Incidence and risk factors for healthcare utilisation among patients discharged on outpatient parenteral antimicrobial therapy.

Outpatient parenteral antimicrobial therapy (OPAT) programmes facilitate hospital discharge, but patients remain at risk of complications and consequent healthcare utilisation (HCU). Here we elucidated the incidence of and risk factors associated with HCU in OPAT patients. This was a retrospective, single-centre, case-control study of adult patients discharged on OPAT. Cases (n = 63) and controls (n = 126) were patients that did or did not utilise the healthcare system within 60 days. Characteristics associated with HCU in bivariate analysis (P ≤ 0.2) were included in a multivariable logistic regression model. Variables were retained in the final model if they were independently (P < 0.05) associated with 60-day HCU. Among all study patients, the mean age was 55 ± 16, 65% were men, and wound infection (22%) and cellulitis (14%) were common diagnoses. The cumulative incidence of 60-day unplanned HCU was 27% with a disproportionately higher incidence in the first 30 days (21%). A statin at discharge (adjusted odds ratios (aOR) 0.23, 95% confidence intervals (CIs) 0.09-0.57), number of prior admissions in past 12 months (aOR 1.48, 95% CIs 1.05-2.10), and a sepsis diagnosis (aOR 4.62, 95% CIs 1.23-17.3) were independently associated with HCU. HCU was most commonly due to non-infection related complications (44%) and worsening primary infection (31%). There are multiple risk factors for HCU in OPAT patients, and formal OPAT clinics may help to risk stratify and target the highest risk groups.

Pharmacokinetics/pharmacodynamics of antipseudomonal bacteriophage therapy in rats: a proof-of-concept study.

OBJECTIVES: Pan-drug-resistant (PDR) Pseudomonas aeruginosa is one of the three top-priority pathogens identified by the WHO, and bacteriophages have been investigated as an alternative therapy. However, knowledge on the pharmacokinetics/pharmacodynamics (PK/PD) of phage therapy is sparse, limiting its clinical applications. This study aimed to evaluate the PK/PD of the antipseudomonal phage øPEV20 in vivo following intravenous administration. METHODS: Healthy Sprague-Dawley rats were given øPEV20 as a single intravenous bolus of ~6, 9 and 11-log10PFU/rat. Arterial blood was sampled over 72 h. At 72 h, the animals were killed and multiple tissues were harvested for biodistribution studies. A PK model was developed using the importance sampling algorithm and deterministic simulations with a PD model were performed. RESULTS: A three-compartment model with non-linear clearance described the exposure of øPEV20 in blood. Model evaluation indicated that the model was robust and parameter estimates were accurate. The median (standard error) values of model-predicted PK parameters for VC, VP1, VP2, Q1, Q2, Vm and Km were 111 mL/rat (8.5%), 128 mL/rat (4.97%), 180 mL/rat (4.59%), 30.4 mL/h/rat (19.2%), 538 mL/h/rat (4.97%), 4.39 × 1010 PFU/h/rat (10.2%) and 1.64 × 107 PFU/mL/rat (3.6%), respectively. The distribution of øPEV20 was not homogeneous; there was preferential accumulation in the liver and spleen. Deterministic simulations with a PD model confirmed the importance of the host immune system in facilitating phage-mediated bacterial elimination. CONCLUSIONS: We developed a robust PK model to describe the disposition of phages in healthy rats. This model may have significant potential in facilitating future preclinical and clinical PK/PD investigations.

Assessment and modelling of antibacterial combination regimens.

