"Antibiotic hardstop" on electronic prescribing: impact on antimicrobial stewardship initiatives in patients with community acquired pneumonia (CAP) and infective exacerbations of chronic obstructive pulmonary disease (IECOPD).

BACKGROUND: Antimicrobial resistance (AMR) remains a major public health threat and the exploration of interventions which may reduce inappropriate antimicrobial use are of particular interest. An Antibiotic Hardstop (AH) was included within the eMeds system introduced to the Central Coast Local Health District (CCLHD) in 2018. The function allows prescribers to set a predetermined time at which antibiotic orders would cease. By default, the function set prescribed length to 5 days with a view to encourage prescribers to review existing antimicrobial orders and reduce inappropriate use. METHODS: Records of adult inpatients prescribed broad spectrum antimicrobials with a registered indication of community acquired pneumonia (CAP) or an infective exacerbation of chronic obstructive pulmonary disease (IECOPD) between the 1st of March 2017 and 31st May 2017 for the pre eMeds cohort and 1st March 2019 and 31st May 2019 for the post eMeds cohort were randomly selected from our local health network's Guidance MS® system. Baseline demographics, antimicrobial prescribing records and documented adverse events related to the AH function were collated/analysed. The days of therapy (DOT) and length of therapy (LOT) for each encounter were calculated manually and results analysed using a two-tailed t-test or Mann-Whitney U test. RESULTS: Of patients eligible to have the AH function activated during their admission, 34% (n = 34) had the function deployed at least once. Following the introduction of eMeds mean DOT for the pooled indications cohort was reduced by 3.02 days (CI 95% 0.41-5.63, p < 0.05) and mean LOT by 1.97 days (CI 95% 0.39-3.55, p < 0.05). The hardstop function resulted in 2 cases of delayed or unintentionally ceased therapies. CONCLUSIONS: Following the introduction of electronic prescribing and AH, a significant reduction was observed in the DOT and LOT for antimicrobial use for inpatients with CAP and IECOPD without a significant increase in adverse events. Further research is required to determine the extent to which the AH functionality directly contributed to this effect and if the effect is present across a broader range of indications.

Comparison of different sepsis scoring systems and pathways: qSOFA, SIRS, Shapiro criteria and CEC SEPSIS KILLS pathway in bacteraemic and non-bacteraemic patients presenting to the emergency department.

BACKGROUND: Bacteraemia is associated with high morbidity and mortality, with delayed antibiotic treatment associated with poorer outcomes. Early identification is challenging, but clinically important. Multiple scoring systems have been developed to identify individuals in the broader categories of sepsis. We designed this study to assess the performance of existing scoring systems and pathways-CEC SEPSIS KILLS pathway (an Australian sepsis care package), quick sequential organ failure score (qSOFA), systemic inflammatory response syndrome (SIRS) and the Shapiro criteria. METHODS: This was a retrospective cohort study performed in two metropolitan hospitals in NSW, consisting of adult patients (> 18 years) with positive blood cultures containing a true pathogen and patients matched by age without positive blood cultures. Performance (sensitivity, specificity, and mortality prediction) of recognised sepsis and bacteraemia criteria and pathways-qSOFA, SIRS, Shapiro criteria and CEC SEPSIS KILLS pathway in the first 4 h following ED triage was assessed. RESULTS: There were 251 patients in each cohort. Sepsis-related mortality was higher in the bacteraemic group (OR 0.4, p = 0.03). Of the criteria studied, the modified Shapiro criteria had the highest sensitivity (88%) with modest specificity (37.85%), and qSOFA had the highest specificity (83.67%) with poor sensitivity (19.82%). SIRS had reasonable sensitivity (82.07%), with poor sensitivity (20.72%). The CEC SEPSIS pathway sensitivity of 70.1% and specificity of 71.1%. The SEPSIS KILLS was activated on only 14% of bacteraemic patients. CONCLUSION: The performance of all scoring systems and pathways was suboptimal in the identification of patients at risk of bacteraemia presenting to the emergency department.

Factors affecting the discharge of patients from hospital with seasonal influenza-the role of the Rapid Influenza testing in hospital discharges.

