The epidemiology of nonventilator hospital-acquired pneumonia in the United States.

BACKGROUND: Nonventilator hospital-acquired pneumonia (NV-HAP) is among the most common hospital-acquired infections. The purpose of our study was to quantify the incidence and influence of NV-HAP in the United States using a national dataset. METHODS: The 2012 US National Inpatient Sample dataset was used to compare an NV-HAP group to 4 additional group cohorts: pneumonia on admission, general hospital admissions, matched on mortality and disease severity, and ventilator-associated pneumonia (VAP). The main outcome was NV-HAP incidence. The secondary outcome was to compare hospital length of stay, total hospital charges, and mortality between the NV-HAP group and the 4 additional group cohorts. RESULTS: The overall incidence of NV-HAP was 1.6%, which represents a rate of 3.63 per 1,000 patient-days. NV-HAP was associated with increased total hospital charges, a longer hospital length of stay, and greater likelihood of death in comparison to all groups except patients with VAP. CONCLUSION: NV-HAP is an underappreciated and serious patient safety issue, resulting in significant increases in cost, length of stay, and mortality. Efforts toward prevention of NV-HAP should be raised to the same level of concern as VAP prevention.

Suffer the Infants: A Severe Case of Pertussis in Oregon, 2012.

Pertussis remains a public health concern in Oregon, especially among young infants. The disease can be severe in this age group and is associated with a high inpatient cost. This report describes an Oregon infant who was hospitalized with pertussis for 90 days, required extracorporeal oxygenation for 43 days, suffered complications including stroke, and had hospital charges totaling $1.5 million. Pertussis morbidity among young infants argues for vaccination of women during each pregnancy and of infants beginning promptly at two months of age.

Clinical pharmacological approach for balancing the use of daptomycin and linezolid in comparison with that of vancomycin in the treatment of MRSA-related infections.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most challenging bacterial pathogens responsible for severe infections among hospitalized patients. In recent years there is increasing evidence that the clinical efficacy of vancomycin is progressively decreasing. Although daptomycin and linezolid are valuable alternatives to vancomycin for the treatment of MRSA-related bloodstream infections and pneumonia, respectively, a great deal of debate exists about their role in daily clinical practice due to cost-effectiveness issues. In this article we put into perspective the importance of pharmacokinetic/pharmacodynamic (PK/PD) considerations based on recent experimental and clinical data to argue whether they could be helpful in identifying clinical conditions in which these agents could be advantageous as compared to vancomycin.

Overview of community-acquired pneumonia and the role of inflammatory mechanisms in the immunopathogenesis of severe pneumococcal disease.

Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality among the infectious diseases. Despite the implementation of national pneumococcal polyvalent vaccine-based immunisation strategies targeted at high-risk groups, Streptococcus pneumoniae (the pneumococcus) remains the most common cause of CAP. Notwithstanding the HIV pandemic, major challenges confronting the control of CAP include the range of bacterial and viral pathogens causing this condition, the ever-increasing problem of antibiotic resistance worldwide, and increased vulnerability associated with steadily aging populations in developed countries. These and other risk factors, as well as diagnostic strategies, are covered in the first section of this review. Thereafter, the review is focused on the pneumococcus, specifically the major virulence factors of this microbial pathogen and their role in triggering overexuberant inflammatory responses which contribute to the immunopathogenesis of invasive disease. The final section of the review is devoted to a consideration of pharmacological, anti-inflammatory strategies with adjunctive potential in the antimicrobial chemotherapy of CAP. This is focused on macrolides, corticosteroids, and statins with respect to their modes of anti-inflammatory action, current status, and limitations.

Bacterial pneumonias during an influenza pandemic: how will we allocate antibiotics?

