Robert Townsend

Antibiotic stewardship and early discharge from hospital: impact of a structured approach to antimicrobial management

OBJECTIVES To assess the impact of an infection team review of patients receiving antibiotics in six hospitals across the UK and to establish the suitability of these patients for continued care in the community. METHODS An evaluation audit tool was used to assess all patients on antibiotic treatment on acute wards on a given day. Clinical and antibiotic use data were collected by an infection team (doctor, nurse and antibiotic pharmacist). Assessments were made of the requirement for continuing antibiotic treatment, route and duration [including intravenous (iv)/oral switch] and of the suitability of the patients for discharge from hospital and their requirement for community support. RESULTS Of 1356 patients reviewed, 429 (32%) were on systemic antibiotics, comprising 165 (38%) on iv ± oral antibiotics and 264 (62%) on oral antibiotics alone. Ninety-nine (23%) patients (including 26 on iv antibiotics) had their antibiotics stopped immediately on clinical grounds. The other 330 (77%) patients (including 139 on iv antibiotics) needed to continue antibiotics, although 47 (34%) could be switched to oral. Eighty-nine (21%) patients were considered eligible for discharge, comprising 10 who would have required outpatient parenteral antibiotic therapy (OPAT), 55 who were suitable for oral outpatient treatment and 24 who had their antibiotics stopped. CONCLUSIONS Infection team review had a significant impact on antimicrobial use, facilitating iv to oral switch and a reduction in the volume of antibiotic use, possibly reducing the risk of healthcare-associated complications and infections. It identified many patients who could potentially have been managed in the community with appropriate resources, saving 481 bed-days. The health economics are reported in a companion paper.

Invasion by Neisseria meningitidis varies widely between clones and among nasopharyngeal mucosae derived from adult human hosts.

Colonization of the human nasopharynx is a feature of some species of Neisseria, and is a prerequisite of invasive meningococcal disease. The likelihood of colonization by Neisseria meningitidis varies widely between humans, and very few develop invasive disease. Explants of nasal mucosa derived from adult patients with non-allergic nasal obstruction were infected experimentally with Neisseria spp. At intervals over 18 h incubation, washed explants were homogenized, and viable bacteria were counted. To estimate bacterial invasion of mucosa, explants were exposed to 0.25% sodium taurocholate for 30 s prior to homogenization. N. meningitidis was recovered from the mucosa and the organism invaded and replicated within the tissue, in contrast to N. lactamica and N. animalis (n=9, P<0.008). N. meningitidis isolates of clones ET-5, ET-37 and lineage III were recovered from and invaded tissue, but strains of clones A4, A:subgroup I, A:subgroup III and A:subgroup IV-1 did not invade (n=6). To measure host variation, survival of N. meningitidis within nasal mucosa of 40 different human donors was measured. Intra-class correlation of replicates was 0.97, but the coefficient of variation of recovered viable counts was 1335% after 4 h and 77% after 18 h incubation. It is concluded that the distinctive colonization and disease potential of Neisseria spp. may be partly a consequence of their ability to invade and survive within human nasopharyngeal mucosa, but that this is influenced greatly by genetic or environmental factors operating on the host mucosa. This is consistent with the unpredictable epidemiology of meningococcal disease.

Fatal necrotizing fasciitis caused by Haemophilus influenzae serotype f.

We describe a case of fatal lower limb necrotizing fasciitis in a 65-year-old man who was treated with broad-spectrum antibiotics, limb amputation and tissue debridement. The causative organism was identified by PCR as Haemophilus influenzae serotype f, which is a highly unusual cause of necrotizing fasciitis.

Evaluation of ChloraPrep (2% chlorhexidine gluconate in 70% isopropyl alcohol) for skin antisepsis in preparation for blood culture collection

OBJECTIVES Blood culture contamination is a significant adverse event. This study evaluated whether using ChloraPrep (2% alcoholic chlorhexidine) instead of 70% isopropyl alcohol wipes reduced contamination rates on two Medical Assessment Units (MAU1 and MAU2). METHODS ChloraPrep was introduced for 2 to 3-month intervention periods, initially on MAU1 and MAU2 and subsequently on MAU1 only. Contamination rates were compared with a matched time period in the preceding year and the three month period before ChloraPrep introduction. Education regarding venepucture technique was delivered. RESULTS Contamination rates for the time matched pre-intervention period were 17.3% (51/295), MAU1 and 13.5% (31/230), MAU2. During the initial period of ChloraPrep use, rates declined (MAU1; 6.6% [P<0.001], MAU2; 8.5% [P=0.11] both Fishers Exact Test). However, rates had already started to fall prior to ChloraPrep introduction. There was a non-significant difference between contamination rates in the comparator period immediately prior to ChloraPrep introduction and rates during the first intervention period (MAU1 and MAU2; P>0.05). During the second intervention period, absence of ChloraPrep on MAU2 did not significantly affect contamination (P=0.41) on this ward. CONCLUSIONS ChloraPrep skin antisepsis did not give a significant reduction in blood culture contamination, but education may have led to the trend to lower contamination.

