Epidemiology and impact of methicillin-sensitive Staphylococcus aureus with ß-lactam antibiotic inoculum effects in adults with cystic fibrosis.

Staphylococcus aureus is the most prevalent cystic fibrosis (CF) pathogen. Several phenotypes are associated with worsened CF clinical outcomes including methicillin-resistance and small-colony-variants. The inoculum effect (IE) is characterized by reduced ß-lactam susceptibility when assessed at high inoculum. The IE associates with worse outcomes in bacteremia and other high-density infections, and may therefore be relevant to CF. The prevalence of IE amongst a CF cohort (age ≥18 years), followed from 2013 to 2016, was investigated. Yearly methicillin-sensitive S. aureus (MSSA) isolates were screened at standard (5 × 105 CFU/mL) and high (5 × 107 CFU/mL) inoculum against narrow-spectrum anti-Staphylococcal ß-lactams and those with anti-pseudomonal activity common to CF. A ≥ 4-fold increase in minimum inhibitory concentration between standard and high inoculum defined IE. Isolates underwent blaZ sequencing and genotyping and were compared against published genomes. Fifty-six percent (99/177) of individuals had MSSA infection. MSSA was observed at ≥105 CFU/mL in 44.8% of entry sputum samples. The prevalence of the IE was 25.0%-cefazolin; 13.5%-cloxacillin; 0%-meropenem; 1.0%-cefepime; 5.2%-ceftazidime; and 34.4%-piperacillin-tazobactam amongst baseline MSSA isolates assessed. blaZ A associated with cefazolin IE (P = 0.0011), whereas blaZ C associated with piperacillin-tazobactam IE (P < 0.0001). Baseline demographics did not reveal specific risk factors for IE-associated infections, nor were long-term outcomes different. Herein, we observed the IE in CF-derived MSSA disproportionally for cefazolin and piperacillin-tazobactam and this phenotype strongly associated with underlying blaZ genotype. The confirmation of CF being a high density infection, and the identification of high prevalence of MSSA with IE in CF supports the need for prospective pulmonary exacerbation treatment studies to understand the impact of this phenotype.

The development and application of a molecular community profiling strategy to identify polymicrobial bacterial DNA in the whole blood of septic patients.

BACKGROUND: The application of molecular based diagnostics in sepsis has had limited success to date. Molecular community profiling methods have indicated that polymicrobial infections are more common than suggested by standard clinical culture. A molecular profiling approach was developed to investigate the propensity for polymicrobial infections in patients predicted to have bacterial sepsis. RESULTS: Disruption of blood cells with saponin and hypotonic shock enabled the recovery of microbial cells with no significant changes in microbial growth when compared to CFU/ml values immediately prior to the addition of saponin. DNA extraction included a cell-wall digestion step with both lysozyme and mutanolysin, which increased the recovery of terminal restriction fragments by 2.4 fold from diverse organisms. Efficiencies of recovery and limits of detection using Illumina sequencing of the 16S rRNA V3 region were determined for both viable cells and DNA using mock bacterial communities inoculated into whole blood. Bacteria from pre-defined communities could be recovered following lysis and removal of host cells with >97% recovery of total DNA present. Applying the molecular profiling methodology to three septic patients in the intensive care unit revealed microbial DNA from blood had consistent alignment with cultured organisms from the primary infection site providing evidence for a bloodstream infection in the absence of a clinical lab positive blood culture result in two of the three cases. In addition, the molecular profiling indicated greater diversity was present in the primary infection sample when compared to clinical diagnostic culture. CONCLUSIONS: A method for analyzing bacterial DNA from whole blood was developed in order to characterize the bacterial DNA profile of sepsis infections. Preliminary results indicated that sepsis infections were polymicrobial in nature with the bacterial DNA recovered suggesting a more complex etiology when compared to blood culture data.

Infection prevention and control measures for acute respiratory infections in healthcare settings: an update.

