Higher clinical success in patients with ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus treated with linezolid compared with vancomycin: results from the IMPACT-HAP study.

INTRODUCTION: Controversy exists regarding optimal treatment for ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA). The primary objective of this study was to compare clinical success of linezolid versus vancomycin for the treatment of patients with MRSA VAP. METHODS: This was a multicenter, retrospective, observational study of patients with VAP (defined according to Centers for Disease Control and Prevention criteria) due to MRSA who were treated with linezolid or vancomycin. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. Clinical success was evaluated by assessing improvement or resolution of signs and symptoms of VAP by day 14. After matching on confounding factors, logistic regression models were used to determine if an association existed between treatment arm and clinical success. RESULTS: A total of 188 patients were evaluated (101 treated with linezolid and 87 with vancomycin). The mean ± standard deviation Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21 ± 11 for linezolid- and 19 ± 9 for vancomycin-treated patients (P = 0.041). Clinical success occurred in 85% of linezolid-treated patients compared with 69% of vancomycin-treated patients (P = 0.009). After adjusting for confounding factors, linezolid-treated patients were 24% more likely to experience clinical success than vancomycin-treated patients (P = 0.018). CONCLUSIONS: This study adds to the evidence indicating that patients with MRSA VAP who are treated with linezolid are more likely to respond favorably compared with patients treated with vancomycin.

Clinical experience in 52 patients with tigecycline-containing regimens for salvage treatment of Mycobacterium abscessus and Mycobacterium chelonae infections.

OBJECTIVES: We report the largest clinical experience using tigecycline-containing regimens for salvage treatment of patients with Mycobacterium abscessus and Mycobacterium chelonae. PATIENTS AND METHODS: Data were collected from 52 patients on emergency/compassionate use (n = 38) or two open-label studies (n = 7 patients each). Based on information that was available, 46 (88.5%) of the subjects received antibiotic therapy prior to treatment with tigecycline. Treatment groups were evaluated based on length of tigecycline therapy (<1 and ≥1 month). ClinicalTrials.gov identifiers: Study 205, NCT00600600 and Study 310, NCT00205816. RESULTS: The most commonly used concomitant antimicrobials were macrolides, amikacin and linezolid. Pulmonary disease was the most common presentation (36/52; 69.2%), and 58.3% of these patients had underlying cystic fibrosis. The majority were M. abscessus complex (n = 30) or M. chelonae/abscessus (n = 4). With therapy ≥1 month (mean, 255.0 ±â€Š265.7 days), 10/15 patients (66.7%) with cystic fibrosis and 16/26 (61.5%) overall were considered improved. Skin/soft-tissue/bone infections were the most common extrapulmonary infections. With therapy ≥1 month (mean, 143 ±â€Š123 days), 9/12 patients (75.0%) were considered improved. Nine of the 16 cases reported as failures regardless of site of infection occurred in patients who stopped treatment due to adverse events. There were eight deaths; none was related to tigecycline. CONCLUSIONS: Tigecycline given for ≥1 month as part of a multidrug regimen resulted in improvement in >60% of patients with M. abscessus and M. chelonae infections, including those with underlying cystic fibrosis, despite failure of prior antibiotic therapy. Adverse events were reported in >90% of cases, the most common being nausea and vomiting.

A comparison of microbiology and demographics among patients with healthcare-associated, hospital-acquired, and ventilator-associated pneumonia: a retrospective analysis of 1184 patients from a large, international study.

BACKGROUND: Acceptance of healthcare-associated pneumonia (HCAP) as an entity and the associated risk of infection by potentially multidrug-resistant (MDR) organisms such as methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas and Acinetobacter have been debated. We therefore compared patients with HCAP, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) enrolled in a trial comparing linezolid with vancomycin for treatment of pneumonia. METHODS: The analysis included all patients who received study drug. HCAP was defined as pneumonia occurring < 48 hours into hospitalization and acquired in a long-term care, subacute, or intermediate health care facility; following recent hospitalization; or after chronic dialysis. RESULTS: Data from 1184 patients (HCAP = 199, HAP = 379, VAP = 606) were analyzed. Compared with HAP and VAP patients, those with HCAP were older, had slightly higher severity scores, and were more likely to have comorbidities. Pseudomonas aeruginosa was the most common gram-negative organism isolated in all pneumonia classes [HCAP, 22/199 (11.1%); HAP, 28/379 (7.4%); VAP, 57/606 (9.4%); p = 0.311]. Acinetobacter spp. were also found with similar frequencies across pneumonia groups. To address potential enrollment bias toward patients with MRSA pneumonia, we grouped patients by presence or absence of MRSA and found little difference in frequencies of Pseudomonas and Acinetobacter. CONCLUSIONS: In this population of pneumonia patients, the frequencies of MDR gram-negative pathogens were similar among patients with HCAP, HAP, or VAP. Our data support inclusion of HCAP within nosocomial pneumonia guidelines and the recommendation that empiric antibiotic regimens for HCAP should be similar to those for HAP and VAP.