BACKGROUND: The increasing global prevalence of multidrug-resistant bacteria is forcing clinicians to prescribe combination antibiotic regimens to treat serious infections. Currently, the joint activity of a combination is quantified by comparing the observed and expected effects using a reference model. These reference models make different assumptions and interpretations of synergy. They fail to: (i) account for multiple bacterial subpopulations with differing susceptibilities; (ii) quantify or interpret the explicit interaction (synergy/antagonism) mechanisms; and (iii) accommodate spontaneous mutations. AIMS: To develop better study designs, mathematical models, metrics and pharmacodynamic analyses to assist with the identification of highly active combinations that are translatable to the clinical context to address the mounting antibiotic resistance threat. SOURCES: PubMed, references of identified studies and reviews, and personal experience when evidence was lacking. CONTENT: We reviewed metrics and approaches for quantifying the joint activity of the combination. The first example is using experimental data from an in vitro checkerboard synergy panel to develop and illustrate a less model-dependent method for assessing combination regimens. In the second example a pharmacokinetic/pharmacodynamic model was developed using mechanism-based mathematical modelling and monotherapy and combination therapy data obtained from an in vitro hollow fibre infection model evaluating linezolid and rifampin regimens against Mycobacterium tuberculosis. IMPLICATIONS: Mechanism-based mathematical approach provides an excellent platform for describing the time course of effect while taking into account the mechanisms of different antibiotics and differing pathogen susceptibilities. This approach allows for the future integration of 'omics' data describing host-pathogen interactions, that will provide a systems-level understanding of the underlying infectious process, and enable the design of effective combination therapies.

Post-surgical mediastinitis due to carbapenem-resistant Enterobacteriaceae: Clinical, epidemiological and survival characteristics.

Invasive infections due to carbapenem-resistant Enterobacteriaceae (CRE), including polymyxin-resistant (PR-CRE) strains, are being increasingly reported. However, there is a lack of clinical data for several life-threatening infections. Here we describe a cohort of patients with post-surgical mediastinitis due to CRE, including PR-CRE. This study was a retrospective cohort design at a single cardiology centre. Patients with mediastinitis due to CRE were identified and were investigated for clinically relevant variables. Infecting isolates were studied using molecular techniques. Patients infected with polymyxin-susceptible CRE (PS-CRE) strains were compared with those infected with PR-CRE strains. In total, 33 patients with CRE mediastinitis were studied, including 15 patients (45%) with PR-CRE. The majority (61%) were previously colonised. All infecting isolates carried blaKPC genes. Baseline characteristics of patients with PR-CRE mediastinitis were comparable with those with PS-CRE mediastinitis. Of the patients studied, 70% received at least one agent considered active in vitro and most patients received at least three concomitant antibiotics. Carbapenem plus polymyxin B was the most common antibiotic combination (73%). Over 90% of patients underwent surgical debridement. Overall, in-hospital mortality was 33% and tended to be higher in patients infected with PR-CRE (17% vs. 53%; P=0.06). In conclusion, mediastinitis due to CRE, including PR-CRE, can become a significant challenge in centres with CRE and a high cardiac surgery volume. Despite complex antibiotic treatments and aggressive surgical procedures, these patients have a high mortality, particularly those infected with PR-CRE.

Risk factors for the spread of antibiotic-resistant bacteria.

The emergence of antibiotic resistance is primarily due to excessive and often unnecessary use of antibiotics in humans and animals. Risk factors for the spread of resistant bacteria in hospitals and the community can be summarised as over-crowding, lapses in hygiene or poor infection control practices. Increasing antibiotic resistance in bacteria has been exacerbated by the slow pace in developing newer antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and multiresistant Gram-negative bacteria are spread primarily by direct or indirect person-to-person contact. Independent risk factors for MRSA include the use of broad spectrum antibiotics, the presence of decubitus ulcers and prosthetic devices while those for VRE include prolonged hospitalisation and treatment with glycopeptides or broad spectrum antibiotics. For the spread of resistant Gram-negative bacteria risk factors include urinary catheterisation, excessive use of antibiotics and contamination of humidifiers and nebulisers. The spread of penicillin-resistant pneumococci (PRP) and drug-resistant and multidrug-resistant tuberculosis (MDRTb) is due to airborne transmission. Risk factors for the spread of PRP include overcrowding, tracheostomies and excessive use of penicillins for viral respiratory infections; for MDRTb they include poor compliance, convergence of immunosuppressed patients, delayed diagnosis or treatment, and poor or inadequate ventilation and isolation facilities. Recent developments in the genomic mapping of many bacteria and advances in combinatorial chemistry promise to usher in a new era of antibiotic development. While this may result in our regaining some of the ground lost to resistant bacteria, there will still be a continuing need to minimise the spread of antibiotic resistance through the rational use of antibiotic agents and stringent infection control practice.