We are currently in the midst of the 2009 H1N1 pandemic, and a second wave of flu in the fall and winter could lead to more hospitalizations for pneumonia. Recent pathologic and historic data from the 1918 influenza pandemic confirms that many, if not most, of the deaths in that pandemic were a result of secondary bacterial pneumonias. This means that a second wave of 2009 H1N1 pandemic influenza could result in a widespread shortage of antibiotics, making these medications a scarce resource. Recently, our University of Michigan Health System (UMHS) Scarce Resource Allocation Committee (SRAC) added antibiotics to a list of resources (including ventilators, antivirals, vaccines) that might become scarce during an influenza pandemic. In this article, we summarize the data on bacterial pneumonias during the 1918 influenza pandemic, discuss the possible impact of a pandemic on the University of Michigan Health System, and summarize our committee's guiding principles for allocating antibiotics during a pandemic.

Risk assessment of Pseudomonas aeruginosa in water.

P. aeruginosa is part of a large group of free-living bacteria that are ubiquitous in the environment. This organism is often found in natural waters such as lakes and rivers in concentrations of 10/100 mL to >1,000/100 mL. However, it is not often found in drinking water. Usually it is found in 2% of samples, or less, and at concentrations up to 2,300 mL(-1) (Allen and Geldreich 1975) or more often at 3-4 CFU/mL. Its occurrence in drinking water is probably related more to its ability to colonize biofilms in plumbing fixtures (i.e., faucets, showerheads, etc.) than its presence in the distribution system or treated drinking water. P. aeruginosa can survive in deionized or distilled water (van der Jooij et al. 1982; Warburton et al. 1994). Hence, it may be found in low nutrient or oligotrophic environments, as well as in high nutrient environments such as in sewage and in the human body. P. aeruginosa can cause a wide range of infections, and is a leading cause of illness in immunocompromised individuals. In particular, it can be a serious pathogen in hospitals (Dembry et al. 1998). It can cause endocarditis, osteomyelitis, pneumonia, urinary tract infections, gastrointestinal infections, and meningitis, and is a leading cause of septicemia. P. aeruginosa is also a major cause of folliculitis and ear infections acquired by exposure to recreational waters containing the bacterium. In addition, it has been recognized as a serious cause of keratitis, especially in patients wearing contact lenses. P. aeruginosa is also a major pathogen in burn and cystic fibrosis (CF) patients and causes a high mortality rate in both populations (MOlina et al. 1991; Pollack 1995). P. aeruginosa is frequently found in whirlpools and hot tubs, sometimes in 94-100% of those tested at concenrations of <1 to 2,400 CFU/mL. The high concentrations found probably result from the relatively high temperatures of whirlpools, which favor the growth of P. aeruginosa, and the aeration which also enhances its growth. The organism is usually found in whirlpools when the chlorine concentrations are low, but it has been isolated even in the presence of 3.00 ppm residual free chlorine (Price and Ahearn 1988). Many outbreaks of folliculitis and ear infections have been reportedly associated with the use of whirlpools and hot tubs that contain P. aeruginosa (Ratnam et al. 1986). Outbreaks have also been reported from exposure to P. aeruginosa in swimming pools and water slides. Although P. aeruginosa has a reputation for being resistant to disinfection, most studies show that it does not exhibit any marked resistance to the disinfectants used to treat drinking water such as chlorine, chloramines, ozone, or iodine. One author, however, did find it to be slightly more resistant to UV disinfection than most other bacteria (Wolfe 1990). Although much has been written about biofilms in the drinking water industry, very little has been reported regarding the role of P. aeruginosa in biofilms. Tap water appears to be a significant route of transmission in hospitals, from colonization of plumbing fixtures. It is still not clear if the colonization results from the water in the distribution system, or personnel use within the hospital. Infections and colonization can be significantly reduced by placement of filters on the water taps. The oral dose of P. aeruginosa required to establish colonization in a healthy subject is high (George et al. 1989a). During dose-response studies, even when subjects (mice or humans) were colonized via ingestion, there was no evidence of disease. P. aeruginosa administered by the aerosol route at levels of 10(7) cells did cause disease symptoms in mice, and was lethal in aerosolized doses of 10(9) cells. Aerosol dose-response studies have not been undertaken with human subjects. Human health risks associated with exposure to P. aeruginosa via drinking water ingestion were estimated using a four-step risk assessment approach. The risk of colonization from ingesting P. aeruginosa in drinking water is low. The risk is slightly higher if the subject is taking an antibiotic resisted by P. aeruginosa. The fact that individuals on ampicillin are more susceptible to Pseudomonas gastrointestinal infection probably results from suppression of normal intestinal flora, which would allow Pseudomonas to colonize. The process of estimating risk was significantly constrained because of the absence of specific (quantitative) occurrence data for Pseudomonas. Sensitivity analysis shows that the greatest source of variability/uncertainty in the risk assessment is from the density distribution in the exposure rather than the dose-response or water consumption distributions. In summary, two routes appear to carry the greatest health risks from contacting water contaminated with P. aeruginosa (1) skin exposure in hot tubs and (2) lung exposure from inhaling aerosols.

