Treatment for infections with carbapenem-resistant Enterobacteriaceae: what options do we still have?

The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is increasingly becoming a major challenge in clinical and public health settings. To date, the treatment for serious CRE infections remains difficult. The intelligent use of antimicrobials and effective infection control strategies is crucial to prevent further CRE spread. Early consultation with experts in the treatment of infections with multidrug-resistant organisms is valuable in patient management. This brief review will focus on the current, yet limited, treatment options for CRE infections.

Surgical Site Infection Prevention Using "Strike Teams": The Experience of an Academic Colorectal Surgical Department.

ABSTRACT: Surgical site infections (SSIs) are healthcare-acquired infections with substantial morbidity. Surgical site infection persist because of low adherence to prevention bundles comprising multiple infection control elements. We propose the "Strike Team" as an implementation strategy to improve adherence and reduce SSI in colorectal surgery. At an academic medical center, a multidisciplinary Strike Team met monthly to review colorectal SSI cases, audit and discuss barriers to adherence to SSI prevention bundle, and propose actionable feedback. The latter was shared with frontline clinicians by the Strike Team's surgical leaders in everyday practice. Colorectal SSI rates and bundle adherence data were disseminated quarterly via the hospital intranet and reviewed with surgeons at departmental meetings. Trends in adherence and SSI rates were analyzed by regression analysis using a time series model. While the Strike Team was active, adherence to antibiotic prophylaxis, maintenance of normoglycemia, and standardized intraoperative skin preparation significantly increased (p < .05). There was a trend toward statistically significant reduction in SSI (p = .07), although it was not maintained once the Strike Team activity was disrupted by the COVID-19 pandemic. Colorectal SSI prevention requires a resource-intensive, multidisciplinary approach with numerous strategies to improve adherence to infection control bundles, as illustrated by our SSI Strike Team experience.

A scoping review of bacterial resistance among inpatients amidst the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic disrupted antimicrobial stewardship and infection prevention operations worldwide, raising concerns for an acceleration of antimicrobial resistance (AMR). Therefore, we aimed to define the scope of peer reviewed research comparing AMR in inpatient bacterial clinical cultures before and after the start of the COVID-19 pandemic. METHODS: We conducted a scoping review and searched PubMed, Scopus, and Web of Science through 15 June 2023. Our inclusion criteria were: (1) English language, (2) primary evidence, (3) peer-reviewed, (4) clinical culture data from humans, (5) AMR data for at least one bacterial order/species, (6) inpatient setting, (7) use of statistical testing to evaluate AMR data before and during the COVID-19 pandemic. Reviewers extracted country, study design, type of analysis, study period, setting and population, number of positive cultures or isolates, culture type(s), method of AMR analysis, organisms, and AMR results. Study results were organised by organism and antibiotic class or resistance mechanism. AMR results are also summarised by individual study and across all studies. RESULTS: In total, 4805 articles were identified with 55 papers meeting inclusion criteria. Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus were the most commonly studied organisms. There were 464 bacterial AMR results across all studies with 82 (18%) increase, 71 (15%) decrease, and 311 (67%) no change results. CONCLUSIONS: The literature examining the impact of COVID-19 on AMR among inpatients is diverse with most results reflecting no change pre/post pandemic. Ongoing inquiry is needed into evolving patterns in AMR post COVID-19.

Understanding clinical implementation coordinators' experiences in deploying evidence-based interventions.

PURPOSE: The fluoroquinolone restriction for the prevention of Clostridioides difficile infection (FIRST) trial is a multisite clinical study in which sites carry out a preauthorization process via electronic health record-based best-practice alert (BPA) to optimize the use of fluoroquinolone antibiotics in acute care settings. Our research team worked closely with clinical implementation coordinators to facilitate the dissemination and implementation of this evidence-based intervention. Clinical implementation coordinators within the antibiotic stewardship team (AST) played a pivotal role in the implementation process; however, considerable research is needed to further understand their role. In this study, we aimed to (1) describe the roles and responsibilities of clinical implementation coordinators within ASTs and (2) identify facilitators and barriers coordinators experienced within the implementation process. METHODS: We conducted a directed content analysis of semistructured interviews, implementation diaries, and check-in meetings utilizing the conceptual framework of middle managers' roles in innovation implementation in healthcare from Urquhart et al. RESULTS: Clinical implementation coordinators performed a variety of roles vital to the implementation's success, including gathering and compiling information for BPA design, preparing staff, organizing meetings, connecting relevant stakeholders, evaluating clinical efficacy, and participating in the innovation as clinicians. Coordinators identified organizational staffing models and COVID-19 interruptions as the main barriers. Facilitators included AST empowerment, positive relationships with staff and oversight/governance committees, and using diverse implementation strategies. CONCLUSION: When implementing healthcare innovations, clinical implementation coordinators facilitated the implementation process through their roles and responsibilities and acted as strategic partners in improving the adoption and sustainability of a fluoroquinolone preauthorization protocol.

