Vancomycin-resistant enterococci colonization–infection model: parameter impacts and outbreak risks

Vancomycin-resistant enterococci (VRE) infections have been linked to increased mortality and costs. A new model of a VRE-infested intensive care unit (ICU) is introduced. It incorporates critical features including the difference between colonization and infection, the role of special preventive care treatment cycles, fitness cost, and antibiotic use. Five patient stages are considered: susceptible, colonized with and without special preventive care, and infected with and without treatment. Parameter ranges are determined representing different ICUs and incorporated to numerically simulate the model. Basic reproductive number of the infection is derived and the impacts of the parameters are analysed. Strategies to minimize VRE infections and outbreak risk are explored with a focus on efficient and simultaneous control of critical parameters. In particular, threshold values of the level of special preventive care and ICU compliance rate are given to achieve desired goals under various constraints.     

Risk factors for vancomycin-resistant enterococci colonisation in critically ill patients

Vancomycin-resistant enterococci (VRE) are important hospital pathogens and have become increasingly common in patients admitted to the intensive care unit (ICU). To determine the incidence and the risk factors associated with VRE colonisation among ICU patients, active surveillance cultures for VRE faecal carriages were carried out in patients admitted to the ICU of the University Hospital of Uberlandia, Minas Gerais, Brazil. Risk factors were assessed using a case-control study. Seventy-seven patients (23.1%) were found to be colonised with vanC VRE and only one patient (0.3%) was colonised with vanA VRE. Independent risk factors for VRE colonisation included nephropathy [odds ratio (OR) = 13.6, p < 0.001], prior antibiotic use (OR = 5.5, p < 0.03) and carbapenem use (OR = 17.3, p < 0.001). Our results showed a higher frequency (23.1%) of Enterococcus gallinarum and Enterococcus casseliflavus, species that are intrinsically resistant to low levels of vancomycin (vanC), without an associated infection, associated with prior antibiotic use, carbapenem use and nephropathy as comorbidity. This study is the first to demonstrate the risk factors associated with vanC VRE colonisation in ICU hospitalised patients. Although vanA and vanB enterococci are of great importance, the epidemiology of vanC VRE needs to be better understood. Even though the clinical relevance of vanC VRE is uncertain, these species are opportunistic pathogens and vanC VRE-colonised patients are a potential epidemiologic reservoir of resistance genes.     

Incidence of and Risk Factors for Infection or Colonization of Vancomycin-Resistant Enterococci in Patients in the Intensive Care Unit

The prevalence of vancomycin-resistant enterococci (VRE) colonization or infection in the hospital setting has increased globally. Many previous studies had analysed the risk factors for acquiring VRE, based on cross-sectional studies or prevalent cases. However, the actual incidence of and risk factors for VRE remain unclear. The present study was conducted in order to clarify the incidence of and risk factors for VRE in the intensive care unit (ICU). From 1^st April 2008 to 31^st March 2009, all patients admitted to a surgical ICU (SICU) were put on active surveillance for VRE. The surveillance cultures, obtained by rectal swab, were taken on admission, weekly while staying in the SICU, and on discharge from the SICU. A total of 871 patients were screened. Among them, 34 were found to carry VRE before their admission to the SICU, and 47 acquired VRE during their stay in the SICU, five of whom developed VRE infections. The incidence of newly acquired VRE during ICU stay was 21.9 per 1000 patient-days (95% confidence interval [CI], 16.4–29.1). Using multivariate analysis by logistic regression, we found that the length of ICU stay was an independent risk factor for new acquisition of VRE. In contrast, patients with prior exposure to first-generation cephalosporin were significantly less likely to acquire VRE. Strategies to reduce the duration of ICU stay and prudent usage of broad-spectrum antibiotics are the keys to controlling VRE transmission.     

Respiratory nosocomial infections in the medical intensive care unit

Intensive care unit (ICU)-acquired lower respiratory tract infections include acute tracheobronchitis and hospital-acquired and ventilator-associated pneumonia (VAP). Nosocomial pneumonia is the second most common hospital-acquired infection and the leading cause of death in hospital-acquired infections. The mortality rate in VAP ranges from 24% to 76% in several studies. ICU ventilated patients with VAP have a 2- to 10-fold higher risk of death than patients without it. Early oropharyngeal colonization is pivotal in the etiopathogenesis of VAP. The knowledge of risk factors for VAP is important in developing effective preventive programs. Once the physician decides to treat a suspected episode of ICU-acquired pneumonia, some issues should be kept on mind: first, the adequacy of the initial empiric antibiotic therapy; second, the modification of initial inadequate therapy according to microbiological results; third, the benefit of combination therapy; and finally, the duration of the antimicrobial treatment. Additionally, a protocolized work-up to identify the causes of non-response to treatment is mandatory. All these issues are discussed in depth in this article.     