Proton-pump inhibitors and the risk of antibiotic use and hospitalisation for pneumonia.

OBJECTIVE: To determine whether proton-pump inhibitor (PPI) use is associated with hospitalisations for pneumonia and with antibiotic use. DESIGN AND SETTING: Historical cohort study in the Australian veteran population, conducted from 1 January 2002 to 30 December 2006, comparing veterans exposed to PPIs with those not exposed. PARTICIPANTS: All 185,533 veterans who were Gold Card holders (ie, eligible for all health services subsidised by the Department of Veterans' Affairs) and aged 65 years and over at 1 January 2002 and had been prescribed at least one medicine in the previous 6 months. MAIN OUTCOME MEASURES: The primary endpoint was hospitalisation for pneumonia. Secondary endpoints included hospitalisation for bacterial pneumonia and dispensings of antibiotics commonly used to treat respiratory tract infections. RESULTS: After adjustment for potential confounders, we found an increased risk of hospitalisation for pneumonia among those exposed to PPIs compared with the unexposed group (rate ratio [RR], 1.16; 95% CI, 1.11-1.22). The risk was not increased for bacterial pneumonia (RR, 1.13; 95% CI, 0.98-1.31), which made up 8% of pneumonia cases. An increased risk of antibiotic dispensings was observed among those exposed to PPIs (RR, 1.23; 95% CI, 1.21-1.24). CONCLUSIONS: PPI dispensings were found to be associated with a small but significant increased risk of hospitalisation for pneumonia. While the increased risk is small, the prevalent use of PPIs means that many people could be affected.

Costs associated with shorter duration of antibiotic therapy in hospitalized patients with mild-to-moderate severe community-acquired pneumonia.

OBJECTIVES: The optimal duration of antibiotic therapy in patients with uncomplicated pneumonia may be shorter than that recommended in the current guidelines. A shorter duration will probably also lead to a cost reduction. This study evaluates the costs associated with 3 versus 8 day antibiotic therapy and subsequent follow-up in patients hospitalized with mild-to-moderate-severe community-acquired pneumonia. PATIENTS AND METHODS: The economic evaluation was based on primary resource utilization data collected within the framework of a randomized, double blind, placebo-controlled trial. As 3 day therapy was shown to be clinically not inferior to 8 day therapy, the cost-minimization analysis was performed based on direct medical and indirect non-medical costs, estimated from a societal perspective for the 28 days following hospital admission. RESULTS: Lower costs of shorter therapy during hospital admission (euro 209 lower) were partially offset by higher costs for primary healthcare providers (euro 66 higher). The average costs generated per patient by resource utilization during admission and follow-up were estimated as euro 3,959 in the 3 day group versus euro 4,102 in the 8 day group (difference euro 143 in favour of shorter therapy). The difference was affected by changes in assumptions concerning the unit costs for hospital stay but was consistently in favour of shorter therapy. CONCLUSIONS: Shorter duration of antibiotic therapy in hospitalized patients with uncomplicated pneumonia does not result in a substantial substitution of resource utilization to primary healthcare providers. As 3 day antibiotic therapy does not lead to inferior clinical results, these findings support a 3 day therapy as a more efficient strategy.

