Cause Of Ventilator-associated Pneumonia Research Articles

Inhaled aminoglycosides in cancer patients with ventilator-associated Gram-negative bacterial pneumonia: safety and feasibility in the era of escalating drug resistance

We sought to evaluate the safety and feasibility of inhaled aminoglycosides or colistin in cancer patients with ventilator-associated pneumonia (VAP) due to Gram-negative bacteria (GNB). A retrospective case-matched study was obtained after obtaining IRB approval in patients at the intensive care unit at our NCI-designated comprehensive cancer center between 1999 and 2005. Sixteen patients with GNB-VAP who received inhaled aminoglycosides or colistin were compared with 16 patients who had received these antibiotics intravenously alone. Eligible patients were required to have received at least six doses of inhaled therapy, or 3 or more days of intravenous therapy. Clinical Pulmonary Infection Scores were used to assess pneumonia severity. Standard ATS criteria were used to define VAP. Patients treated with inhaled antibiotics were less likely to have received corticosteroids (13% vs 50%; P < 0.02) and had a higher median baseline creatinine level (0.85 vs 0.6 mg/dL; P < 0.02) than patients treated intravenously. Pseudomonas aeruginosa (69%) was the most common cause of VAP. There were no serious adverse events associated with inhaled antibiotics. Patients who received these antibiotics intravenously developed renal dysfunction (31%); none of the patients treated with inhaled antibiotics developed nephrotoxicity (P < or = 0.04). Patients treated with inhaled antibiotics were more likely to have complete resolution of clinical (81% vs 31% in the intravenous antibiotic group; P < 0.01) and microbiologic infection (77% vs 8% in the intravenous antibiotic group: P < 0.0006). In a multivariate analysis adjusted for corticosteroid use, inhaled antibiotic therapy was predictive of complete clinical resolution (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.1, 37.6; P < 0.04) and eradication of causative organisms (OR 36.7; 95% CI, 3.3, 412.2; P < 0.003). In critically ill cancer patients with Gram-negative VAP, inhaled aminoglycosides were tolerated without serious toxicity and may lead to improved outcome.

Risk factors and pathogenic analysis in the newborn infants with ventilator-associated pneumonia

Objective To investigate the risk factors and microbial causes related to the pathogenesis of ventilator-associated pneumonia(VAP).Methods Totaly 138 intubated newborn infants for longer than 48 hours in Ningbo Women and Children's Hospital were studied,who were divided into VAP group (56 cases)and non VAP group(82 cases).Microbial causes of VAP were analyzed.Results Malnutrition,repeated tracheal intubation,repeated endotracheal suctioning,indwelling tube,posture,hyaline membrane disease,gestational age,birth weight,duration of intubation,duration of hospitalization were independent risk factors for ventilator-associated pneumonia(P<0.05).Klebsiella pneumoniae,pseudomonas aeruginosa,acinetobacter species and enterobacter cloacae were the main pathogenic bacteria of VAP.Conclusion Shortening of mechanical ventilation duration,avoiding repeated tracheal intubation and indwelling tube usage,semi-fowler positioning can lower the incidence of VAP.Pathogenic bacteria control is essential for VAP. Key words: Newborn; Ventilator-associated pneumonia; Risk factors

Predicting pathogens causing ventilator-associated pneumonia using a Bayesian network model

We previously validated a Bayesian network (BN) model for diagnosing ventilator-associated pneumonia (VAP). Here, we report on the performance of the model to predict microbial causes of VAP and to select antibiotics. Pathogens were grouped into seven categories based upon the antibiotic susceptibility and epidemiological characteristics. Colonization of the upper respiratory tract was modelled in the BN and depended--in additional steps--on (i) duration of admission and ventilation, (ii) previous culture results and (iii) previous antibiotic use. A database with 153 VAP episodes and their microbial causes was used as reference standard. Appropriateness of antibiotic prescription, with fixed choices for pathogens predicted, was determined. One hundred and seven VAP episodes were monobacterial and 46 were caused by two pathogens. Using duration of admission and ventilation only, areas under the receiver operating curve (AUC) ranged from 0.511 to 0.772 for different pathogen groups, and model predictions significantly improved when adding information on culture results, but not when adding information on antibiotic use. The best performing model (with all information) had AUC values ranging from 0.859 for Acinetobacter spp. to 0.929 for Streptococcus pneumoniae. With this model, 91 (85%) and 29 (63%) of all pathogen groups were correctly predicted for monobacterial and polymicrobial VAP, respectively. With fixed antibiotic choices linked to pathogen groups, 92% of all episodes would have been treated appropriately. The BN models' performance to predict pathogens causing VAP improved markedly with information on colonization, resulting in excellent pathogen prediction and antibiotic selection. Prospective external validation is needed.