A severe acute respiratory coronavirus virus 2 (SARS-CoV-2) nosocomial cluster with inter-facility spread: Lessons learned.

BACKGROUND: Despite infection control guidance, sporadic nosocomial coronavirus disease 2019 (COVID-19) outbreaks occur. We describe a complex severe acute respiratory coronavirus virus 2 (SARS-CoV-2) cluster with interfacility spread during the SARS-CoV-2 δ (delta) pandemic surge in the Midwest. SETTING: This study was conducted in (1) a hematology-oncology ward in a regional academic medical center and (2) a geographically distant acute rehabilitation hospital. METHODS: We conducted contact tracing for each COVID-19 case to identify healthcare exposures within 14 days prior to diagnosis. Liberal testing was performed for asymptomatic carriage for patients and staff. Whole-genome sequencing was conducted for all available clinical isolates from patients and healthcare workers (HCWs) to identify transmission clusters. RESULTS: In the immunosuppressed ward, 19 cases (4 patients, 15 HCWs) shared a genetically related SARS-CoV-2 isolate. Of these 4 patients, 3 died in the hospital or within 1 week of discharge. The suspected index case was a patient with new dyspnea, diagnosed during preprocedure screening. In the rehabilitation hospital, 20 cases (5 patients and 15 HCWs) positive for COVID-19, of whom 2 patients and 3 HCWs had an isolate genetically related to the above cluster. The suspected index case was a patient from the immune suppressed ward whose positive status was not detected at admission to the rehabilitation facility. Our response to this cluster included the following interventions in both settings: restricting visitors, restricting learners, restricting overflow admissions, enforcing strict compliance with escalated PPE, access to on-site free and frequent testing for staff, and testing all patients prior to hospital discharge and transfer to other facilities. CONCLUSIONS: Stringent infection control measures can prevent nosocomial COVID-19 transmission in healthcare facilities with high-risk patients during pandemic surges. These interventions were successful in ending these outbreaks.

Over-distension of the airways by mechanical ventilation in the elderly: adding insult to injury.

Setzer and colleagues demonstrate that older animals are more susceptible to ventilator-induced lung injury than young animals and develop a more pronounced local and systemic cytokine response to high tidal volumes. These data have significant implications for older patients receiving mechanical ventilation if these findings can be translated to human critical care medicine.

Surgeons' mental models of surgical site infection: Insights into adherence with complex prevention bundles.

Of 10 surgeons interviewed in a descriptive qualitative study, 6 believed that surgical site infections are inevitable. Bundle adherence was felt to be more likely with strong evidence-based measures developed by surgical leaders. The intrinsic desire to excel was viewed as the main adherence motivator, rather than "pay-for-performance" models.

Variability in infection surveillance methods and impact on surgical site infection rates.

BACKGROUND: The impact of variability in infection surveillance methodologies on publicly reported rates of surgical site infection (SSI) is not well defined. METHODS: We performed a cross-sectional study to assess infection preventionists' surveillance practices across acute care US hospitals. We collected self-reported annual facility standardized infection ratios for colon surgery and abdominal hysterectomy as provided by the National Healthcare Safety Network. Trend analysis using Kendall's rank correlation evaluated the association between surveillance rigor and SSI rates. RESULTS: Among 492 participating hospitals, 63%, 15%, 13%, and 8% were community, university-affiliated, critical access, and ambulatory surgical centers, respectively. Most critical access hospitals (82%) and ambulatory surgical centers (98%) reported less than one full time infection preventionists (P ≤ .001). University-affiliated medical centers spent significantly more time and used more data sources for monthly SSI review compared with other hospitals. Critical access hospitals and ambulatory surgical centers were more likely to rely on manual surveillance only (P < .001). The number of different data sources used for SSI surveillance was positively associated with higher SSI rates: (KT 0.14, P = .028 for colon SSI in 2017; KT 0.20, P = .009 for hysterectomy SSI in 2016; KT 0.25, P = .001 for hysterectomy SSI in 2017). CONCLUSIONS: Rigorous SSI surveillance using more data sources for case-finding is more likely to be associated with higher facility SSI rates for colon surgery and abdominal hysterectomy.