Control of outbreaks of viral diarrhoea in hospitals--a practical approach.

Outbreaks of viral diarrhoea are common in hospitals, particularly in the geriatric and children's wards. Person-to-person spread is the most frequent mode of transmission of infection. Establishment of alerting mechanisms, liaison with laboratories with electron microscopy facilities for making the diagnosis, isolation of patients, use of appropriate disinfectants and maintaining good lines of communication are all important for successful control of these outbreaks.

A review of hospitalized patients with bacterial gastroenteritis.

The distribution and clinical management of thirty-two hospitalized patients with salmonella and campylobacter infections were reviewed and the impact of these infections on hospital resources was assessed. Eighteen patients with salmonella infection had an age and sex distribution comparable with the community cases. In contrast, 10 out of 14 (71.4%) patients with campylobacter infection were under 20 years of age though the peak incidence of the infection in the community occurred in the 21-65 years age group (67%). There was no male predominance. The median duration of stay in hospital was 6 days for patients with salmonella infection and 3 days for those with campylobacter infection. Physicians were inconsistent in the treatment of campylobacter infection. Overall the financial impact of managing patients with salmonella and campylobacter infection was considerable (1384 pounds and 779 pounds respectively per patient). A limitation on unnecessarily prolonged hospital stays and the establishment of clear guidelines for the clinical management of these infections are necessary.

Conventional screening for enteropathogenic Escherichia coli in the UK. Is it appropriate or necessary?

Enteropathogenic Escherichia coli (EPEC) is a well-recognized cause of infantile diarrhoea in the developing countries. In the developed countries, however, the incidence of EPEC associated outbreaks has dramatically declined. The last major outbreak in the UK was reported in 1980. This paper reviews the recent advances in the field of pathogenesis of diarrhoea caused by EPEC and questions the need to screen routinely for EPEC by conventional serological methods used in clinical microbiology laboratories in the UK.

Vancomycin-resistant gram-positive cocci: risk factors for faecal carriage.

This case-control study was undertaken to identify the risk factors for the gastrointestinal carriage of vancomycin-resistant, Gram-positive cocci (VRGPC) including vancomycin-resistant enterococci (VRE). Use of oral vancomycin (P = 0.003) or cephalosporins (P = 0.03) and prolonged duration of stay in the hospital (P = 0.02) were found to be the significant risk factors. Other previously suggested risk factors such as location of the patients and presence of central venous or arterial lines were not significantly associated with carriage of VRGPC. Judicious usage of glycopeptides (particularly oral vancomycin) and cephalosporins is likely to be the most effective way to prevent and control the spread of VRGPC and VRE.

Routine cleaning and the elimination of Campylobacter pylori from endoscopic biopsy forceps.

The effect of routine cleaning in removing Campylobacter pylori from the biopsy forceps of endoscopes has been examined in a series of 50 patients. Campylobacter pylori was isolated from the biopsies of 15 of the patients, while one of the 50 biopsy forceps washings yielded the organism after routine cleaning. This study suggests that there is a small chance of transmitting C. pylori by endoscopic equipment if cleaning is the only method of decontamination adopted.

Ciprofloxacin as a cause of Clostridium difficile-associated diarrhoea in an HIV antibody-positive patient.

Ciprofloxacin is an uncommon cause of pseudomembranous colitis. A case is described in which diarrhoea was associated with the presence of clostridial toxin in an HIV-infected patient and the possible implications are discussed.

Potassium dichromate as an oxidimetric reagent.

A critical and historical review is made of the use of potassium dichromate in oxidimetry.