Absence of gender-based differences in outcome of patients with hospital-acquired pneumonia.

BACKGROUND: The objective of this analysis was to evaluate the association between gender and clinical outcomes in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) since data thus far are controversial. METHODS: Data from a convenience sample of ICU patients with HAP, including ventilator-associated and health care-associated pneumonia, were retrospectively collected from four academic institutions (Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia [IMPACT-HAP] study). Outcomes included 28-day mortality, clinical failure at day 14, hospital and ICU length of stay (LOS), and duration of mechanical ventilation. We compared baseline characteristics and performed multivariate analysis to identify factors independently associated with mortality. RESULTS: Among 416 patients, 271 were men and 145 were women. Women were older (62.4±16.9 vs. 55.7±16.5 years, p<0.001) and more critically ill, with Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 21 vs. 19 (p=0.004). Day-28 mortality was 30% for women and 24% for men (p=0.25). Increased 28-day mortality was associated with severity of illness, age, ventilator-associated pneumonia, vascular disease, and hospital LOS prior to pneumonia diagnosis. No significant differences were found in the distribution of bacteria pathogens or in clinical failure rates (36% vs. 31%) between genders. Duration in days of mechanical ventilation, ICU LOS and hospital LOS after the diagnosis of pneumonia were not significantly different between men and women. Analyzing data for women based on presumed pre- or postmenopausal status (age breakpoint of 50 years), showed an increased in ICU LOS (15 vs. 25 days; p=0.0026) and hospital LOS (22 vs. 30 days; p=0.05) for women ≤50 years. No differences were noted in 28-day mortality (24.3% vs. 13.1%; p=0.18) in women ≤50 years of age. CONCLUSIONS: In ICU patients with pneumonia, female gender was not associated with worse outcomes or increased resource utilization compared to male gender. Further studies are needed to evaluate menopausal status and outcomes in women with pneumonia.

Emergence of methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of late-onset nosocomial pneumonia in intensive care patients in the USA.

OBJECTIVE: To compare demographic and clinical characteristics, and methicillin-resistant Staphylococcus aureus (MRSA) strain characteristics, in patients with early-onset (EO) and late-onset (LO) MRSA nosocomial pneumonia. METHODS: This was a retrospective analysis of data from a multicenter observational study of nosocomial pneumonia patients admitted between November 2008 and July 2010. Laboratory analyses performed on MRSA isolates included confirmation of antimicrobial susceptibility and heteroresistance to vancomycin, USA typing, staphylococcal cassette chromosome (SCC) mec typing, and detection of Panton-Valentine leukocidin (PVL) genes. RESULTS: We identified 134 patients; 42 (31%) had EO MRSA pneumonia and 92 (69%) had LO MRSA pneumonia. The patients in the LO group were more likely to have risk factors for multidrug-resistant pathogens (98% vs. 76%, p<0.001). The MRSA USA300 strain was found with equal frequency in the EO and LO groups. Likewise, both groups had similar frequencies of isolates exhibiting PVL and SCCmec type IV. CONCLUSIONS: Our findings provide further evidence of the continued migration of community-associated MRSA into the healthcare setting in the USA. MRSA USA300 genotype has emerged as a significant cause of LO nosocomial pneumonia in intensive care units. Appropriate anti-MRSA antimicrobial therapy should be considered for both EO and LO hospital-acquired pneumonia and ventilator-associated pneumonia.