Viruses account for the majority of the acute respiratory tract infections (ARIs) globally with a mortality exceeding 4 million deaths per year. The most commonly encountered viruses, in order of frequency, include influenza, respiratory syncytial virus, parainfluenza and adenovirus. Current evidence suggests that the major mode of transmission of ARls is through large droplets, but transmission through contact (including hand contamination with subsequent self-inoculation) and infectious respiratory aerosols of various sizes and at short range (coined as "opportunistic" airborne transmission) may also occur for some pathogens. Opportunistic airborne transmission may occur when conducting highrisk aerosol generating procedures and airborne precautions will be required in this setting. General infection control measures effective for all respiratory viral infections are reviewed and followed by discussion on some of the common viruses, including severe acute respiratory syndrome (SARS) coronavirus and the recently discovered novel coronavirus.

Viral cultures, cycle threshold values and viral load estimation for assessing SARS-CoV-2 infectiousness in haematopoietic stem cell and solid organ transplant patients: a systematic review.

BACKGROUND: Solid organ and haematopoietic stem cell transplant recipients are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) than non-transplant recipients due to immunosuppression, and may pose a continued transmission risk, especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation. OBJECTIVES: To investigate the relationship between serial SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) value or cycle of quantification value, or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture, including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship, in transplant recipients. METHODS: LitCovid, medRxiv, Google Scholar and the World Health Organization COVID-19 database were searched from 1st November 2019 to 26th October 2022. Studies reporting relevant data (results from serial RT-PCR testing and viral culture data from the same respiratory samples) for transplant recipients with SARS-CoV-2 infection were included in this systematic review: Methodological quality was assessed using five criteria, and the data were synthesized narratively and graphically. RESULTS: Thirteen case reports and case series reporting on 41 transplant recipients (22 renal, five cardiac, one bone marrow, two liver, one bilateral lung and 10 blood stem cell) were included in this review. A relationship was observed between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Three individuals shed replication-competent viruses for >100 days after symptom onset. Lack of standardization of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, the majority of transplant recipients stopped shedding replication-competent viruses when the Ct value was >30 despite differences across platforms. CONCLUSIONS: Viral burden is a reasonable proxy for infectivity when considered within the context of the clinical status of each patient. Standardized study design and reporting are essential to standardize guidance based on an increasing evidence base.

A two-ward acute care hospital outbreak of SARS-CoV-2 delta variant including a point-source outbreak associated with the use of a mobile vital signs cart and sub-optimal doffing of personal protective equipment.

BACKGROUND: The arrival of the Delta variant of SARS-CoV-2 was associated with increased transmissibility and illness of greater severity. Reports of nosocomial outbreaks of Delta variant COVID-19 in acute care hospitals have been described but control measures varied widely. AIM: Epidemiological investigation of a linked two-ward COVID-19 Delta variant outbreak was conducted to elucidate its source, risk factors, and control measures. METHODS: Investigations included epidemiologic analysis, detailed case review serial SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing of patients and healthcare workers (HCWs), viral culture, environmental swabbing, HCW-unaware personal protective equipment (PPE) audits, ventilation assessments, and the use of whole genome sequencing (WGS). FINDINGS: This linked two-ward outbreak resulted in 17 patient and 12 HCW cases, despite an 83% vaccination rate. In this setting, suboptimal adherence and compliance to PPE protocols, suboptimal hand hygiene, multi-bedded rooms, and a contaminated vital signs cart with potential fomite or spread via the hands of HCWs were identified as significant risk factors for nosocomial COVID-19 infection. Sudden onset of symptoms, within 72 h, was observed in 79% of all Ward 2 patients, and 93% of all cases (patients and HCWs) on Ward 2 occurred within one incubation period, consistent with a point-source outbreak. RT-PCR assays showed low cycle threshold (CT) values, indicating high viral load from environmental swabs including the vital signs cart. WGS results with ≤3 SNP differences between specimens were observed. CONCLUSION: Outbreaks on both wards settled rapidly, within 3 weeks, using a `back-to-basics' approach without extraordinary measures or changes to standard PPE requirements. Strict adherence to recommended PPE, hand hygiene, education, co-operation from HCWs, including testing and interviews, and additional measures such as limiting movement of patients and staff temporarily were all deemed to have contributed to prompt resolution of the outbreak.