Aqueous acetic acid as a medium for the facile use of ferroin as redox indicator in the presence of perchloric acid.

Ferroin cannot be used as an indicator in perchloric acid medium because of precipitation of ferroin perchlorate. There is no precipitation, however, if the solution contains 30%(v/v) of acetic acid.

Some triphenylmethane dyes as redox indicators in the titration of antimony(III) with cerium(IV) sulphate.

Erioglaucine A, Eriogreen B, Patent Blue and Xylene Cyanol FF work satisfactorily for the titration of Sb(III) with Ce(IV) in 1-2N sulphuric acid medium with iodine as catalyst. In hydrochloric acid medium the colour of the oxidized dye is very evanescent but is very much improved in intensity and stability by the addition of manganese(II) sulphate; no catalyst is needed.

A new oxidimetric reagent-potassium dichromate in a strong phosphoric acid medium-VIII Potentiometric titration of molybdenum(VI) and vanadium(V).

A new titrimetric method is described for the determination of molybdenum(VI) involving prior reduction to Mo(V) with an excess of Fe(II) in a concentrated phosphoric acid solution, followed by titration with dichromate. The titration can be done at room temperature and without protective atmosphere. Uranium interferes, but vanadium may be determined simultaneously.

A new oxidimetric reagent: potassium dichromate in a strong phosphoric acid medium--VII. Photometric titration of vanadium(IV) and of cerium(III) alone and in mixtures with iroN(II).

Vanadium(IV) can be accurately titrated with potassium dichromate in media containing phosphoric acid of 3-12M concentration: the change in absorption of vanadium(IV) is followed in the region 660 mmicro using a red filter. It is more convenient to carry out the titration in 3M phosphoric acid because at higher concentrations chloride, nitrate, cerium(III) and manganese(II) may interfere. Photoelcetric titration is more convenient than potentiometric because the former can be made in a 3M phosphoric acid medium, whereas the latter is possible only in 12M phosphoric acid. The simultaneous differential photometric titration of iron(II) and vanadium(IV) is also possible. Conditions have been found for the photometric titration of cerium(III) and of cerium(III) plus iron(II). The titration is carried out (at 450 mmicro or with a blue filter) in about 10.5M phosphoric acid. Application of the method to a cerium mineral is considered.

Oxidimetric determination of indigo with iron(III) and hexacyanoferrate(III).

The use of iron(III) in sulphuric acid medium and of potassium hexacyanoferrate(III) in hydrochloric acid medium has been investigated for the oxidimetric determination of indigo and indigo sulphonic acid. Conditions have been established for the assay of the dye with iron(III) sulphate at 100 degrees and with potassium hexacyanoferrate(III) at room temperature.

A new oxidimetric reagent: potassium dichromate in a strong phosphoric acid medium-VI Potentiometric titration of vanadium(III) alone and in mixture with vanadium(IV).

Vanadium(III) can be titrated at room temperature with potassium dichromate in an 8-12M phosphoric acid medium. Two potential breaks are observed in 12M phosphoric add with 0.2N potassium dichromate, the first corresponding to the oxidation of vanadium(III) to vanadium(IV) and the second to the oxidation of vanadium(IV) to vanadium(V). In titrations with 0.05N dichromate only the first break in potential is clearly observed. The method has been extended to the titration of mixtures of vanadium(III) and vanadium(IV). Conditions have also been found for the visual titration of vanadium(III) using ferroln or barium diphenylamine sulphonate as indicator.

Titrimetric determination of vanadium(IV) with cerium (IV)sulphate at room temperature using ferroin as indicator.

A procedure has been developed for the visual titrimetric determination of vanadium(IV) with cerium(IV) sulphate, using ferroin is redox indicator. The method has been extended to the determination of iron(II) and vanadium(IV) in mixtures.

Stoichiometry of the reaction between iron(II) and chromium(VI).

The suitability of potassium dichromate as a standard oxidant has been examined by comparing direct oxidation of iron(II) solutions with alternative back-titration procedures.