Can Interactions between Timing of Vaccine-Altered Influenza Pandemic Waves and Seasonality in Influenza Complications Lead to More Severe Outcomes?

Vaccination can delay the peak of a pandemic influenza wave by reducing the number of individuals initially susceptible to influenza infection. Emerging evidence indicates that susceptibility to severe secondary bacterial infections following a primary influenza infection may vary seasonally, with peak susceptibility occurring in winter. Taken together, these two observations suggest that vaccinating to prevent a fall pandemic wave might delay it long enough to inadvertently increase influenza infections in winter, when primary influenza infection is more likely to cause severe outcomes. This could potentially cause a net increase in severe outcomes. Most pandemic models implicitly assume that the probability of severe outcomes does not vary seasonally and hence cannot capture this effect. Here we show that the probability of intensive care unit (ICU) admission per influenza infection in the 2009 H1N1 pandemic followed a seasonal pattern. We combine this with an influenza transmission model to investigate conditions under which a vaccination program could inadvertently shift influenza susceptibility to months where the risk of ICU admission due to influenza is higher. We find that vaccination in advance of a fall pandemic wave can actually increase the number of ICU admissions in situations where antigenic drift is sufficiently rapid or where importation of a cross-reactive strain is possible. Moreover, this effect is stronger for vaccination programs that prevent more primary influenza infections. Sensitivity analysis indicates several mechanisms that may cause this effect. We also find that the predicted number of ICU admissions changes dramatically depending on whether the probability of ICU admission varies seasonally, or whether it is held constant. These results suggest that pandemic planning should explore the potential interactions between seasonally varying susceptibility to severe influenza outcomes and the timing of vaccine-altered pandemic influenza waves.     

Immune modulation in the treatment of respiratory infection

The limitations of currently available treatment for severe respiratory infection are demonstrated by the relatively fixed mortality associated with these infections despite advances in nutrition, vaccines, antibiotics, and critical care. This might be due in part to the changing spectrum of pathogens and development of drug resistance. Cytokines are potent molecules that function as growth factors and orchestrate both innate and adaptive immune responses. Several of these factors have entered the clinical arena to support or augment the immune response. Moreover, the use of cytokines has recently been expanded to patients without an overtly defective immune system but who have either significant infection or infection with drug resistant organisms. The use of cytokines as adjuvants in the treatment of respiratory infections is reviewed.     

重症监护室烧伤感染患者脓毒症的病原菌分布及影响因素研究

目的:探讨重症监护室(ICU)烧伤感染患者脓毒症的发生情况及病原菌分布,并分析其危险因素,为防治ICU烧伤感染患者脓毒症提供理论依据。方法:收集我院2016年7月-2019年7月期间的86例ICU烧伤感染患者的临床资料,依据是否发生脓毒症,将其分为脓毒症组和非脓毒症组,比较两组的基本资料等情况,分析ICU烧伤感染患者脓毒症的发生率及病原菌分布,并分析ICU烧伤感染患者脓毒症发生的影响因素。结果:86例ICU烧伤感染患者中有33例发生脓毒症,发生率为38.37%;ICU烧伤感染患者脓毒症病原菌主要是革兰阴性杆菌(占54.55%),其次是革兰阳性球菌(占42.42%);单因素结果分析发现,烧伤至入院时间、合并糖尿病、吸入性损伤、首次手术时间以及烧伤面积与ICU烧伤感染患者脓毒症的发生有关(P<0.05);多因素Logistic回归分析发现,首次手术时间>2d、TBSA>50%是ICU烧伤感染患者脓毒症发生的独立危险因素(P<0.05)。结论:ICU烧伤感染患者易发生脓毒症,首次手术时间>2d以及TBSA>50%是其发生的独立危险因素,临床应采取针对性预防措施,以降低ICU烧伤感染患者脓毒症发生率。     