Viral cultures for assessing fomite transmission of SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: The role of fomites in the transmission of SARS-CoV-2 is unclear. AIM: To assess whether SARS-CoV-2 can be transmitted through fomites, using evidence from viral culture studies. METHODS: Searches were conducted in the World Health Organization COVID-19 Database, PubMed, LitCovid, medRxiv, and Google Scholar to December 31st, 2021. Studies that investigated fomite transmission and performed viral culture to assess the cytopathic effect (CPE) of positive fomite samples and confirmation of SARS-CoV-2 as the cause of the CPE were included. The risk of bias using a checklist modified from the modified Quality Assessment of Diagnostic Accuracy Studies - 2 (QUADAS-2) criteria was assessed. FINDINGS: Twenty-three studies were included. The overall risk of bias was moderate. Five studies demonstrated replication-competent virus from fomite cultures and three used genome sequencing to match fomite samples with human clinical specimens. The mean cycle threshold (CT) of samples with positive viral culture was significantly lower compared with cultured samples that returned negative results (standardized mean difference: -1.45; 95% confidence interval (CI): -2.00 to -0.90; I2 = 0%; P < 0.00001). The likelihood of isolating replication-competent virus was significantly greater when CT was <30 (relative risk: 3.10; 95% CI: 1.32 to 7.31; I2 = 71%; P = 0.01). Infectious specimens were mostly detected within seven days of symptom onset. One study showed possible transmission of SARS-CoV-2 from fomites to humans. CONCLUSION: The evidence from published studies suggests that replication-competent SARS-CoV-2 is present on fomites. Replication-competent SARS-CoV-2 is significantly more likely when the PCR CT for clinical specimens and fomite samples is <30. Further studies should investigate the duration of infectiousness of SARS-CoV-2 and the frequency of transmission from fomites.

Rationale and development of a business case for antimicrobial stewardship programs in acute care hospital settings.

Background: Antimicrobial stewardship programs (ASPs) have been shown to reduce inappropriate antimicrobial use and its consequences. However, these programs lack legislative requirements in many places and it can be difficult to determine what human resources are required for these programs and how to create a business case to present to hospital administrators for program funding. The objectives of the current paper were to review legislative requirements and outline human resource requirements for ASPs, and to create a base business case for ASPs. Methods: A working group of antimicrobial stewardship experts from across Canada met to discuss the necessary components for creation of a business case for antimicrobial stewardship. A narrative review of the literature of the regulatory requirements and human resource recommendations for ASPs was conducted. Informed by the review and using a consensus decision-making process, the expert working group developed human resource recommendations based on a 1000 bed acute care health care facility in Canada. A spreadsheet based business case model for ASPs was also created. Results: Legislative and /or regulatory requirements for ASPs were found in 2 countries and one state jurisdiction. The literature review and consensus development process recommended the following minimum human resources complement: 1 physician, 3 pharmacists, 0.5 program administrative and coordination support, and 0.4 data analyst support as full time equivalents (FTEs) per 1000 acute care beds. Necessary components for the business case model, including the human resource requirements, were determined to create a spreadsheet based model. Conclusions: There is evidence to support the negative outcomes of inappropriate antimicrobial use as well as the benefits of ASPs. Legislative and /or regulatory requirements for ASPs are not common. The available evidence for human resource recommendations for ASPs using a narrative review process was examined and a base business case modelling scenario was created. As regulatory requirements for ASPs increase, it will be necessary to create accurate business cases for ASPs in order to obtain the necessary funding to render these programs successful.

Treatment of infections caused by metallo-beta-lactamase-producing Pseudomonas aeruginosa in the Calgary Health Region.

This study reviewed 56 patients with significant metallo-beta-lactamase (MBL)-producing Pseudomonas aeruginosa infections between May 2002 and March 2004 to identify features associated with mortality. Immunosuppression (p 0.002), bacteraemia (p 0.08) and inadequate antimicrobial therapy (p <0.001) were associated with death. Among those patients treated with adequate therapy, the use of multiple drug treatment regimens (two or three active agents) was associated with a non-significant two-fold increase in survival (p 0.45). Further prospective studies are warranted to determine the optimal treatment of MBL-producing P. aeruginosa infections.

Cerebrospinal fluid as a diagnostic body fluid.

The cerebrospinal fluid is a dynamic, metabolically active substance that has many important functions. It is invaluable as a diagnostic aid in the evaluation of inflammatory conditions, infectious or noninfectious, involving the brain, spinal cord, and meninges. The cerebrospinal fluid may be obtained with relative ease with the use of lumbar puncture, but failing this, alternative techniques are available. With the judicious use of the computerized axial tomographic scan, the removal of cerebrospinal fluid has little attendant risk. Age-related and compartmental variations in chemical and cellular composition are important considerations in the interpretation of results. Alterations in cerebrospinal fluid constituents from different pathologic processes may be similar in certain circumstances and cause interpretation difficulties.

