus (QTT; ) is a Spotted Fever Group (SFG) rickettsial infection endemic to Australia. It is an underreported and often unrecognized illness with poorly defined epidemiology. This article describes epidemiological features and the geographical distribution of QTT in hospitalized patients. Cases of QTT were identified retrospectively from 2000⁻2015 at five sites in Northern Brisbane through a pathology database. Included cases had a four-fold rise in SFG-specific serology, a single SFG-specific serology ≥256 or an SFG-specific serology ≥128 with a clinically consistent illness. Of the fifty cases identified by serology, 36 were included. Age ranged from 3⁻72 years (with a mean of 39.5 years) with a male-to-female ratio of 1:1.1. Fifteen of 36 (42%) study participants had hobbies and/or occupations linked with the acquisition of the disease. Seventeen of 36 (47%) identified a tick bite in the days preceding presentation to hospital, and reported exposure to a known animal host was minimal (25%). QTT infection occurred throughout the year, with half reported between April and July. Recent ecological and sociocultural changes have redefined the epidemiology of this zoonotic illness, with areas of heightened infection identified. Heightened public health awareness is required to monitor QTT disease activity