Marginal structural models for partial exposure regimes

Intensive care unit (ICU) patients are highly susceptible to hospital-acquired infections due to their poor health and many invasive therapeutic treatments. The effect on mortality of acquiring such infections is, however, poorly understood. Our goal is to quantify this using data from the National Surveillance Study of Nosocomial Infections in ICUs (Belgium). This is challenging because of the presence of time-dependent confounders, such as mechanical ventilation, which lie on the causal path from infection to mortality. Standard statistical analyses may be severely misleading in such settings and have shown contradictory results. Inverse probability weighting for marginal structural models may instead be used but is not directly applicable because these models parameterize the effect of acquiring infection on a given day in ICU, versus "never" acquiring infection in ICU, and this is ill-defined when ICU discharge precedes that day. Additional complications arise from the informative censoring of the survival time by hospital discharge and the instability of the inverse weighting estimation procedure. We accommodate this by introducing a new class of marginal structural models for so-called partial exposure regimes. These describe the effect on the hazard of death of acquiring infection on a given day s, versus not acquiring infection "up to that day," had patients stayed in the ICU for at least s days.     

Calcium orthophosphate-based bone cements (CPCs): Applications, antibiotic release and alternatives to antibiotics

Calcium orthophosphate bone cements (CPCs) are widely used in orthopedic surgery. Implants are highly susceptible to infection and often lead to the formation of microbial biofilms. Antibiotics are often incorporated into bone cement to prevent infection. The increase in the number of microorganisms acquiring or developing resistance to antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), is a major concern. Bacteriocins (antimicrobial peptides) offer an alternative to antibiotics. Their mode of activity involves permanent destabilization of the plasma membrane of target cells. A number of broad-spectrum bacteriocins produced by lactic acid bacteria and Bacillus spp. have recently been reported. In this REVIEW the major characteristics of calcium phosphate bone cements, prosthetic joint-associated infections, and treatment of these infections is discussed. The role of antimicrobial agents in CPCs is discussed and the possibility of incorporating bacteriocins in prosthetic devices is investigated.     

Infection-age structured epidemic models with behavior change or treatment

We formulate infection-age structured susceptible-infective-removed (SIR) models with behavior change or treatment of infections. Individuals change their behavior or have treatment after they are infected. Using infection age as a continuous variable, and dividing infectives into discrete groups with different infection stages, respectively, we formulate a partial differential equation model and an ordinary differential equation model with behavior change or treatment. We derive explicit formulas for the reproductive number by linear stability analysis of the infection-free equilibrium, and explicit formulas for the unique endemic equilibrium, when it exists, for both models. These formulas provide mathematical theoretical frameworks for analysis of impact of behavior change or treatment of infection to the transmission dynamics of infectious diseases. We study several special cases and provide sensitivity analysis for the reproductive numbers with respect to model parameters based on those formulas.     

Infection-age structured epidemic models with behavior change or treatment

We formulate infection-age structured susceptible-infective-removed (SIR) models with behavior change or treatment of infections. Individuals change their behavior or have treatment after they are infected. Using infection age as a continuous variable, and dividing infectives into discrete groups with different infection stages, respectively, we formulate a partial differential equation model and an ordinary differential equation model with behavior change or treatment. We derive explicit formulas for the reproductive number by linear stability analysis of the infection-free equilibrium, and explicit formulas for the unique endemic equilibrium, when it exists, for both models. These formulas provide mathematical theoretical frameworks for analysis of impact of behavior change or treatment of infection to the transmission dynamics of infectious diseases. We study several special cases and provide sensitivity analysis for the reproductive numbers with respect to model parameters based on those formulas.     

Examining the impact of ICU population interaction structure on modeled colonization dynamics of Staphylococcus aureus

BackgroundComplex transmission models of healthcare-associated infections provide insight for hospital epidemiology and infection control efforts, but they are difficult to implement and come at high computational costs. Structuring more simplified models to incorporate the heterogeneity of the intensive care unit (ICU) patient-provider interactions, we explore how methicillin-resistant Staphylococcus aureus (MRSA) dynamics and acquisitions may be better represented and approximated.MethodsUsing a stochastic compartmental model of an 18-bed ICU, we compared the rates of MRSA acquisition across three ICU population interaction structures: a model with nurses and physicians as a single staff type (SST), a model with separate staff types for nurses and physicians (Nurse-MD model), and a Metapopulation model where each nurse was assigned a group of patients. The proportion of time spent with the assigned patient group (γ) within the Metapopulation model was also varied.ResultsThe SST, Nurse-MD, and Metapopulation models had a mean of 40.6, 32.2 and 19.6 annual MRSA acquisitions respectively. All models were sensitive to the same parameters in the same direction, although the Metapopulation model was less sensitive. The number of acquisitions varied non-linearly by values of γ, with values below 0.40 resembling the Nurse-MD model, while values above that converged toward the Metapopulation structure.DiscussionInclusion of complex population interactions within a modeled hospital ICU has considerable impact on model results, with the SST model having more than double the acquisition rate of the more structured metapopulation model. While the direction of parameter sensitivity remained the same, the magnitude of these differences varied, producing different colonization rates across relatively similar populations. The non-linearity of the model’s response to differing values of a parameter gamma (γ) suggests simple model approximations are appropriate in only a narrow space of relatively dispersed nursing assignments.ConclusionSimplifying assumptions around how a hospital population is modeled, especially assuming random mixing, may overestimate infection rates and the impact of interventions. In many, if not most, cases more complex models that represent population mixing with higher granularity are justified.     