Hospital-acquired Legionella pneumonia outbreak at an academic medical center: Lessons learned.

BACKGROUND: An outbreak of Legionella pneumonia occurred at a university hospital using copper-silver ionization for potable water disinfection. We present the epidemiological and laboratory investigation of the outbreak, and associated case-control study. METHODS: Cases were defined by syndrome compatible with Legionella pneumonia with laboratory-confirmed Legionella infection. The water circuit and disinfection system were assessed, and water samples collected for Legionella culture. Whole genome multi-locus sequence typing (wgMLST) was used to compare the genetic similarity of patient and environmental isolates. A case-control study was conducted to identify risk factors for Legionella pneumonia. RESULTS: We identified 13 cases of hospital-acquired Legionella. wgMLST revealed >99.9% shared allele content among strains isolated from clinical and water samples. Smoking (P= .008), steroid use (P= .007), and documented shower during hospitalization (P= .03) were risk factors for Legionella pneumonia on multivariable analysis. Environmental assessment identified modifications to the hospital water system had occurred in the month preceding the outbreak. Multiple mitigation efforts and application of point of use water filters stopped the outbreak. CONCLUSIONS: Potable water system Legionella colonization occurs despite existing copper-silver ionization systems, particularly after structural disruptions. Multidisciplinary collaboration and direct monitoring for Legionella are important for outbreak prevention. Showering is a modifiable risk factor for nosocomial Legionella pneumonia. Shower restriction and point-of-use filters merit consideration during an outbreak.

Risk Factors and Mortality for Atypical Presentation of COVID-19 Infection in Hospitalized Patients - Lessons From the Early Pandemic.

OBJECTIVE: To assess the clinical epidemiology and outcomes of patients hospitalized with COVID-19 who did not experience fever and cough during the early pandemic. METHODS: Retrospective cohort of all patients admitted during March 13, 2020 through May 13, 2020 with laboratory-confirmed COVID-19 to 3 tertiary-care hospitals. Patient-level data (demographic, clinical manifestations, comorbid illnesses, inpatient treatment) were analyzed. The main outcome variable was atypical presentation, defined as any hospitalized patient with COVID-19 infection who did not experience both fever and cough. We identified risk factors for atypical presentation on univariate and multivariate analyses and assessed 30-day mortality differences via survival analysis. RESULTS: Of 163 patients in the study, 39 (24%) were atypical. On univariate analysis, atypical cases were significantly more likely to be older, reside in a long-term-care facility (LTCF), and have underlying diabetes mellitus, stroke, or cardiac disease; present without dyspnea or myalgia, have lower C-reactive proteins (CRP) and higher beta-natriuretic peptides. They were less likely to receive intensive care unit care or specific COVID-19 treatments (P < .05). The incidence of acute respiratory failure was not significantly different between the groups. On logistic regression, atypical cases were significantly more likely to be LTCF residents (P = 0.003) and have a lower average CRP (P = 0.01). Atypical cases had significantly higher 30-day mortality (hazard ratio 3.4 [95% CI, 1.6 - 7.2], P = 0.002). CONCLUSION: During the first pandemic surge, COVID-19 patients without inflammatory signs and symptoms were more likely to be LTCF residents and had higher mortality. Timely recognition of these atypical presentations may have prevented spread and improved clinical outcomes.

Gaining momentum in colorectal surgical site infection reduction through a human factors engineering approach.

Surgical site infection (SSI) prevention requires multiple interventions packaged into "bundles." The implementation of all bundle elements is key to the bundle's efficacy. A human-factors engineering approach can be used to identify key barriers and facilitators to implementing elements and develop recommendations for bundle implementation within the clinical work system.

The 2009 A/H1N1 pandemic influenza and the nursing home.