Influenza is a major cause of presentations to the emergency departments. Introduction of the Rapid Influenza tests has assisted with diagnosis and facilitated patient discharges. We designed this study to identify factors affecting hospital discharge and to understand the role of Rapid Influenza testing. A retrospective observational study of patients was done during influenza season in 2017. Clinical data was obtained from electronic medical records. Rapid Influenza testing was performed using Xpert Flu/RSV (Cepheid, USA). Univariate and multivariate analysis was done using SPSS Version 26 (IBM, NY). A total of 665 patients presented with laboratory-confirmed influenza. Patients discharged from the hospital were younger (median age 62 vs 68, p = 0.031). Patients with immunosuppression, chronic obstructive pulmonary disease (COPD) and pneumonia were more likely to be admitted to hospital. Rapid testing done with a turnaround (TAT) of 2 h (27.8% vs 17.8%, p = 0.002) and with a TAT of 6 h (55% vs 46.3%, p = 0.026) of the patient presentation was associated with a higher rate of hospital discharge. Median TAT of the RIT was 6 h (IQR 1-40 h). On multivariable analysis, RIT TAT of ≤ 2 h (OR 1.62, p = 0.013) was associated with higher likelihood of patients being discharged, whereas immunosuppressed patients (OR 2.25, p = 0.011), COPD (OR 2.42, p = 0.001) and pneumonia on presentation (OR 8.10, p < 0.001) were more likely to get admitted. Patients with COPD, pneumonia on presentation and those with immunosuppression are more likely to be admitted. Rapid Influenza tests can facilitate the discharge of patients from hospital.

Clinical impact of rapid diagnostics using Xpert Flu/RSV™ PCR on antimicrobial stewardship initiatives during influenza season.

BACKGROUND: Despite the availability of several rapid Influenza tests (RIT), the literature on its impact on antimicrobial stewardship programs (AMS) is minimal. Studies utilising rapid point of care tests (POCT) have shown benefit in terms of shortening antimicrobial therapy and prescriptions of antivirals. We designed this study to assess whether RIT had an impact on antibiotic cessation. METHODS: Xpert Flu/RSV (Cepheid, CA) was performed on all patients who presented with influenza-like illness (ILI) in 2017. Clinical data was collected from electronic medical records (eMR). Patients with RSV were not included. Turnaround time (TAT) for the test was time from specimen collection until when the result was either notified or appeared on eMR. Standard univariate analysis and multivariable regression analysis (MVRA) were done. RESULTS: A total of 665 patients tested positive-Influenza A (63%) and B (37%). After positive results, antimicrobials were ceased in 34% (226/665) or not given in 10% (71/665) cases. Median TAT was 7 h, with 50% of tests completed in less than 6 h 56% (368/665) of patients had their antibiotics continued. On MVRA, results of RIT within 6-12 h resulted in most antibiotic cessation (73%, OR 1.55, p = 0.01). It was found that antibiotics are continued in immunosuppressed patients (OR 2.88, p < 0.01), patients with pneumonia (OR 18.8, p < 0.01) and with underlying COPD (OR 2.43, p = 0.03). CONCLUSION: Influenza patients are more likely to have their antibiotics continued with underlying COPD, pneumonia, or immunosuppression. Results of RIT within 6-12 h can help clinicians in deciding on cessation of antibiotics in patients.

In-Hospital Surgery as a Risk Factor for Onset of AmpC-Producing Escherichia coli Blood Stream Infections.

There has been a progressive rise in the incidence of blood stream infections (BSI) caused by multidrug-resistant Gram-negative organisms (MDR GN), which cause increased morbidity and mortality. For this reason, recent studies have focused on risk factors of acquisition of carbapenemase-producing Enterobacteriaceae and extended-spectrum beta-lactamase producers. However, there is limited data on risk factors for BSI caused by AmpC-producing Enterobacteriaceae (AmpC EC), especially in low prevalence settings such as Australia. This study was performed to identify risk factors for acquisition of AmpC E. coli, using a retrospective matched case control design over a 3-year period. Patients with BSI caused by AmpC E. coli were matched with controls (third generation cephalosporin susceptible E. coli) by age and site of infection (n = 21). There was no significant difference in age, sex, clinical outcome, time to onset of BSI, recent antibiotic use (last 3 months), comorbidities (type 2 diabetes mellitus, renal failure) intensive care unit admission, underlying hematological condition, immunosuppressant use, APACHE II score, or any recent urological procedures (within last 3 months) between the two groups. On univariate analysis, the AmpC E. coli group were more likely to have had a surgical procedure in hospital and lived in a residential aged care facility. On multivariate logistic regression analysis, a recent surgical procedure was associated with the onset of AmpC E. coli BSI (Odd's Ratio (OR) 4.78, p = 0.034). We concluded that in a relatively low prevalence setting such as Australia, AmpC E. coli BSI is potentially associated with surgery performed in hospital due to previous antibiotic exposure and longer hospitalization.

