Nosocomial pneumonia in the critically III

Despite the large body of published work emphasising the importance of nosocomial pneumonia its true significance with respect to mortality is difficult to assess. This partially stems from the limitations imposed by clinical diagnostic criteria and from the interpretation of multivariate analyses which in themselves can only confirm correlations and associations. Two key questions need to be resolved. First, what is the true incidence of nosocomial pneumonia? Microbiological data would suggest the incidence to be much lower than previously suspected and this view is supported by the relative rarity of severe lung infections manifested as lung cavitation, empyema or bacteraemia. Second, what is the true mortality attributable to nosocomial pneumonia? Clinical studies need to examine the mode of death and not just confirm the presence of pneumonia at the time of death. Only in cases where overwhelming lung infection leads to an inability to maintain respiratory or haemodynamic homeostasis can death be genuinely attributed to nosocomial pneumonia. Clinical experience suggests that the attributable mortality is low, an impression that is reinforced by the relatively small impact of selective decontamination of the digestive tract (SDD) upon survival in patients with nosocomial pneumonia. Until these questions are answered satisfactorily it is appropriate to take reasonable measures to prevent nosocomial pneumonia but to embark on antibiotic therapy only when there is supportive microbiological evidence or in the presence of clinically indisputable lung infection. © 1991 Longman Group UK Ltd

Antibiotic use and clinical outcomes in the acute setting under management by an Infectious Diseases Acute Physician versus other clinical teams: a cohort study

Objectives To assess the magnitude of difference in antibiotic use between clinical teams in the acute setting and assess evidence for any adverse consequences to patient safety or healthcare delivery. Design Prospective cohort study (1 week) and analysis of linked electronic health records (3 years). Setting UK tertiary care centre. Participants All patients admitted sequentially to the acute medical service under an Infectious Diseases Acute Physician (IDP) and other medical teams during one week in 2013 (n=297), and 3 years 2012-2014 (n=47,585). Primary Outcome Measure Antibiotic use in days of therapy (DOT): raw group metrics and regression analysis adjusted for case-mix. Secondary Outcome Measures 30-day all-cause mortality, treatment failure and length of stay. Results Antibiotic use was 173 versus 282 DOT/100 admissions in the IDP vs non-IDP group. Using case-mix adjusted zero-inflated Poisson regression, IDP patients were significantly less likely to receive an antibiotic (adjusted OR=0.25 (95% CI 0.07-0.84), p=0.03) and received shorter courses (adjusted RRR=0.71 (95% CI 0.54-0.93), p=0.01). Clinically stable IDP patients of uncertain diagnosis were more likely to have antibiotics held (87% versus 55%; p=0.02). There was no significant difference in treatment failure or mortality (adjusted p&gt;0.5; also in the three-year dataset), but IDP patients were more likely to be admitted overnight (adjusted OR=3.53 (95% CI 1.24-10.03) p=0.03) and have longer length-of-stay (adjusted RR=1.19 (95% CI 1.05-1.36) p=0.007). Conclusions The IDP-led group used 30% less antibiotic therapy with no adverse clinical outcome, suggesting antibiotic use can be reduced safely in the acute setting. This may be achieved in part by holding antibiotics and admitting the patient for observation rather than prescribing, which has implications for costs and hospital occupancy. More information is needed to indicate whether any such longer admission will increase or decrease risk of antibiotic-resistant infections. </p

Antibiotic use and clinical outcomes in the acute setting under management by an Infectious Diseases Acute Physician versus other clinical teams: a cohort study

Objectives To assess the magnitude of difference in antibiotic use between clinical teams in the acute setting and assess evidence for any adverse consequences to patient safety or healthcare delivery. Design Prospective cohort study (1 week) and analysis of linked electronic health records (3 years). Setting UK tertiary care centre. Participants All patients admitted sequentially to the acute medical service under an Infectious Diseases Acute Physician (IDP) and other medical teams during one week in 2013 (n=297), and 3 years 2012-2014 (n=47,585). Primary Outcome Measure Antibiotic use in days of therapy (DOT): raw group metrics and regression analysis adjusted for case-mix. Secondary Outcome Measures 30-day all-cause mortality, treatment failure and length of stay. Results Antibiotic use was 173 versus 282 DOT/100 admissions in the IDP vs non-IDP group. Using case-mix adjusted zero-inflated Poisson regression, IDP patients were significantly less likely to receive an antibiotic (adjusted OR=0.25 (95% CI 0.07-0.84), p=0.03) and received shorter courses (adjusted RRR=0.71 (95% CI 0.54-0.93), p=0.01). Clinically stable IDP patients of uncertain diagnosis were more likely to have antibiotics held (87% versus 55%; p=0.02). There was no significant difference in treatment failure or mortality (adjusted p>0.5; also in the three-year dataset), but IDP patients were more likely to be admitted overnight (adjusted OR=3.53 (95% CI 1.24-10.03) p=0.03) and have longer length-of-stay (adjusted RR=1.19 (95% CI 1.05-1.36) p=0.007). Conclusions The IDP-led group used 30% less antibiotic therapy with no adverse clinical outcome, suggesting antibiotic use can be reduced safely in the acute setting. This may be achieved in part by holding antibiotics and admitting the patient for observation rather than prescribing, which has implications for costs and hospital occupancy. More information is needed to indicate whether any such longer admission will increase or decrease risk of antibiotic-resistant infections. </p