Haemophilus parainfluenzae prosthetic joint infection. The importance of accurate microbiological diagnosis and options for management.

Figure 1 Intra-operative photograph during 1st stage showing radical soft tissue debridement and excision of sinus. We read with interest the article by Cataldo et al. Here we report a recent case of prosthetic joint infection with an unusual organism treated successfully with minimal systemic antibiotics. A 75 year old male patient with a history of chronic lymphoid leukaemia (currently in remission) underwent a right total knee replacement for osteoarthritis at a district general hospital. Three weeks after discharge he was readmitted with a leaking wound and feeling unwell. He was subsequently taken to theatre for debridement and lavage of the right knee with retention of the prosthesis. Both fluid and one tissue sample from surgery grew Haemophilus Parainfluenzae, sensitive to amoxicillin and resistant to clarythromycin and tetracycline. The patient was treated with flucloxacillin and rifampicin for 6 weeks. Initially the patient’s general condition and knee improved. However, on stopping the antibiotics, he developed an abscess. This was aspirated and a Gram film revealed pus cells but no organisms were seen, nor subsequently cultured. The same antibiotic regime was then reinstated. One month later the patient was seen in our tertiary referral hospital by a consultant specialising in revision arthroplasty surgery. Examination revealed a discharging sinus in the proximal aspect of the wound and movements of the right knee were restricted. The CRP was 46 mg/L and ESR 82 mm/h. No organisms were cultured from a knee aspirate despite antibiotics having been stopped more than 2 weeks prior. A radical debridement with removal of the prosthesis (Fig. 1) was performed and tissue samples were sent to microbiology laboratory. The knee was stabilised with an intra-medullary rod which had been covered with antibiotic loaded bone cement. An additional 1 g of gentamicin and 2 g of vancomycin was added to each mix of Palacos cement (Heraeus Medical, Germany). Home made chains of antibiotic loaded beads with the same antibiotic combination were placed in the suprapatella pouch and both parapatellar gutters. The patient received standard prophylactic antibiotics which consisted of 3 doses of cefuroxime (750 mg). He received no further systemic antibiotics. His post operative recovery was uneventful.

Temocillin: a new candidate antibiotic for local antimicrobial delivery in orthopaedic surgery?

OBJECTIVES To assess the performance of the Gram-negative-specific antibiotic temocillin in polymethylmethacrylate bone cement pre-loaded with gentamicin, as a strategy for local antibiotic delivery. METHODS Temocillin was added at varying concentrations to commercial gentamicin-loaded bone cement. The elution of the antibiotic from cement samples over a 2 week period was quantified by LC-MS. The eluted temocillin was purified by fast protein liquid chromatography and the MICs for a number of antibiotic-resistant Escherichia coli were determined. The impact strength of antibiotic-loaded samples was determined using a Charpy-type impact testing apparatus. RESULTS LC-MS data showed temocillin eluted to clinically significant concentrations within 1 h in this laboratory system and the eluted temocillin retained antimicrobial activity against all organisms tested. Impact strength analysis showed no significant difference between cement samples with or without temocillin. CONCLUSIONS Temocillin can be added to bone cement and retains its antimicrobial activity after elution. The addition of up to 10% temocillin did not affect the impact strength of the cement. The results show that temocillin is a promising candidate for use in antibiotic-loaded bone cement.

Contrasting Effects of Physical Wear on Elution of Two Antibiotics from Orthopedic Cement

ABSTRACT The use of antibiotics as a supplement to bone cement for the purposes of providing a local release of antibiotics is common practice in arthroplasty surgery and the kinetics of elution of the antibiotics in such systems have been investigated previously. However, in these previous studies no account was taken of the potential effects that wear may have on the elution kinetics of the antibiotic. Here, we have modified an existing wear testing rig to allow the simultaneous study of the elution kinetics of bone cement samples containing antibiotics being subjected to immersion only and immersion and conjoint wear. The results show contrasting effects with two commonly used antibiotics. Bone cement containing daptomycin showed no substantial change in antibiotic elution due to wear, while cement containing gentamicin (the most commonly used antibiotic in this application) in contrast demonstrated a substantial reduction in the rate of antibiotic elution when wear was applied. Scanning electron microscopy revealed a possible explanation for these diverse results, due to wear-induced “sealing” of the surface in conjunction with the crystal morphology of the antibiotic.