MRSA与VRE的快速检查方法的研究进展

MRSA与VRE在医院获得性感染中检出率的不断增加给临床治疗由此菌引起的感染性疾病带来了严峻的挑战,因此迅速隔离带菌者,防止院内感染的传播,提高治疗效果至关重要。本文旨在综述能直接从患者的送检原样本中检出MRSA和VRE的快速诊断试验的研究。     

新建ICU病区医院感染调查分析

目的了解新建ICU病区启用后患者医院感染状况,探讨其流行菌株和易感因素,为预防和控制医院感染提供参考。方法对2005年1月至2006年6月新建ICU病区的患者和环境进行了流行病学调查分析。结果新ICU病区患者医院感染率为36.7%。所有病原菌中鲍氏不动杆菌占28.2%,金黄色葡萄球菌占20.5%,铜绿假单胞菌占15.4%。且环境中空气、陪护人员手、医护人员鼻前庭等亦培养出鲍氏不动杆菌和金黄色葡萄球,药敏显示各菌耐药水平较高。结论医院必须加强室内外环境和空气监控,防止交叉感染,严格无菌侵入性操作和抗生素的使用原则,从而有效减少医院感染的发生。     

Nosocomial infection caused by vancomycin‐susceptible multidrug‐resistant Enterococcus faecalis over a long period in a university hospital in Japan

Compared with other developed countries, vancomycin‐resistant enterococci (VRE) are not widespread in clinical environments in Japan. There have been no VRE outbreaks and only a few VRE strains have sporadically been isolated in our university hospital in Gunma, Japan. To examine the drug susceptibility of Enterococcus faecalis and nosocomial infection caused by non‐VRE strains, a retrospective surveillance was conducted in our university hospital. Molecular epidemiological analyses were performed on 1711 E. faecalis clinical isolates collected in our hospital over a 6‐year period [1998–2003]. Of these isolates, 1241 (72.5%) were antibiotic resistant and 881 (51.5%) were resistant to two or more drugs. The incidence of multidrug resistant E. faecalis (MDR‐Ef) isolates in the intensive care unit increased after enlargement and restructuring of the hospital. The major group of MDR‐Ef strains consisted of 209 isolates (12.2%) resistant to the five drug combination tetracycline/erythromycin/kanamycin/streptomycin/gentamicin. Pulsed‐field gel electrophoresis analysis of the major MDR‐Ef isolates showed that nosocomial infections have been caused by MDR‐Ef over a long period (more than 3 years). Multilocus sequence typing showed that these strains were mainly grouped into ST16 (CC58) or ST64 (CC8). Mating experiments suggested that the drug resistances were encoded on two conjugative transposons (integrative conjugative elements), one encoded tetracycline‐resistance and the other erythromycin/kanamycin/streptomycin/gentamicin‐resistance. To our knowledge, this is the first report of nosocomial infection caused by vancomycin‐susceptible MDR‐Ef strains over a long period in Japan.     

Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention

Multidrug-resistant bacteria are the cause of an increasing number of deadly pulmonary infections. Because there is currently a paucity of novel antibiotics, phage therapy--the use of specific viruses that infect bacteria--is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose) administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose) resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. This work provides an incentive to develop clinical studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung infections.     

Critical Care Needs in Patients with Diffusion-Weighted Imaging Negative MRI after tPA - Does One Size Fit All?