Analysis of pathogen and host factors related to clinical outcomes in patients with hospital-acquired pneumonia due to methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial pneumonia. To characterize pathogen-derived and host-related factors in intensive care unit (ICU) patients with MRSA pneumonia, we evaluated the Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) database. We performed multivariate regression analyses of 28-day mortality and clinical response using univariate analysis variables at a P level of <0.25. In isolates from 251 patients, the most common molecular characteristics were USA100 (55.0%) and USA300 (23.9%), SCCmec types II (64.1%) and IV (33.1%), and agr I (36.7%) and II (61.8%). Panton-Valentine leukocidin (PVL) was present in 21.9%, and vancomycin heteroresistance was present in 15.9%. Mortality occurred in 37.1% of patients; factors in the univariate analysis were age, APACHE II score, AIDS, cardiac disease, vascular disease, diabetes, SCCmec type II, PVL negativity, and higher vancomycin MIC (all P values were <0.05). In multivariate analysis, independent predictors were APACHE II score (odds ratio [OR], 1.090; 95% confidence interval [CI], 1.041 to 1.141; P < 0.001) and age (OR, 1.024; 95% CI, 1.003 to 1.046; P = 0.02). Clinical failure occurred in 36.8% of 201 evaluable patients; the only independent predictor was APACHE II score (OR, 1.082; 95% CI, 1.031 to 1.136; P = 0.002). In summary, APACHE II score (mortality, clinical failure) and age (mortality) were the only independent predictors, which is consistent with severity of illness in ICU patients with MRSA pneumonia. Interestingly, our univariate findings suggest that both pathogen and host factors influence outcomes. As the epidemiology of MRSA pneumonia continues to evolve, both pathogen- and host-related factors should be considered when describing epidemiological trends and outcomes of therapeutic interventions.

Incidence of nephrotoxicity and association with vancomycin use in intensive care unit patients with pneumonia: retrospective analysis of the IMPACT-HAP Database.

BACKGROUND: The 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care-associated (HCAP) pneumonia. OBJECTIVE: The goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP. METHODS: This was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50% above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction. RESULTS: Of the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63% were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4%) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95% CI, 1.9-13.9]; P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95% CI, 1.09-6.54]; P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95% CI, 1.02-1.23]; P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7% at a trough <10 mg/L to 34% at >20 mg/L (P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels <15 mg/L to 7.4 days at >20 mg/L (Kaplan-Meier analysis, P = 0.0003). CONCLUSIONS: Nephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.

Severity of disease and clinical outcomes in patients with hospital-acquired pneumonia due to methicillin-resistant Staphylococcus aureus strains not influenced by the presence of the Panton-Valentine leukocidin gene.

BACKGROUND: Patients with community-acquired pneumonia (CAP) infected with methicillin-resistant Staphylococcus aureus (MRSA) strains carrying the Panton-Valentine leukocidin (PVL) gene have severe clinical presentation and poor clinical outcomes. Antibiotics that suppress toxin production have been suggested for the management of these patients. The objective of this study was to compare the severity of disease and clinical outcomes of patients with hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) infected with MRSA carrying the PVL gene with those patients infected with MRSA strains that do not carry the PVL gene. METHODS: This was a multicenter observational study of patients with HAP and VAP. MRSA isolates were subjected to genetic analysis to define the presence of the PVL gene, the USA type and the staphylococcal cassette chromosome mec type. Severity of disease was evaluated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The primary clinical outcome was mortality at hospital discharge. RESULTS: A total of 109 cases of MRSA HAP/VAP were evaluated. The incidence of PVL(+) MRSA was 27%. APACHE II score at diagnosis of HAP/VAP was 21 ± 8 for PVL(+) MRSA and 20 ± 6 for PVL(-) MRSA (P = .67). Mortality was 10% (3/29) for patients with PVL(+) MRSA versus 10% (8/80) for patients with PVL(-) MRSA (P > .99). CONCLUSIONS: In patients with HAP or VAP due to MRSA, severity of disease and clinical outcomes are not influenced by the presence of the PVL gene. Therapeutic strategies directed to block PVL exotoxin may not impact outcomes in these patients.

Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study.

