Complicated skin and soft tissue infections: literature review of evidence for and experience with daptomycin

Skin and soft tissue infections (SSTIs) are the second most common infection encountered in hospitals. Management decisions have become increasingly complex due to the prevalence of resistant pathogens, the wide array of licensed antimicrobials and the availability of potent oral agents and of out-patient parenteral antibiotic therapy. Daptomycin is one of the newer therapeutic agents licensed for complex SSTI management. Rapid cidality, good soft tissue penetration, once daily IV bolus administration and activity against resistant Gram-positive infections make daptomycin an attractive option both in hospitalized and community treated patients. A comprehensive review of the evidence for and experience with daptomycin and its use in SSTIs is presented

Restrictive antibiotic stewardship associated with reduced hospital mortality in gram-negative infection

Introduction: Antimicrobial stewardship has an important role in the control of Clostridium difficile infection (CDI) and antibiotic resistance. An important component of UK stewardship interventions is the restriction of broad-spectrum beta-lactam antibiotics and promotion of agents associated with a lower risk of CDI such as gentamicin. Whilst the introduction of restrictive antibiotic guidance has been associated with improvements in CDI and antimicrobial resistance evidence of the effect on outcome following severe infection is lacking. Methods: In 2008, Glasgow hospitals introduced a restrictive antibiotic guideline. A retrospective before/after study assessed outcome following gram-negative bacteraemia in the 2-year period around implementation. Results: Introduction of restrictive antibiotic guidelines was associated with a reduction in utilisation of ceftriaxone and co-amoxiclav and an increase in amoxicillin and gentamicin. 1593 episodes of bacteraemia were included in the study. The mortality over 1 year following gram-negative bacteraemia was lower in the period following guideline implementation (RR 0.852, P = 0.045). There was no evidence of a difference in secondary outcomes including ITU admission, length of stay, readmission, recurrence of bacteraemia and need for renal replacement therapy. There was a fall in CDI (RR 0.571, P = 0.014) and a reduction in bacterial resistance to ceftriaxone and co-amoxiclav but no evidence of an increase in gentamicin resistance after guideline implementation. Conclusion: Restrictive antibiotic guidelines were associated with a reduction in CDI and bacterial resistance but no evidence of adverse outcomes following gram-negative bacteraemia. There was a small reduction in one year mortality

Associations Between Declining Antibiotic Use in Primary Care in Scotland and Hospitalisation with Infection and Patient Satisfaction:Longitudinal Population Study

BACKGROUND: Reducing antibiotic use is central to antimicrobial stewardship, but may have unintended consequences. OBJECTIVES: To examine associations between size of decline in antibiotic prescriptions in general practices and (i) rate of hospitalization for infection and (ii) patient satisfaction. METHODS: Routine data analysis for all general practices in Scotland, quarter one 2012 (Q1 2012) to quarter one 2018 (Q1 2018). Practices were grouped into quartiles of rate of change in prescribing and changes in rates of hospitalization were compared across groups. For satisfaction analysis, associations between practice-level patient satisfaction in 2017–18 (Scottish Health and Care Experience Survey) and prior change in antibiotic prescription were examined. RESULTS: Antibiotic prescriptions overall fell from 194.1 prescriptions/1000 patients in Q1 2012 to 165.3 in Q1 2018 (14.9% reduction). The first quartile of practices had a non-significant increase in prescriptions [change per quarter = 0.22 (95% CI −0.42 to 0.86) prescriptions/1000 patients], compared with large reductions in the other three groups, largest in quartile four: −2.95 (95% CI −3.66 to −2.24) prescriptions/1000 patients/quarter (29.7% reduction overall). In all quartiles, hospitalizations with infection increased. The increase was smallest in quartile four (the biggest reduction in prescriptions) and highest in quartile one (no significant change in prescriptions): 2.18 (95% CI 1.18 to 3.19) versus 3.68 (95% CI 2.64 to 4.73) admissions/100 000 patients/quarter, respectively [difference = − 1.50 (95% CI −2.91 to −0.10)]. There was no statistically significant association between change in antibiotic prescriptions and patient satisfaction. CONCLUSIONS: Very large reductions in antibiotic prescriptions in Scottish general practices have not been associated with increases in hospitalization with infection or changes in patient satisfaction

Indications for the use of metronidazole in the treatment of non-periodontal dental infections: a systematic review