Analysis of linezolid and tigecycline as candidates for local prophylaxis via antibiotic-loaded bone cement

Objectives To assess the Gram-positive-specific antibiotic linezolid and the broad-spectrum antibiotic tigecycline for use in local antibiotic delivery via antibiotic-loaded bone cement. Methods Linezolid and tigecycline were added to Biomet bone cement at varying concentrations. Antibiotic elution over 1 week was quantified by HPLC-MS. The effect of wear on elution over 51 h was determined using a modified TE-66 wear tester. Eluted antibiotics were used to determine the MICs for a panel of clinically relevant bacteria. The impact strength of antibiotic-loaded samples was determined using a Charpy-type impact testing apparatus. Cytotoxicity of eluted antibiotics against MG-63 cells was evaluated using an MTT assay. Results Linezolid and tigecycline eluted from bone cement to clinically relevant levels within 1 h and retained activity over 1 week. Mechanical wear significantly reduced elution of tigecycline, but had little effect on elution of linezolid. Linezolid showed low cytotoxicity towards MG-63 cells with ⩽300 mg/mL resulting in >50% cell activity. Cytotoxicity of tigecycline was higher, with an IC50 of 5–10 mg/L. Conclusions Linezolid and tigecycline retain activity after elution from bone cement. The concentration of tigecycline may need to be carefully controlled due to cytotoxicity. The effect of wear on bone cement may need to be considered if tigecycline is to be used for local delivery. Up to 10% linezolid can be added without affecting the impact strength of the bone cement. These results are promising indications for future investigation of these antibiotics for use in local antibiotic delivery strategies.

Low-grade infections in nonarthroplasty shoulder surgery

BACKGROUND Recent studies have identified the diagnostic challenge of low-grade infections after shoulder arthroplasty surgery. Infections after nonarthroplasty procedures have not been reported. This study assessed patient-related risk factors, outcomes, and clinical presentation of low-grade infection after open and arthroscopic nonarthroplasty shoulder surgery. METHODS The cases of 35 patients presenting with suspected low-grade infection were reviewed. Biopsy specimens taken at revision surgery were cultured in the sterile environment of a class II laminar flow cabinet and incubated for a minimum of 14 days at a specialist orthopedic microbiology laboratory. Patient-related factors (age, occupation, injection), index surgery, and infection characteristics (onset of symptoms, duration to diagnosis, treatment) were analyzed. RESULTS Positive cultures were identified in 21 cases (60.0%), of which 15 were male patients (71%). Of all patients with low-grade infection, 47.6% were male patients between 16 and 35 years of age. Propionibacterium acnes and coagulase-negative staphylococcus were the most common organisms isolated (81.1% [n = 17] and 23.8% [n = 5], respectively). Of 14 negative culture cases, 9 were treated with early empirical antibiotics (64.3%); 7 patients reported symptomatic improvement (77.8%). Of 5 patients treated with late empirical antibiotics, 4 stated improvement. Patients presented with symptoms akin to resistant postoperative frozen shoulder (persistent pain and stiffness, unresponsive to usual treatments). CONCLUSION Young male patients are at greatest risk for low-grade infections after arthroscopic and open nonarthroplasty shoulder surgery. P. acnes was the most prevalent organism. Patients presented with classic postoperative frozen shoulder symptoms, resistant to usual treatments. Interestingly, 78.6% of patients with negative cultures responded positively to empirical treatment.

Evaluation of an agar-gradient minimum-inhibitory-concentration method (the Etest) as a rapid and direct measure of antimicrobial susceptibility in Gram-negative bacteraemia

BACKGROUND The selection of appropriate antibiotics to treat Gram-negative bacteraemia may be life-saving. Rapid methods of antimicrobial susceptibility testing have sought to guide early antibiotic selection and usage. We sought to evaluate whether a combination of chromogenic agar and six Etest gradient diffusion strips could be used to provide a clinically useful, direct rapid antimicrobial susceptibility test result following 4 hours of incubation.