BACKGROUND: The American Thoracic Society and Infectious Diseases Society of America provide guidelines for management of hospital-acquired, ventilator-associated, and health-care-associated pneumonias, consisting of empirical antibiotic regimens for patients at risk for multidrug-resistant pathogens. We aimed to improve compliance with these guidelines and assess outcomes. METHODS: We implemented a performance-improvement initiative in four academic medical centres in the USA with protocol-based education and prospective observation of outcomes. Patients were assessed for severity of illness and followed up until death, hospital discharge, or day 28. We included patients in intensive-care units who were at risk for multidrug-resistant pneumonia and were treated empirically. FINDINGS: 303 patients at risk for multidrug-resistant pneumonia were treated empirically, and prescribed treatment was guideline compliant in 129 patients and non-compliant in 174 patients. 44 (34%) patients died before 28 days in the compliance group and 35 (20%) died in the non-compliance group. Five patients in the compliance group and seven in the non-compliance group were lost to follow-up after day 14. Kaplan-Meier estimated survival to 28 days was 65% in the compliance group and 79% in the non-compliance group (p=0·0042). This difference persisted after adjustment for severity of illness. Median length of stay and duration of mechanical ventilation did not differ between groups. Compliance failures included non-use of dual treatment for Gram-negative pathogens in 154 patients and absence of meticillin-resistant Staphylococcus aureus coverage in 24 patients. For patients in whom pathogens were subsequently identified, empirical treatment was active in 79 (81%) of 97 of patients receiving compliant therapy compared with 109 (85%) of 128 of patients receiving non-compliant therapy. INTERPRETATION: Because adherence with empirical treatment was associated with increased mortality, we recommend a randomised trial be done before further implementation of these guidelines. FUNDING: Pfizer, US Medical.

Development and implementation of a performance improvement project in adult intensive care units: overview of the Improving Medicine Through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) study.

INTRODUCTION: In 2005 the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) published guidelines for managing hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and healthcare-associated pneumonia (HCAP). Although recommendations were evidence based, collective guidelines had not been validated in clinical practice and did not provide specific tools for local implementation. We initiated a performance improvement project designated Improving Medicine Through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) at four academic centers in the United States. Our objectives were to develop and implement the project, and to assess compliance with quality indicators in adults admitted to intensive care units (ICUs) with HAP, VAP, or HCAP. METHODS: The project was conducted in three phases over 18 consecutive months beginning 1 February 2006: 1) a three-month planning period for literature review to create the consensus pathway for managing nosocomial pneumonia in these ICUs, a data collection form, quality performance indicators, and internet-based repository; 2) a six-month implementation period for customizing ATS/IDSA guidelines into center-specific guidelines via educational forums; and 3) a nine-month post-implementation period for continuing education and data collection. Data from the first two phases were combined (pre-implementation period) and compared with data from the post-implementation period. RESULTS: We developed a consensus pathway based on ATS/IDSA guidelines and customized it at the local level to accommodate formulary and microbiologic considerations. We implemented multimodal educational activities to teach ICU staff about the guidelines and continued education throughout post-implementation. We registered 432 patients (pre- vs post-implementation, 274 vs 158). Diagnostic criteria for nosocomial pneumonia were more likely to be met during post-implementation (247/257 (96.1%) vs 150/151 (99.3%); P = 0.06). Similarly, empiric antibiotics were more likely to be compliant with ATS/IDSA guidelines during post-implementation (79/257 (30.7%) vs 66/151 (43.7%); P = 0.01), an effect that was sustained over quarterly intervals (P = 0.0008). Between-period differences in compliance with obtaining cultures and use of de-escalation were not statistically significant. CONCLUSIONS: Developing a multi-center performance improvement project to operationalize ATS/IDSA guidelines for HAP, VAP, and HCAP is feasible with local consensus pathway directives for implementation and with quality indicators for monitoring compliance with guidelines.

Infecciones causadas por streptococcus pneumoniae en pacientes con enfermedad por el virus de inmunodeficiencia humana / Streptococcus pneumoniae infections in human immunodeficiency virus symptomatic patients

Se presenta información acerca de las características de la infección por S. pneumoniae en pacientes infectados por VIH. Se discuten la patogénesis y consecuencias clínicas de la infección neumocóccica en pacientes infectados por VIH, presentando ejemplos de nuestra casuística en la Universidad de Miami. Finalmente, se discute la prevención de esta infección con énfasis en el uso de la vacuna anti neumocóccica

Poliradiculomielopatia causada por citomegalovirus en pacientes con SIDA / Cytomegalovirus polyradiculomyelopathy in AIDS