MethodsA retrospective chart review was performed for 209 patients who received IV tPA for acute stroke. Data on stroke risk factors, physiologic parameters, stroke severity, MRI characteristics, and final diagnosis were collected. The timing and nature of ICU interventions, if needed, was recorded. Multivariable logistic regression was used to determine factors associated with subsequent ICU needs.ResultsPatients with cerebral infarct on MRI after tPA had over 9 times higher odds of requiring ICU care compared to patients with DWI negative MRI (OR 9.2, 95% CI 2.49–34.15). All DWI negative patients requiring ICU care did so by the end of tPA infusion (p = 0.006). Among patients with DWI negative MRI, need for ICU interventions was associated with higher NIH Stroke Scale (NIHSS) scores (p<0.001), uncontrolled hypertension (p<0.001), seizure at onset (p = 0.002), and reduced estimated glomerular filtration rate (eGFR) (p = 0.010).ConclusionsOnly a small number of DWI negative patients required ICU care. In patients without critical care needs by the end of thrombolysis, post-tPA MRI may be considered for triaging DWI negative patients to a less resource intense monitoring environment.     

Application of control measures for infections caused by multi-resistant gram-negative bacteria in intensive care unit patients

Multi-resistant gram-negative rods are important pathogens in intensive care units (ICU), cause high rates of mortality, and need infection control measures to avoid spread to another patients. This study was undertaken prospectively with all of the patients hospitalized at ICU, Anesthesiology of the Hospital S?o Paulo, using the ICU component of the National Nosocomial Infection Surveillance System (NNIS) methodology, between March 1, 1997 and June 30, 1998. Hospital infections occurring during the first three months after the establishment of prevention and control measures (3/1/97 to 5/31/97) were compared to those of the last three months (3/1/98 to 5/31/98). In this period, 933 NNIS patients were studied, with 139 during the first period and 211 in the second period. The overall rates of infection by multi-resistant microorganisms in the first and second periods were, respectively, urinary tract infection: 3.28/1000 patients/day; 2.5/1000 patients/day; pneumonia: 2.10/1000 patients/day; 5.0/1000 patients/day; bloodstream infection: 1.09/1000 patients/day; 2.5/1000 patients/day. A comparison between overall infection rates of both periods (Wilcoxon test) showed no statistical significance (p = 0.067). The use of intervention measures effectively decreased the hospital bloodstream infection rate (p < 0.001), which shows that control measures in ICU can contribute to preventing hospital infections.     

Fungal Infections in COVID-19 Intensive Care Patients

Opportunistic fungal infections increase morbidity and mortality in COVID-19 patients monitored in intensive care units (ICU). As patients’ hospitalization days in the ICU and intubation period increase, opportunistic infections also increase, which prolongs hospital stay days and elevates costs. The study aimed to describe the profile of fungal infections and identify the risk factors associated with mortality in COVID-19 intensive care patients. The records of 627 patients hospitalized in ICU with the diagnosis of COVID-19 were investigated from electronic health records and hospitalization files. The demographic characteristics (age, gender), the number of ICU hospitalization days and mortality rates, APACHE II scores, accompanying diseases, antibiotic-steroid treatments taken during hospitalization, and microbiological results (blood, urine, tracheal aspirate samples) of the patients were recorded. Opportunistic fungal infection was detected in 32 patients (5.10%) of 627 patients monitored in ICU with a COVID-19 diagnosis. The average APACHE II score of the patients was 28 ± 6. While 25 of the patients (78.12%) died, seven (21.87%) were discharged from the ICU. Candida parapsilosis (43.7%) was the opportunistic fungal agent isolated from most blood samples taken from COVID-19 positive patients. The mortality rate of COVID-19 positive patients with candidemia was 80%. While two out of the three patients (66.6%) for whom fungi were grown from their tracheal aspirate died, one patient (33.3%) was transferred to the ward. Opportunistic fungal infections increase the mortality rate of COVID-19-positive patients. In addition to the risk factors that we cannot change, invasive procedures should be avoided, constant blood sugar regulation should be applied, and unnecessary antibiotics use should be avoided.     

Mini-review: Antimicrobial central venous catheters – recent advances and strategies

Central venous catheters (CVCs) nowadays constitute critical devices used in medical care, namely in intensive care units. However, CVCs also represent one of the indwelling medical devices with enhanced risk of nosocomial device-related infection. Catheter-related infections (CRIs) are a major cause of patient morbidity and mortality, often justifying premature catheter removal and an increase in costs and use of resources. Adhesion and subsequent biofilm formation on the surfaces of indwelling catheters is elemental to the onset of pathogenesis. Seeking the prevention of CVC colonisation and CRI, a variety of approaches have been studied, tested and, in some cases, already applied in clinical practice. This review looks at the current preventive strategies often used to decrease the risk of CRIs due to colonization and biofilm formation on catheter surfaces, as well as at the more recent approaches under investigation.