Nosocomial pneumonia: third-group chinolone versus clindamycin/ceftriaxone in modulation of the acute phase reaction and outcome and cost efficacy.

The effect of a third-group chinolone and clindamycin/ceftriaxone regarding outcome of patients with nosocomial pneumonia (NP) and modulation of the acute phase reaction as measured by immunologic parameters were studied in a prospective randomized trial on a surgical intensive care unit (ICU), as well as a comparison of therapy costs. Determination in 18 patients of serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, procalcitonin, and endotoxin levels and assessment of clinical outcome of NP were followed by the calculation of therapy costs. Decline in all immunologic parameters between the first and last measurement of each patient was slightly greater for clindamycin patients but statistically significant only for TNF-alpha. One-day therapy costs were 63.5 Euro (chinolone) versus 86.9 Euro (clindamycin/ceftriaxone). There was no difference in the outcome of NP treated with either a third-group chinolone or clindamycin/ceftriaxone.

Toward a zero VAP rate: personal and team approaches in the ICU.

In a fast-paced setting like the intensive care unit (ICU), nurses must have appropriate tools and resources in order to implement appropriate and timely interventions. Ventilator-associated pneumonia (VAP) is a costly and potentially fatal outcome for ICU patients that requires timely interventions. Even with established guidelines and care protocols, nurses do not always incorporate best practice interventions into their daily plan of care. Despite the plethora of information and guidelines about how to apply interventions in order to save lives, managers of ICUs are challenged to involve the bedside nurse and other ICU team members to apply these bundles of interventions in a proactive, rather than reactive, manner in order to prevent complications of care. The purpose of this article is to illustrate the success of 2 different methods utilized to improve patient care in the ICU. The first method is a personal process improvement model, and the second method is a team approach model. Both methods were utilized in order to implement interventions in a timely and complete manner to prevent VAP and its related problem, hospital-associated pneumonia, in the ICU setting. Success with these 2 methods has spurred an interest in other patient care initiatives.

Cost-effectiveness analysis of the treatment of ventilator-associated pneumonia with linezolid or vancomycin in Spain.

UNLABELLED: The aim of this study was to assess the cost-effectiveness of linezolid (LIN) versus vancomycin (VAN) for the treatment of ventilator-associated pneumonia (VAP) using a decision model analysis from the National Health System perspective. Patients and participants comprising four subgroups were analyzed: all, Gram-positive (GP), Staphylococcus aureus (SA), methicillin-resistant SA (MRSA). The treatments were LIN 600 mg i.v., every 12 hours, 10 days and VAN 1,000 mg i.v., every 12 hours 10 days. The primary outcome was the incremental cost-effectiveness of LIN in terms of cost per added quality-adjusted life year (QALY) gained. The secondary outcome was the marginal cost per year of life saved (LYS) generated by using LIN. Clinical cure and survival rates estimates were derived from a retrospective analysis of two trials comparing LIN with VAN. QALY was based on time-trade off study. Resource use and unit costs (Euros 2003) were obtained from Spanish VAP treatment and health cost databases. The additional QALY and LYS per LIN patients were 0.392; 0.688; 0.606; 1.805 and 0.471; 0.829; 0.729; 2.175 respectively, compared with those of VAN in the patients with VAP (all, GP, SA, and MRSA, respectively). The additional costs for LYS with LIN, as compared to VAN were 1,501.31; 827.63; 955.13 and 289.51 Euros, respectively. The additional cost per QALY with LIN was 1,803.87; 997.25; 1,149.00 and 348.85 Euros, respectively. CONCLUSIONS: LIN was more cost-effective than VAN in the treatment of VAP in Spain, with an additional cost per QALY/LYS gained below the acceptable threshold in Spain of Euros 30,000 for new therapies.

The gastrointestinal tract and ventilator-associated pneumonia.