Seasonal and pandemic influenza clinically remain remarkably similar in long-term care populations. Clinicians cannot distinguish clinical influenza, whether seasonal or pandemic H1N1, from other respiratory viral infections in individual patients. Part of the difficulty in the clinical diagnosis relates to fewer clinical features that might help with diagnostic differentiation, such as fever. However, the nursing home provides an epidemiologic context that can prove helpful to clinicians who inquire--by considering illness patterns among others in the facility, both staff and residents. This can lead to more timely diagnosis and treatment in the resident, and prophylaxis--an opportunity to protect the remaining residents and staff. Check out the treatment guidelines posted on the CDC website to be sure to select the best agents, because antiviral resistance patterns have been rapidly changing.

Colorectal bundles for surgical site infection prevention: A systematic review and meta-analysis.

OBJECTIVE: In colorectal surgery, the composition of the most effective bundle for prevention of surgical site infections (SSI) remains uncertain. We performed a meta-analysis to identify bundle interventions most associated with SSI reduction. METHODS: We systematically reviewed 4 databases for studies that assessed bundles with ≥3 elements recommended by clinical practice guidelines for adult colorectal surgery. The main outcome was 30-day postoperative SSI rate (overall, superficial, deep, and/or organ-space). RESULTS: We included 40 studies in the qualitative review, and 35 studies (54,221 patients) in the quantitative review. Only 3 studies were randomized controlled trials. On meta-analyses, bundles were associated with overall SSI reductions of 44% (RR, 0.57; 95% CI, 0.48-0.65); superficial SSI reductions of 44% (RR, 0.56; 95% CI, 0.42-0.75); deep SSI reductions of 33% (RR, 0.67; 95% CI, 0.46-0.98); and organ-space SSI reductions of 37% (RR, 0.63; 95% CI, 0.50-0.81). Bundle composition was heterogeneous. In our meta-regression analysis, bundles containing ≥11 elements, consisting of both standard of care and new interventions, demonstrated the greatest SSI reduction. Separate instrument trays, gloves with and without gown change for wound closure, and standardized postoperative dressing change at 48 hours correlated with the highest reductions in superficial SSIs. Mechanical bowel preparation combined with oral antibiotics, and preoperative chlorhexidine showers correlated with highest organ-space SSI reductions. CONCLUSIONS: Preventive bundles emphasizing guideline-recommended elements from both standard of care as well as new interventions were most effective for SSI reduction following colorectal surgery. High clinical-bundle heterogeneity and low quality for most observational studies significantly limit our conclusion.

COVID-19: An Emerging Threat to Antibiotic Stewardship in the Emergency Department.

While current research efforts focus primarily on identifying patient level interventions that mitigate the direct impact of COVID-19, it is important to consider the collateral effects of COVID-19 on antimicrobial resistance. Early reports suggest high rates of antibiotic utilization in COVID-19 patients despite their lack of direct activity against viral pathogens. The ongoing pandemic is exacerbating known barriers to optimal antibiotic stewardship in the ED, representing an additional direct threat to patient safety and public health. There is an urgent need for research analyzing overall and COVID-19 specific antibiotic prescribing trends in the ED. Optimizing ED stewardship during COVID-19 will likely require a combination of traditional stewardship approaches (e.g. academic detailing, provider education, care pathways) and effective implementation of host response biomarkers and rapid COVID-19 diagnostics. Antibiotic stewardship interventions with demonstrated efficacy in mitigating the impact of COVID-19 on ED prescribing should be widely disseminated and inform the ongoing pandemic response.

Clinical review: primary influenza viral pneumonia.

Primary influenza pneumonia has a high mortality rate during pandemics, not only in immunocompromised individuals and patients with underlying comorbid conditions, but also in young healthy adults. Clinicians should maintain a high index of suspicion for this diagnosis in patients presenting with influenza-like symptoms that progress quickly (2 to 5 days) to respiratory distress and extensive pulmonary involvement. The sensitivity of rapid diagnostic techniques in identifying infections with the pandemic 2009 H1N1v influenza strain is currently suboptimal. The most reliable real-time reverse transcriptase-polymerase chain reaction molecular testing is available in limited clinical settings. Despite 6 months of pandemic circulation, most novel H1N1v pandemic strains remain susceptible to oseltamivir. Ensuring an appropriate oxygenation and ventilation strategy, as well as prompt initiation of antiviral therapy, is essential in management.

Pre-operative Decolonization as a Strategy to Reduce Surgical Site Infection.