A comparison of multifaceted versus Clostridium difficile-focused VRE surveillance strategies in a low-prevalence setting.

We compared our current screening strategy for vancomycin-resistant Enterococcus (VRE) with a focused strategy that screens all stool samples sent for Clostridium difficile toxin assay but limits rectal swab screening to wards with new VRE cases detected via C. difficile samples. The proposed strategy detects 72.7% of new VRE cases, with substantial cost savings.

Handwashing practices in an intensive care unit: the effects of an educational program and its relationship to infection rates.

Handwashing is the single most important procedure in the prevention of nosocomial infections and yet it remains the most violated of all infection control procedures. With a sequential intervention study in an intensive care unit we have demonstrated that poor handwashing practices are associated with a high nosocomial infection rate, whereas good handwashing practices are associated with a low nosocomial infection rate. An educational and enforcement program designed to improve handwashing procedures can significantly reduce endemic nosocomial infection rates.

Retrospective analysis of the clinical and economic outcomes of twice-daily dosing of cefotaxime in a Canadian tertiary care institution.

A retrospective analysis of the clinical and economic outcome of a regimen of cefotaxime 1 g given every 12 h was conducted following the introduction of an institutional policy recommending this new dosing strategy. Patients were identified from a log order entry in the pharmacy, and the medical records were reviewed using a standardized data collection form. Explicit criteria were applied for the indications for antimicrobial therapy, presence of infection, and outcome parameters. A total of 60 patients with a mean (+/- SD) age of 56.2 (+/- 17.8) years and a mean (+/- SD) length of stay of 20.75 (+/- 18.1) days were identified. Of these, 48 (80%) were found to have a clinically or microbiologically documented infection, and of the 42 patients who could be assessed accordingly to the criteria chosen, 37 (88%) had a favorable clinical response; 21 patients (35%) received cefotaxime alone. The costs for administration of cefotaxime have decreased by approximately 30% since the introduction of this new dosing regimen.

A multicenter, open comparative study of parenteral cefotaxime and ceftriaxone in the treatment of nosocomial lower respiratory tract infections.

A multicenter Canadian study enrolled 74 persons to compare low-dose cefotaxime at 1 g every 8 hr to ceftriaxone 1 g every 12 hr in patients with nosocomial pneumonia. Of 57 evaluable patients (30 cefotaxime and 27 ceftriaxone) in this preliminary report, 93% responded to therapy in both groups. Ceftriaxone patients tended to have more side effects (14.2%). This study is continuing to accrue patients to achieve 100 evaluable patients. Interim data, however, support the continued use of low-dose cefotaxime as an appropriate alternative for clinically effective and cost-effective management of nosocomially acquired pneumonia.

Pneumonia with pleural effusion due to Legionella pneumophila serogroup Lansing 3.

We describe a case of pneumonia with pleural effusion due to Legionella pneumophila serogroup Lansing 3 in a human immunodeficiency virus-infected person. The 55-year-old man had been treated with immunosuppressive agents for hypersensitivity pneumonitis.

The cost of health care for AIDS patients in Saskatchewan.

The medical records of 19 patients with acquired immune deficiency syndrome (aids) were reviewed in an attempt to estimate their health care costs. The patients were all male, members of high risk groups and diagnosed between April 1985 and February 1988. Twelve of the patients died; they lived a mean of 240 days (range 0 to 580) after diagnosis, were admitted three times (range one to six) to hospital for 65 total days (range one to 148) for a cost per patient of $33,721 (range $2,768 to $64,981) for inpatient care. They made five (range zero to 25) office visits per patient costing $196 per patient (range $0 to $4,999) for outpatient care. The seven survivors (one was lost to follow-up) have lived 375 days (range 186 to 551) since diagnosis, have been admitted to hospital two times (range zero to seven) for 30 total days (range zero to 86) for a total cost per patient of $14,223 (range $0 to $39,410) for inpatient care. They have made 11 office/emergency room visits (range zero to 46) costing in total $4322 (range $0 to $13,605) for outpatient care. The total expenditure was $546,332 ($28,754 per patient), of which total fees to physicians were $37,210 (6.8%), and estimated costs of laboratory tests $117,917 (21.6%), drugs $36,930 (6.7%), and medical imaging $20,794 (3.8%). Patients now deceased cost $416,445 (mean $34,704 per patient), accounting for 76.2% of overall expenditures. The average medical/surgical and drug costs per patient day in hospital were greater for aids patients than for the average medical/surgical patient in the authors' institution.