Changes in antimicrobial prescribing behavior after the introduction of the antimicrobial stewardship program: A pre- and post-intervention survey.

The introduction of an antimicrobial stewardship (AMS) program is associated with a change in antimicrobial prescribing behavior. A proposed mechanism for this change is by impacting the prescribing etiquette described in qualitative studies. This study sought to detect a change in prescribing attitudes 12 months after the introduction of AMS and gauge utility of various AMS interventions. Surveys were distributed to doctors in two regional Australian hospitals on a convenience basis 6 months before, and 12 months after, the introduction of AMS. Agreement with 20 statements describing attitudes (cultural, behavioral and knowledge) towards antimicrobial prescribing was assessed on a 4-point Likert scale. Mean response scores were compared using the Wilcoxon Rank sum test. 155 responses were collected before the introduction of AMS, and 144 afterwards. After the introduction of AMS, an increase was observed in knowledge about available resources such as electronic decision support systems (EDSS) and therapeutic guidelines, with raised awareness about the support available through AMS rounds and the process to be followed when prescribing restricted antimicrobials. Additionally, doctors were less likely to rely on pharmacy to ascertain when an antimicrobial was restricted, depend on infectious diseases consultant advice and use past experience to guide antimicrobial prescribing. Responses to this survey indicate that positive changes to the antimicrobial prescribing etiquette may be achieved with the introduction of an AMS program. Use of EDSS and other resources such as evidence-based guidelines are perceived to be important to drive rational antimicrobial prescribing within AMS programs.

Evaluation of a Commercial Multiplex PCR for Rapid Detection of Multi Drug Resistant Gram Negative Infections.

INTRODUCTION: Community and healthcare associated infections caused by multi-drug resistant gram negative organisms (MDR GN) represent a worldwide threat. Nucleic Acid Detection tests are becoming more common for their detection; however they can be expensive requiring specialised equipment and local expertise. This study was done to evaluate the utility of a commercial multiplex tandem (MT) PCR for detection of MDR GN. METHODS: The study was done on stored laboratory MDR GN isolates from sterile and non-sterile specimens (n=126, out of stored 567 organisms). Laboratory validation of the MT PCR was done to evaluate sensitivity, specificity and agreement with the current phenotypic methods used in the laboratory. Amplicon sequencing was also done on selected isolates for assessing performance characteristics. Workflow and cost implications of the MT PCR were evaluated. RESULTS: The sensitivity and specificity of the MT PCR were calculated to be 95% and 96.7% respectively. Agreement with the phenotypic methods was 80%. Major lack of agreement was seen in detection of AmpC beta lactamase in enterobacteriaceae and carbapenemase in non-fermenters. Agreement of the MT PCR with another multiplex PCR was found to be 87%. Amplicon sequencing confirmed the genotype detected by MT PCR in 94.2 % of cases tested. Time to result was faster for the MT PCR but cost per test was higher. CONCLUSION: This study shows that with carefully chosen targets for detection of resistance genes in MDR GN, rapid and efficient identification is possible. MT PCR was sensitive and specific and likely more accurate than phenotypic methods.

Investigating an outbreak of staphylococcal food poisoning among travellers across two Australian states.