PURPOSE OF REVIEW: To identify the most common strategies currently used for S. aureus decolonization and surgical site infection (SSI) prevention. RECENT FINDINGS: Pre-operative colonization with Staphylococcus aureus increases SSI risk. Screening and decolonization with intra-nasal mupirocin and pre-operative chlorhexidine bathing remains the most common and effective strategy, especially for orthopedic and cardiovascular surgery. Intra-nasal povidone-iodine immediately before surgery appears effective in preliminary studies, is less expensive, and may be easier to implement in the clinical setting. Future well-designed clinical research studies are needed to confirm its effectiveness in SSI prevention. Intra-nasal alcohol-based antisepsis and photodynamic therapy are promising strategies that deserve further study before they can be clinically applied to SSI prevention. Decolonization with intra-nasal mupirocin or povidone-iodine, in addition to pre-operative chlorhexidine bathing, is an important SSI prevention strategy. Future studies should address optimal dosing, timing, and number of applications for each regimen.

Cefazolin as surgical antimicrobial prophylaxis in hysterectomy: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Current practice guidelines recommend cefazolin, cefoxitin, cefotetan, or ampicillin-sulbactam as first-line antibiotic prophylaxis in hysterectomy. We undertook this systematic review and meta-analysis of randomized controlled trials (RCTs) to determine whether cefazolin, with limited antianaerobic spectrum, is as effective in preventing surgical site-infection (SSI) as the other first-choice antimicrobials that have more extensive antianaerobic activity. METHODS: We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for relevant randomized controlled trials (RCT) in any language up to January 23, 2018. We only included trials that measured SSI (our primary outcome) defined as superficial, deep, or organ space. We excluded trials of ß-lactams no longer in clinical use. RESULTS: In terms of SSI incidence, cefazolin use was not inferior to its comparator in 12 of 13 individual RCTs included in the analysis. The meta-analysis summary estimate showed a significantly higher SSI risk with cefazolin versus cefoxitin or cefotetan (risk ratio, 1.7; 95% CI, 1.04-2.77; P = .03). However, most studies included nonstandardized dosing and duration of antimicrobial prophylaxis, had indeterminate or high risk of bias, did not include patients with gynecological malignancies, and/or were older RCTs not reflective of current clinical practices. CONCLUSION: Due to inherent limitations associated with old RCTs with limited relevance to contemporary surgery, an RCT of cefazolin versus regimens with significant antianaerobic spectrum is needed to establish the optimal choice for SSI prevention in hysterectomy.

Efficacy and safety of a novel antimicrobial preoperative skin preparation.

OBJECTIVE: Alternatives to skin preparation with conventional preoperative antiseptics are required because of adverse reactions and the potential emergence of resistance. Here, we present 2 phase 2 studies of ZuraGard (ZG), a novel formulation of isopropyl alcohol and functional excipients developed for preoperative skin antisepsis. METHODS: Microbial skin flora on abdominal and inguinal sites in healthy volunteers were quantitatively assessed following application of ZG versus a negative control (ZV) and a chlorhexidine/alcohol preparation, Chloraprep (CP). In trial 1, ZG administered for both recommended and abbreviated application times was compared with CP and ZV via bacterial reductions at 10 minutes, and 6 hours, 12 hours, and 24 hours following application. In trial 2, the 10-minute postapplication responder rates (RRs) for ZG, participants with abdominal ≥2 log10 per cm2, and inguinal ≥3 log10 per cm2 reductions in colony-forming units (CFU) were compared to RRs of participants treated with CP. RESULTS: In trial 1, ZG at the recommended application time reduced mean bacterial counts by ~3.18 log10 CFU/cm2 and ~2.98 log10 CFU/cm2 at abdominal and inguinal sites, respectively. Qualitatively similar reductions were observed for the abbreviated ZG application time and all CP applications. Application of ZV was ineffective. In trial 2, 10-minute RRs for ZG and CP exceeded 90% at abdominal sites. At inguinal sites, RRs were 83.3% for ZG and 86.7% for CP. No skin irritation or other adverse events were observed. CONCLUSIONS: ZG matched CP efficacy under these experimental conditions with immediate and persistent microbial reductions, including abbreviated application times. Further clinical studies of this novel preoperative antiseptic are merited.

Clostridium difficile: the increasingly difficult pathogen.

The epidemiology of Clostridium difficile infection is changing as a result of the epidemic spread of the hypervirulent North American Pulsefield type 1 strain. Clinicians are likely to encounter this disease more frequently than ever in their practice, and should be familiar with the updates in its diagnosis and treatment.