Double-blind prospective randomized study comparing topical mupirocin and placebo for the prevention of infection associated with central venous catheters.

OBJECTIVE: To compare the incidence of exit site colonization, local catheter-related infection and catheter-related bacteremia in patients randomized to receive either topical 2% mupirocin or placebo at the catheter exit site. PATIENTS AND METHODS: Patients requiring central venous catheters for more than three days were randomized to receive in a double-blind fashion either topical mupirocin or an identical placebo at the exit site three times weekly at the time of dressing change. Insertion, site care and removal of catheters were standardized. Serial semiquantitataive cultures of the skin at the catheter insertion site were performed using a sterile 25 cm(2) template. The distal and proximal catheter segments were cultured using a standardized semiquantitative technique, and any suspect catheter-related bacteremia was investigated with two sets of peripheral blood cultures, a 10 mL sample of infusate and clinical assessment. Both univariate and multivariate analyses were conducted on individual risk factors to determine factors that might influence the outcomes of local or systemic catheter-related infection. RESULTS: Local catheter-related infection (defined as more than 15 colony forming units [cfu] on culture of the proximal or distal catheter segment) occurred in six of 57 (10.5%) in the mupirocin group versus 18 of 69 (26%) in the placebo group (P<0.05) for the distal catheter segments and in one of 40 (2.5%) versus 13 of 47 (27.6%) for the proximal segments in the mupirocin and placebo groups (P<0.006), respectively. Catheter-related bacteremia occurred in one of 57 (1.8%) of the mupirocin group but in five of 69 (7.2%) of the placebo group (P=0.15). Stepwise logistic regression revealed that cutaneous colonization at the insertion site of at least 10(3) cfu/mL/25 cm(2) (OR 2.6; CI 1.0 to 6.9) and the use of placebo (OR 3.3; CI 1.2 to 9.0) were significant factors predicting local catheter-related infection; whereas mupirocin was associated with reciprocal protective effect (OR 0.3; 95% CI 0.1 to 0.8). CONCLUSIONS: These findings suggest that patients receiving topical mupirocin at the exit site for long term central venous catheters have significantly less local catheter-related infection, and there is a trend towards less catheter-related bacteremia.

The emerging epidemiology of VRE in Canada: results of the CNISP Passive Reporting Network, 1994 to 1998.

OBJECTIVE: To provide a rapid and efficient means of collecting descriptive epidemiological data on occurrences of vancomycin-resistant enterococcus (VRE) in Canada. DESIGN AND METHODS: Passive reporting of data on individual or cluster occurrences of VRE using a one-page surveillance form. SETTING: The surveillance form was periodically distributed to all Canadian Hospital Epidemiology Committee members, Community and Hospital Infection Control Association members, L'Association des professionnels pour la prevention des infections members and provincial laboratories, representing 650 health care facilities across Canada. PATIENTS: Patients colonized or infected with VRE within Canadian health care facilities. RESULTS: Until the end of 1998, 263 reports of VRE were received from 113 health care facilities in 10 provinces, comprising a total of 1315 cases of VRE, with 1246 cases colonized (94.7%), 61 infected (4.6%)and eight of unknown status. (0.6%). VRE occurrences were reported in 56% of acute care teaching facilities and 38% of acute care community facilities. All facilities of more than 800 beds reported VRE occurences compared with only 10% of facilities with less than 200 beds (r2=0.86). Medical and surgical wards accounted for 51.4% of the reported VRE occurences. Sixty-five (24.7%) reports indicated an index case was from a foreign country, with 85.2% from the United States and 14.8% from other countries. Some type of screening was conducted in 50% of the sites. CONCLUSIONS: A VRE passive reporting network provided a rapid and efficient means of providing data on the evolving epidemiology of VRE in Canada.