Reducing the demand for antibiotic prescriptions: evidence from an online survey of the general public on the interaction between preferences, beliefs and information, United Kingdom, 2015

Antimicrobial resistance (AMR), a major public health threat, is strongly associated with human antibiotic consumption. Influenza-like illnesses (ILI) account for substantial inappropriate antibiotic use; patient understanding and expectations probably play an important role. This study investigated what drives patient expectations for antibiotics for ILI; particularly whether AMR-awareness, or risk or time preference, plays a role. In 2015 a representative online panel survey of 2,064 United Kingdom based adults asked respondents about antibiotic usage and effectiveness for ILI. Explanatory variables in multivariable regression included AMR-awareness, risk and time preferences plus covariates. The tendency not to prioritise immediate gain over later reward was independently strongly associated with greater awareness that antibiotics are inappropriate for ILI. Independently, erroneous beliefs and low AMR-awareness significantly predicted reported antibiotic use. However, 272 (39%) of those with low AMR-awareness said the AMR-information we provided would lead them to ask a doctor for antibiotics more often, significantly more than would do so less often, and in contrast to those with high AMR-awareness (p&lt;0.0001). Information campaigns to reduce AMR may risk a paradoxical consequence of actually increasing public demand for antibiotics. Public antibiotic stewardship campaigns should be tested on a small scale before wider adoption.</p

Antimicrobial practice - Safe intravenous antibiotic therapy at home: Experience of a UK based programme

Outpatient iv antibiotic therapy is well developed in the United States, largely because of pressures from third-party payers to reduce costs of medical care. We have developed an outpatient iv antibiotic programme in Oxford, that has evolved from a desire to provide high quality iv therapy to AIDS patients with cytomegalovirus retinitis. We describe the rationale of the service and report on our first two years' experience. We treated 67 consecutive patients (eight with HIV infection) at home with iv antibiotics. This resulted in a saving of 2275 hospital days for those patients without HIV infection. HIV positive patients received 69 months of home iv therapy. Minor intravascular catheter complications occurred in only five patients (7.5%). The only serious complications were three episodes of catheter-related sepsis (4.5%), all occurring in AIDS patients who had lines in for more than six months. We have shown that home iv antibiotic therapy can be delivered safely to patients with a wide variety of infectious problems using the existing network of community nurses in the National Health Service. Essential components to the programme include a multidisciplinary team working between the hospital and community and a written shared care protocol. Such a programme can result in reduced lengths of hospital stay and patient, community nurse and physician satisfaction

Machine learning for classifying tuberculosis drug-resistance from DNA sequencing data

Motivation Correct and rapid determination of Mycobacterium tuberculosis (MTB) resistance against available tuberculosis (TB) drugs is essential for the control and management of TB. Conventional molecular diagnostic test assumes that the presence of any well-studied single nucleotide polymorphisms is sufficient to cause resistance, which yields low sensitivity for resistance classification. Methods Compared to previous rules-based approach, the sensitivities from the best-performing models increased by 2-4% for isoniazid, rifampicin and ethambutol to 97% (P &lt; 0.01), respectively; for ciprofloxacin and multi-drug resistant TB, they increased to 96%. For moxifloxacin and ofloxacin, sensitivities increased by 12 and 15% from 83 and 81% based on existing known resistance alleles to 95% and 96% (P &lt; 0.01), respectively. Particularly, our models improved sensitivities compared to the previous rules-based approach by 15 and 24% to 84 and 87% for pyrazinamide and streptomycin (P &lt; 0.01), respectively. The best-performing models increase the area-under-the-ROC curve by 10% for pyrazinamide and streptomycin (P &lt; 0.01), and 4–8% for other drugs (P &lt; 0.01). Availability and implementation The details of source code are provided at http://www.robots.ox.ac.uk/~davidc/code.php.</p

Naturally mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation

Staphylococcus aureusis a major bacterial pathogen, which causes severe blood and tissue infections that frequently emerge by autoinfection with asymptomatically carried nose and skin populations. However, recent studies report that bloodstream isolates differ systematically from those found in the nose and skin, exhibiting reduced toxicity toward leukocytes. In two patients, an attenuated toxicity bloodstream infection evolved from an asymptomatically carried high-toxicity nasal strain by loss-of-function mutations in the gene encoding the transcription factor repressor of surface proteins (rsp). Here, we report that rsp knockout mutants lead to global transcriptional and proteomic reprofiling, and they exhibit the greatest signal in a genome-wide screen for genes influencing S. aureus survival in human cells. This effect is likely to be mediated in part via SSR42, a long-noncoding RNA. We show that rsp controls SSR42 expression, is induced by hydrogen peroxide, and is required for normal cytotoxicity and hemolytic activity. Rsp inactivation in laboratory- and bacteremia derived mutants attenuates toxin production, but up-regulates other immune subversion proteins and reduces lethality during experimental infection. Crucially, inactivation of rsp preserves bacterial dissemination, because it affects neither formation of deep abscesses in mice nor survival in human blood. Thus, we have identified a spontaneously evolving, attenuated-cytotoxicity, non hemolytic S. aureus phenotype, controlled by a pleiotropic transcriptional regulator/noncoding RNA virulence regulatory system, capable of causing S. aureus bloodstream infections. Such a phenotype could promote deep infection with limited early clinical manifestations, raising concerns that bacterial evolution within the human body may contribute to severe infection