Background: Dental practitioners are the largest prescribers of metronidazole. Antibiotics should only be prescribed when systemic involvement is clear and should be limited to monotherapy with β-lactams in the first instance. Objectives: To determine whether metronidazole used as monotherapy or in addition to a β-lactam antibiotic offers any additional benefit over β-lactam monotherapy in non-periodontal dental infections. Methods: Searches of Ovid Medline, Ovid Embase, Cochrane library and trials registries, forward and backward citations, for studies published between database inception and 2 August 2021. All randomized clinical trials (RCTs) and non-randomized trials comparing either systemic metronidazole monotherapy or metronidazole combined with a β-lactam with β-lactam monotherapy for the treatment of non-periodontal dental infections in adults or children in outpatient settings were included. Results: Four publications reporting three RCTs comparing metronidazole with a β-lactam antibiotic were recovered. Studies were conducted in the 1970s–80s and aimed to demonstrate metronidazole was as effective as penicillin for the treatment of acute pericoronitis or acute apical infections with systemic involvement. Meta-analysis of results was not possible due to differences in measurement of infection signs. All studies concluded that metronidazole and penicillin are equally effective for the treatment of non-periodontal dental infections with systemic involvement. Conclusions: Metronidazole does not provide superior clinical outcomes (alone or in combination with a β-lactam) when compared with a β-lactam antibiotic alone for the treatment of non-periodontal dental infections in general dental practice. Guidelines should reinforce the importance of surgical interventions and if appropriate the use of a single agent narrow-spectrum β-lactam

Photoperiodic control of the <i>Arabidopsis</i> proteome reveals a translational coincidence mechanism

Plants respond to seasonal cues such as the photoperiod, to adapt to current conditions and to prepare for environmental changes in the season to come. To assess photoperiodic responses at the protein level, we quantified the proteome of the model plant Arabidopsis thaliana by mass spectrometry across four photoperiods. This revealed coordinated changes of abundance in proteins of photosynthesis, primary and secondary metabolism, including pigment biosynthesis, consistent with higher metabolic activity in long photoperiods. Higher translation rates in the day than the night likely contribute to these changes, via an interaction with rhythmic changes in RNA abundance. Photoperiodic control of protein levels might be greatest only if high translation rates coincide with high transcript levels in some photoperiods. We term this proposed mechanism “translational coincidence”, mathematically model its components, and demonstrate its effect on the Arabidopsis proteome. Datasets from a green alga and a cyanobacterium suggest that translational coincidence contributes to seasonal control of the proteome in many phototrophic organisms. This may explain why many transcripts but not their cognate proteins exhibit diurnal rhythms

Evidence For A Precessing Accretion Disk in the Nucleus of NGC 1097

We present new spectroscopic observations of the LINER (and now Seyfert 1) nucleus of NGC 1097, and discuss the evolution of its broad, double-peaked Balmer lines. When originally discovered in 1991, the red peak of the double-peaked H-alpha line was stronger than the blue, while by 1994 the H-alpha profile had become almost symmetric and the integrated line flux had decreased to half its original value. Our new spectrum, taken in 1996, shows that the broad, double-peaked lines have returned to almost their original strengths, the profiles of H-beta and H-alpha are identical to within errors, and the broad-line emitting region is unreddened. However, the profile of the Balmer lines is now such that the blue peak is stronger than the red, opposite to the asymmetry observed in 1991. Various models are considered for the observed behavior, all assuming that the emission lines originate in an accretion disk. We present a refined version of the precessing, planar, elliptical accretion ring model proposed by Storchi-Bergmann et al. and Eracleous et al. This model provides an acceptable fit to the line profiles. We also consider the possibility that the line profile evolution results from a precessing warp in the disk, induced by irradiation from the center, and show that the range of radii and precession time scales expected in this model are consistent with the observations. The sudden appearance of the "disk-like" broad line profiles in NGC 1097 could have resulted from the formation of a new accretion disk due to, for example, the tidal disruption of a star, or the illumination of a pre-existing disk by a transient ionizing source at the center of the disk.Comment: Accepted for publication in the Astrophysical Journal. TeX file with 5 postscript figures embeded using psfig.tex, 13 page

Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis.

Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey's visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM

Antimicrobial point prevalence surveys in two Ghanaian hospitals : opportunities for antimicrobial stewardship

Background: Improved knowledge regarding antimicrobial use in Ghana is urgently needed to reduce antimicrobial resistance (AMR). This includes point prevalence studies (PPS) in hospitals. Objectives were: (i) provide baseline data in two hospitals (Keta Municipal Hospital – KMH and Ghana Police Hospital – GPH) and identify priorities for improvement; (ii) assess the feasibility of conducting PPS; (iii) compare results with others. Methods: Standard PPS design using the Global PPS paper forms, subsequently transferred to their template. Training undertaken by the Scottish team. Quality indicators included rationale for use; stop and review dates, and guideline compliance. Results: Prevalence of antibiotic use was 65.0% in GPH and 82.0% in KMH. Penicillins and other beta-lactam antibiotics were the most prescribed in both hospitals, with third generation cephalosporins mainly used in GPH. Antibiotic treatment was mainly empirical and commonly administered intravenously (IV), duration was generally short with timely oral switching, and infections were mainly community acquired. Encouragingly, good documentation of the indications for antibiotic use in both hospitals and 50.0-66.0% guideline compliance (although for many indications no guideline existed). In addition, almost all prescribed antibiotics had stop dates and there appeared no missed doses. The duration of use for surgical prophylaxis was generally more than one day (69.0% in GPH and 77.0% in KMH). Conclusions: These two hospitals were the first in Ghana to use the Global PPS system. We found the PPS was feasible and relatively rapid, achieved with limited training. Targets for improvement identified included broad-spectrum antibiotics, duration of treatment and high empiric use

Expert Opinion on Dose Regimen and Therapeutic Drug Monitoring for Long-Term Use of Dalbavancin: Expert Review Panel

Background: Dalbavancin is a lipoglycopeptide with a long elimination half-life, currently licensed for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults. Dalbavancin's potential in treating off-label complex gram-positive infections is promising and real-world experience in treating such infections is growing. However, clear guidance on extended dosing regimens is lacking. Objectives: We aim to provide clear expert opinion based on recent pharmacokinetic literature and expert and real-world experience in infection areas that require &gt;2 weeks of treatment. Methods: A single face-to-face meeting was held in September 2022 to collate expert opinion and present safety data of dalbavancin use in these clinical indications. A survey was completed by all authors on their individual experience with dalbavancin which highlighted the heterogeneity in the regimens used. Results: After review of the survey data and recent literature, we present expert panel proposals which accommodate different healthcare settings and resource availability, and centre around the length of treatment duration including up to, or exceeding, 6 weeks. To achieve adequate dalbavancin concentrations for up to 6 weeks, 3,000mg of dalbavancin should be given over 4 weeks for the agreed complex infections requiring &gt;2 weeks treatment. Therapeutic drug monitoring (TDM) is advised for longer treatment durations and in case of renal failure. Specific dosing recommendations for other special populations require further investigation. Conclusions: These proposals based on expert opinion have been defined to encourage best practice with dalbavancin to optimise its administration beyond the current approved licenced dose across different healthcare settings

Supporting global antimicrobial stewardship : antibiotic prophylaxis for the prevention of surgical site infection in low and middle income countries (LMICs): a scoping review and meta-analysis

Background: The Scottish Antimicrobial Prescribing Group (SAPG) is supporting two hospitals in Ghana to develop antimicrobial stewardship. Early intelligence gathering suggested that surgical prophylaxis was suboptimal. We reviewed the evidence for use of surgical prophylaxis to prevent surgical site infections (SSI) in low and middle-income countries (LMICs) to inform this work. Methods: MEDLINE, Embase, Cochrane, CINHAL and Google Scholar were searched from inception to 17 February, 2020 for trials, audits, guidelines and systematic reviews in English. Grey literature, websites and reference lists of included studies were searched. Randomised clinical trials reporting incidence of SSI following Caesarian section were included in two meta-analyses. Narrative analysis of studies that explored behaviours and attitudes was conducted. Results: This review included 51 studies related to SSI and timing of antibiotic prophylaxis in LMICs. Incidence of SSIs is higher in LMICs, infection surveillance data is poor and there is a lack of local guidelines for antibiotic prophylaxis. Education to improve appropriate antibiotic prophylaxis is associated with reduction of SSI in LMICs.The random effects pooled mean risk ratio of SSI in Caesarian section was 0.77 (95% CI: 0.51 to 1.17) for pre-incision versus post-incision prophylaxis and 0.89 (95% CI: 0.55 to 1.14) for short versus long duration, Reduction in cost and nurse time was reported in shorter duration SAP. Conclusion: There is scope for improvement but interventions must include local context and address strongly held beliefs. Establishment of local multidisciplinary teams will promote ownership and sustainability of change