INTRODUCTION: Staphylococcus aureus is a common cause of staphylococcal food poisoning in Australia with several outbreaks associated with foods prepared by commercial caterers. Laboratory testing on cases of gastrointestinal illness caused by enterotoxin-producing S. aureus is not routinely done as this condition is self-limiting. Hence outbreaks of such illness may go undetected. METHODS: A retrospective cohort study was conducted among a group of tourists who were hospitalized in Sydney shortly after flying from Queensland. The group had consumed food prepared by a restaurant on the Gold Coast before transit. Laboratory analyses on stool specimens were conducted in Sydney. An environmental assessment of the restaurant in the Gold Coast was conducted, and environmental specimens were assessed for contamination. RESULTS: Epidemiological investigations linked the outbreak to a restaurant in the Gold Coast where the suspected food was produced. Stool samples from two of the hospitalized cases were confirmed to have enterotoxin-producing S. aureus, and several environmental samples were found to be contaminated with S. aureus as well. Investigations suggested that absence of hand washing and other unhygienic food handling at the implicated restaurant was the likely cause of this outbreak. CONCLUSION: Food poisoning due to toxin-mediated S. aureus is frequently undetected and underreported. Public health units should consider toxin-producing pathogens such as S. aureus when investigating outbreaks where vomiting is the predominant symptom and occurs rapidly after consuming food.

Cefepime induced acute interstitial nephritis--a case report.

BACKGROUND: Nephrotoxicity due to drugs especially beta lactams and cephalosporins has been well recognised. Cefepime is a fourth-generation cephalosporin that is widely prescribed with few severe adverse reactions reported. Although cefepime induced neurotoxicity has frequently been reported, there is yet no reported case of acute interstitial nephritis caused by this drug. We report a biopsy proven case of acute kidney injury due to acute interstitial nephritis associated with use of cefepime for treatment of mastoiditis and temporal bone osteomyelitis. CASE PRESENTATION: A 62-year-old Caucasian female presented with symptoms of right sided mastoiditis. A brain Magnetic Resonance Imaging scan revealed presence of right sided mastoiditis with concurrent temporal bone osteomyelitis. Microbiological specimen isolated an Escherichia coli. Therapy was commenced with intravenous cefepime. After 4 weeks of therapy with intravenous cefepime she developed acute kidney injury. No other medications were taken by the patient. Urine analysis revealed non-nephrotic range proteinuria. There was no red cell casts or white cell casts. Renal biopsy confirmed acute interstitial nephritis as cause of acute kidney injury. Cefepime therapy was ceased and treatment with ciprofloxacin was given to complete the treatment course. Renal function improved only partially with conservative management without any corticosteroid use. To our knowledge this is the first report of cefepime induced interstitial nephritis. CONCLUSIONS: Although cefepime has been considered to be a safe antibiotic from nephrotoxicity point, like other cephalosporins this adverse effect can occur rarely. Physicians need to be mindful of nephrotoxicity associated with its use and careful monitoring of renal parameters should be performed in patients on prolonged therapy with cefepime.

Post Liposuction Mycobacterium Abscessus Surgical Site Infection in a Returned Medical tourist Complicated by a Paradoxical Reaction During Treatment.

Rapidly growing mycobacterial skin and soft tissue infections are known to complicate cosmetic surgical procedures. Treatment consists of more surgery and prolonged antibiotic therapy guided by drug susceptibility testing. Paradoxical reactions occurring during antibiotic therapy can further complicate treatment of non-tuberculous mycobacterial infections. We report a case of post liposuction Mycobacterium abscessus surgical site infection in a returned medical tourist and occurrence of paradox during treatment.

Investigating an outbreak of staphylococcal food poisoning among travellers across two Australian states

Introduction：Staphylococcus aureus is a common cause of staphylococcal food poisoning in Australia with several outbreaks associated with foods prepared by commercial caterers. Laboratory testing on cases of gastrointestinal illness caused by enterotoxin-producing S. aureus is not routinely done as this condition is self-limiting. Hence outbreaks of such illness may go undetected.Methods：A retrospective cohort study was conducted among a group of tourists who were hospitalized in Sydney shortly after flying from Queensland. The group had consumed food prepared by a restaurant on the Gold Coast before transit. Laboratory analyses on stool specimens were conducted in Sydney. An environmental assessment of the restaurant in the Gold Coast was conducted, and environmental specimens were assessed for contamination.Results：Epidemiological investigations linked the outbreak to a restaurant in the Gold Coast where the suspected food was produced. Stool samples from two of the hospitalized cases were confirmed to have enterotoxin-producing S. aureus, and several environmental samples were found to be contaminated with S. aureus as well. Investigations suggested that absence of hand washing and other unhygienic food handling at the implicated restaurant was the likely cause of this outbreak.Conclusion：Food poisoning due to toxin-mediated S. aureus is frequently undetected and underreported. Public health units should consider toxin-producing pathogens such as S. aureus when investigating outbreaks where vomiting is the predominant symptom and occurs rapidly after consuming food.