The gastrointestinal tract is believed to play an important role in ventilator-associated pneumonia (VAP), because during critical illness the stomach often is colonized with enteric Gram-negative bacteria. These are the same bacteria that frequently are isolated from the sputum of patients with VAP. Interventions such as selective decontamination of the digestive tract (SDD), use of sucralfate for stress ulcer prophylaxis, and enteral feeding strategies that preserve gastric pH, or lessen the likelihood of pulmonary aspiration, are used to decrease the incidence of VAP. A review of both meta-analyses and large randomized controlled trials providing Level I evidence on these topics has led to the following conclusions. First, SDD substantially decreases the incidence of VAP and may have a modest positive effect on mortality. However, there is strong contravening evidence that SDD promotes infections by Gram-positive bacteria. In the context of an emerging public health crisis from the steady rise in drug-resistant Gram-positive bacteria, we cannot endorse the general use of SDD to prevent VAP. Rather, therapy should be focused on strategies other than antibiotic prophylaxis. Second, in patients who are at risk for clinically important gastrointestinal bleeding, a histamine-2 receptor antagonist should be used for stress ulcer prophylaxis, rather than sucralfate, because histamine-2 receptor antagonist provides substantially better protection without substantially increasing the risk of VAP. Third, post-pyloric enteral feeding may reduce the incidence of VAP.

Cost-effectiveness issues in ventilator-associated pneumonia.

Ventilator-associated pneumonia has attracted considerable interest as a subject of clinical efficacy assessment research. This article summarizes recommendations made by the United States Public Health Service Panel on Cost-Effectiveness in Health and Medicine and by a panel convened by the American Thoracic Society to address economic analyses in critical care. The following recommendations are made for the performance of cost-efficacy studies in ventilator-associated pneumonia. For mortality-based studies, only data from prospective and blinded randomized trials are suitable for analysis. For cost-minimization studies, observational studies may be useful but should use rigorous matching schemes. Estimates for the quality of life of patients surviving an episode of ventilator-associated pneumonia should be based on the disease that required mechanical ventilation or compared to data available for survivors of the respiratory distress syndrome, whichever diagnosis provides a lessened quality of life. Within an individual intensive care unit the greatest cost savings come from constructing a cohesive and unified approach to many issues seen in the unit.

Is bilateral protected specimen brush sampling necessary for the accurate diagnosis of ventilator-associated pneumonia?

BACKGROUND: Clinical acumen alone is unreliable in establishing a diagnosis of ventilator-associated pneumonia (VAP) and controversy exists over which diagnostic tools should be utilized to confirm a clinical suspicion of VAP. The purpose of this study was to determine the reliability of blind protected specimen brush (PSB) sampling in the diagnosis of VAP and if bilateral PSB sampling is necessary. METHODS: Prospective study comparing blind PSB sampling with bronchoscopic directed PSB sampling in thirty-four consecutive SICU patients with a clinical suspicion of VAP. All patients underwent blind PSB sampling followed by bronchoscopic directed contralateral PSB sampling. RESULTS: Twenty-four of 34 patients (71%) were diagnosed to have VAP. The concordance rate between blind and directed PSB samples was 53% (18/34). When blind PSB was positive (15/34), the contralateral sample yielded a different microorganism in three patients (9%). When blind PSB was negative (19/34), infection was present in the contralateral lung in nine patients (26%). Blind PSB sampling alone was inaccurate in 35% of patients. CONCLUSIONS: The low concordance between blind and directed PSB suggests the need to sample both lung fields. Bilateral PSB sampling can identify unsuspected pathogenic microorganisms in the contralateral lung.

Ventilator-associated pneumonia.

Ventilator-associated pneumonia is the most common nosocomial infection. Mortality rates, morbidity, and costs are all increased in the patient with VAP, and every measure should thus be taken to prevent its development. There are several clearly defined risk factors for VAP, and awareness of these can facilitate early diagnosis and hence treatment. In this article, we discuss the risk factors, strategies for prevention, approaches to diagnosis and management plan for the patient with VAP.