Ventilator-associated pneumonia and new airway technologies

Current endotracheal and tracheostomy tubes have high volume low pressure cuffs. These cuffs are ineffective at preventing the ongoing pulmonary aspiration of oropharyngeal and gastric contents. This ubiquitous complication of intubation is the most important cause of ventilator-associated pneumonia (VAP), the commonest and most devastating nosocomial infection in the Intensive Care Unit (ICU). Current tracheal tubes are made of relatively fixed curved PVC, and this produces forces on the airway tissues which is associated with laryngeal and tracheal injury. There is a need for the development of tracheal tube technologies to prevent aspiration injury and the reduce airway injury associated with mechanical ventilation of the critically ill. Given the costs associated with VAP there is currently a massive mismatch in what we spend on prevention.

Effect of subglottic secretion drainage on the prevention of ventilator associated pneumonia

Objective To assess the influence of subglottic secretion drainage(SSD)on the prevention of ventilator associated pneumonia(VAP).Methods 63 patients in the intensive care unit(ICU)who received mechanical ventilation above 48 hours were divided into two groups named group A(31 cases)and group B(32 cases).Group A received SSD 1 time per 6 hours while group B only got SSD at 48 hours,the 4th,7th and 14th days when samples were got.We brushed away secretion from airway and also monitored bacteriology of the subglottic secretion between the two groups. Results The incidence rate of VAP in group A was 6.1%and was evidently lower than that of group B(P 0.05).The onset time of VAP was later anti the bacteria number in the subglottic secretion was less in group A than those in group B(P<0.01).The same bacteria strain was found in the subglottic secretion and airway secretions in 13 patients out of 22 VAP patients.The dominant bacteria were P.aeruginosa,K.pneumonia,Staphylococcus aureus and Pseudomonas stenotrophomonas. Conclusion SSD could reduce the bacteria concentration in subglottic secretion,decrease VAP incidence and delay the onset of VAP.Migration of dominant bacteria from the subglottic secretion was one of the important causes of VAP. Key words: Ventilator associated pneumonia; Subglottic secretion drainage; Intensive care unit

Malassezia furfur im Trachealsekret beatmeter Frühgeborener

Ventilated neonates are prone to acquire ventilator-associated pneumonia (VAP). Consequently early diagnosis of pneumonia is required. Beside bacteria, fungi are suspected as a cause of VAP. However, fungal colonisation and infection of the lung have not been studied systematically. The purpose of this study was to evaluate pulmonary fungal colonisation in ventilated neonates and premature infants. 187 tracheal aspirates (TA) from 29 ventilated neonates (23-35 weeks gestational age) were investigated. TAs were evaluated microscopically and by culture. Data were matched with clinical signs of VAP or sepsis. Candida species were not detected in TA or culture. In contrast, Malassezia furfur (Mf), a lipophilic fungus, was detected from the 10th, 21st and 31st postnatal days onwards in TAs of 3 out of 17 extremely prematures (gestational age at birth < 25 weeks). The presence of Mf was associated with clinical deterioration either immediately or a few days after the first positive Mf smear. Topic steroids were more frequently applied to Mf-positive ELBW infants (p = 0.03). In vitro, natural surfactant was demonstrated to be a sufficient substrate for Mf in culture. This is the first report on Mf lung colonisation of ELBWI during mechanical ventilation. Because Mf is generally not detected in standard cultures it appears to be an overlooked, potentially pathogenic fungus in prematures. Mf must be considered in the differential diagnosis of VAP in ELBWI exposed to topical steroids, especially when natural surfactant was administered.

A Bad Bug Takes on a New Role as a Cause of Ventilator-associated Pneumonia

Despite use of preventive strategies and significant advances in supportive care and antimicrobial therapy, ventilator-associated pneumonia (VAP) remains an important cause of morbidity and mortality (1). Although bacteria cause most VAPs, invasive pulmonary aspergillosis (IPA) is extremely uncommon, except when classical risk factors for aspergillosis (hematologic cancer, neutropenia, transplantation) are present. In this issue of the Journal (pp. 27‐34), Meersseman and colleagues (2) report their findings using detection of Aspergillus galactomannan (GM) (cell wall constituent released during tissue invasion) in bronchoalveolar lavage (BAL) fluid (BAL-GM) for diagnosing VAP caused by Aspergillus spp. Upon diagnosis of pneumonia, 110 adults at risk for IPA underwent BAL for culture and GM detection, serum GM, and chest computed tomography (CT). Only 22% of patients were neutropenic and 67% had underlying diseases other than hematologic cancer, including cirrhosis and chronic obstructive pulmonary disease (COPD). Twenty-six patients (24%) developed histopathologically proven IPA. The diagnostic sensitivity and specificity of BAL-GM was 88 and 87%, respectively, compared with 42% sensitivity for serum GM. Serum GM and BAL culture remained negative in 11 patients (42%) in whom BAL-GM was positive. Chest CT was of limited diagnostic value. The findings of this prospective study, backed by an impressive 95% autopsy rate, underscore the increasingly important role that Aspergillus species play as a cause of VAP in apparently immunocompetent intensive care unit (ICU) patients

Etiología de la neumonía asociada a ventilación mecánica en un hospital clínico: Asociación con co-morbilidad, uso previo de antimicrobianos y mortalidad