Uncommon manifestations of Listeria monocytogenes infection.

BACKGROUND: Listeria monocytogenes causes gastroenteritis, meningitis and bacteraemia in immunocompromised, pregnant patients, the elderly as well in immunocompetent patients. Focal infections with this organism are uncommon, especially in sporadic (non-outbreak) setting, require high index of suspicion and are challenging to diagnose. We present 3 cases of Listeria monocytogenes presenting as focal infections to our hospitals, all of which are the first reported cases from Australia. CASE PRESENTATION: Three unrelated cases of unique focal infections caused by Listeria monocytogenes are presented. 1) A 73 year old Caucasian lady on immunosuppression for colorectal cancer presented with prosthetic knee joint septic arthritis, 2) An 83 year old Caucasian man presented with prosthetic vascular graft infection and 3) A 60 year old Asian man with perianal abscess. Except for case 1, the other cases had a prolonged duration of symptoms on presentation. Listeria was not thought to be causative organism in any of these cases until microbiological specimens isolated the organism. Matrix Associated Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) assisted in making an earlier diagnosis of the infection in all three cases. All of these patients had Listeria monocytogenes isolated from clinical specimens. They were managed with antibiotics and surgery with favourable outcomes. Public health investigations to determine any dietary association were done, however no intervention was thought to be necessary in any of the cases except provide dietary advice. The first two cases highlight the importance of microbiological sampling in serious infections for definitive antibiotic therapy to be administered. CONCLUSION: Sporadic focal infections with Listeria occur infrequently and are often not diagnosed till culture results from microbiological specimens become available. Dietary history should be an important aspect of thorough clinical history and food consumption advice is crucial in immunocompromised patients on similar lines as given to pregnant women about listeriosis.

Seeking clarity within cloudy effluents: differentiating fungal from bacterial peritonitis in peritoneal dialysis patients.

BACKGROUND: Fungal peritonitis is a serious complication of peritoneal dialysis (PD) therapy with the majority of patients ceasing PD permanently. The aims of this study were to identify risk factors and clinical associations that may discriminate between fungal from bacterial peritonitis. METHODS: We retrospectively identified episodes of fungal peritonitis from 2001-2010 in PD patients at Liverpool and Westmead Hospitals (Australia). Fungal peritonitis cases were matched in a 1:2 ratio with patients with bacterial peritonitis from each institution's dialysis registry, occurring closest in time to the fungal episode. Patient demographic, clinical and outcome data were obtained from the medical records. RESULTS: Thirty-nine episodes of fungal peritonitis (rate of 0.02 episodes per patient-year of dialysis) were matched with 78 episodes of bacterial peritonitis. Candida species were the commonest pathogens (35/39; 90% episodes) with Candida albicans (37%), Candida parapsilosis (32%) and Candida glabrata (13%) the most frequently isolated species. Compared to bacterial peritonitis, fungal peritonitis patients had received PD for significantly longer (1133 vs. 775 catheter-days; p = 0.016), were more likely to have had previous episodes of bacterial peritonitis (51% vs. 10%; p = 0.01), and to have received prior antibacterial therapy (51% vs. 10%; p = 0.01). Patients with fungal peritonitis were less likely to have fever and abdominal pain on presentation, but had higher rates of PD catheter removal (79% vs. 22%; p<0.005), and permanent transfer to haemodialysis (87% vs. 24%; p<0.005). Hospital length of stay was significantly longer in patients with fungal peritonitis (26.1 days vs. 12.6 days; p = 0.017), but the all-cause 30-day mortality rate was similar in both groups. Fluconazole was a suitable empiric antifungal agent; with no Candida resistance detected. CONCLUSION: Prompt recognition of clinical risk factors, initiation of antifungal therapy and removal of PD catheters are key considerations in optimising outcomes.