Se presenta una serie de 7 pacientes con SIDA en quienes se diagnosticó poliradiculomielopatía causada por Citomegalovirus (CMV-PRAM), con el objetivo de evaluar la eficacia del tratamiento con ganciclovir, foscarnet, o la combinación de ambos agentes. Se realizaron evaluaciones clínicas y neurológicas al momento de presentación y durante el tratamiento para el CMV. La fuerza muscular fue establecida de acuerdo a la escala del Medical Research Council (MRC). Se clasificó la respuesta al tratamiento de acuerdo al grado de mejoría en la fuerza muscular. En 6 de los 7 pacientes se observó una mejoría en la fuerza muscular con tratamiento anti-CMV alcanzando grado 4, o una mejoría de por lo menos 3 grados de acuerdo a la escala MRC. El paciente restante tuvo una respuesta intermedia. CMV-PRAM puede ser tratada con ganciclovir o la combinación de ganciclovir y foscarnet con buenos resultados.

Poliradiculomielopatia causada por citomegalovirus en pacientes con SIDA / Cytomegalovirus polyradiculomyelopathy in AIDS

Se presenta una serie de 7 pacientes con SIDA en quienes se diagnosticó poliradiculomielopatía causada por Citomegalovirus (CMV-PRAM), con el objetivo de evaluar la eficacia del tratamiento con ganciclovir, foscarnet, o la combinación de ambos agentes. Se realizaron evaluaciones clínicas y neurológicas al momento de presentación y durante el tratamiento para el CMV. La fuerza muscular fue establecida de acuerdo a la escala del Medical Research Council (MRC). Se clasificó la respuesta al tratamiento de acuerdo al grado de mejoría en la fuerza muscular. En 6 de los 7 pacientes se observó una mejoría en la fuerza muscular con tratamiento anti-CMV alcanzando grado 4, o una mejoría de por lo menos 3 grados de acuerdo a la escala MRC. El paciente restante tuvo una respuesta intermedia. CMV-PRAM puede ser tratada con ganciclovir o la combinación de ganciclovir y foscarnet con buenos resultados. (AU)

Trombocitopenia asociada a infección con virus de inmunodeficiencia humana tipo 1 (HIV-1): tratamiento con danazol / Danazol therapy in thrombocytopenia associated with HIV-1 infection

Objetivo: Evaluar la eficacia del danazol para el tratamiento de la trombocitopenia asociada con el virus de la inmunodeficiencia humana tipo 1 (HIV-1). Pacientes y Métodos: Estudio retrospectivo, diseño serie de casos. Se identificaron 8 pacientes con trombocitopenia asociada a infección con HIV-1 que fueron tratados con danazol (300-800 mg/día) por más de 3 meses. El seguimiento fue de 3 meses a 2 años. Se definió respuesta favorable al tratamiento como un incremento en el recuento de plaquetas por encima del 25 por ciento con referencia a los valores pre-tratamiento. Resultados: El recuento de plaquetas promedio(ñ desviación estándar) antes de la terapia con danazol fue de 51ñ24 x 10/L, con un rango de 19-88 x 10/L.Siete (87 por ciento) de los 8 pacientes tuvieron respuestas favorables al danazol. Los recuentos promedio a 12 y 24 meses de terapia fueron 104+108 x 10/L, y 112ñ28 x 10/L, respectivamente. Se observó una tendencia al incremento de los recuentos plaquetarios durante el tratamiento con danazol. Conclusión: Danazol puede ser de utilidad en el tratamiento de la trombocitopenia asociada a HIV-1.

Avances recientes en HIV-SIDA: patogénesis, historia natural y carga viral / Recent developments in HIV/SIDA: pathogenesis, natural history and viral load

Results of recent research investigations have given us a new understanding of the pathogenesis of HIV infection. This findings provide us with a kinetic model of pathogenesis in which continuous, high grade viral replication is the principal force driving the destruction of CD4 lymphocytes. This knowledge will lead us to design better treatment strategies directed to curtail viral replication and prevent the emergence of viral resistance, and the use of combination antiretroviral therapy is a first example of these new strategies. The concept of viral load is introduced, and we discuss the usefulness of viral load in the clinical prognosis of this disease, and its use as an aid in the decision making process when starting or modifying antiretroviral therapy in our patients.