Ventilator-associated pneumonia (VAP) is a complication with an increased risk of morbidity and mortality. Inadequate antibiotic treatment is a risk factor of mortality which can be improved. For this reason it is important to know the local etiology of VAP. During a one year-period we investigated the etiology of VAP in a teaching hospital. Forty eight VAP were included, of which 19 were women. The median age was 59.5 (range 17-91 years), twelve VAP were early onset. Methicillin resistant Staphylococcus aureus (MRSA) was the main microorganism isolated, regardless of timing of diagnosis of VAP, followed by polimicrobial etiology, Acinetobacter sp and P. aeruginosa. Etiology was not associated with comorbidity; however previous antibiotic use was related with MRSA and polymicrobial etiology. Mortality was 35% and was mainly associated with P. aeruginosa isolation. MRSA was the main cause of VAP regardless of the timing of its occurrence.

Ventilator-Associated Pneumonia: A Review

Ventilator-associated pneumonia is the most frequent intensive care unit (ICU)-related infection in patients requiring mechanical ventilation. In contrast to other ICU-related infections, which have a low mortality rate, the mortality rate for ventilator-associated pneumonia ranges from 20% to 50%. These clinically significant infections prolong duration of mechanical ventilation and ICU length of stay, underscoring the financial burden these infections impose on the health care system. The causes of ventilator-associated pneumonia are varied and differ across different patient populations and different types of ICUs. This varied presentation underscores the need for the intensivist treating the patient with ventilator-associated pneumonia to have a clear knowledge of the ambient microbiologic flora in their ICU. Prevention of this disease process is of paramount importance and requires a multifaceted approach. Once a diagnosis of ventilator-associated pneumonia is suspected, early broad-spectrum antibiotic administration decreases morbidity and mortality and should be based on knowledge of the sensitivities of common infecting organisms in the ICU. De-escalation of therapy, once final culture results are available, is necessary to minimize development of resistant pathogens. Duration of therapy should be based on the patient's clinical response, and every effort should be made to minimize duration of therapy, thus further minimizing the risk of resistance.

VAP Prevention with an Antiseptic Mouthwash

Aspiration of oropharyngeal secretions around an endotracheal tube is a leading cause of ventilator-associated pneumonia (VAP). Although several

Morbidity and cost burden of methicillin-resistant Staphylococcus aureus in early onset ventilator-associated pneumonia

IntroductionTo gain a better understanding of the clinical and economic outcomes associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in patients with early onset ventilator-associated pneumonia (VAP), we retrospectively analyzed a multihospital US database to identify patients with VAP over a 24 month period (2002–2003).MethodData recorded included physiologic, laboratory, culture, and other clinical variables from 59 institutions. VAP was defined as new positive respiratory culture after at least 24 hours of mechanical ventilation (MV) and the presence of primary or secondary ICD-9-CM diagnosis codes of pneumonia. Outcomes measures included in-hospital morbidity and mortality for the population overall and after onset of VAP (duration of MV, intensive care unit [ICU] stay, in-hospital stay, and case mix and severity-adjusted operating cost). The overall cost was calculated at the hospital level using the Center for Medicare and Medicaid Services Cost/Charge Index for each calendar year.ResultsA total of 499 patients were identified as having VAP. S. aureus was the leading organism (31% of isolates). Patients with MRSA were significantly older than patients with methicillin-sensitive Staphylococcus aureus (MSSA; median age 74 versus 67 years, P < 0.05) and more likely to be medical patients. Compared with MSSA patients, MRSA patients on average consumed excess resources of 4.4 (95% confidence interval 0.6–8.2) overall MV days, 3.8 (-0.5 to +8.0) days of inpatient length of stay (LOS), 5.3 (1.0–9.7) ICU days, and US$7731 (-US$8393 to +US$23,856) total cost after controlling for case mix and other factors. Furthermore, MRSA patients needed excess resources after the onset of VAP (4.5 [95% confidence interval 1.0–8.1] MV days, 3.7 [-0.5 to +8.0] inpatient days, and 4.4 [0.4–8.4] ICU days) after controlling for the same case mix and admission severity covariates.ConclusionS. aureus remains a common cause of VAP. VAP due to MRSA was associated with increased overall LOS, ICU LOS, and attributable ICU LOS compared with MSSA-related VAP. Although not statistically significant because of small sample size and large variation, the attributable excess costs of MRSA amounted to approximately US$8000 per case after controlling for case mix and severity.

Amoeba-Resisting Bacteria and Ventilator-Associated Pneumonia

To evaluate the role of amoeba-associated bacteria as agents of ventilator-associated pneumonia (VAP), we tested the water from an intensive care unit (ICU) every week for 6 months for such bacteria isolates; serum samples and bronchoalveolar lavage samples (BAL) were also obtained from 30 ICU patients. BAL samples were examined for amoeba-associated bacteria DNA by suicide-polymerase chain reaction, and serum samples were tested against ICU amoeba-associated bacteria. A total of 310 amoeba-associated bacteria from10 species were isolated. Twelve of 30 serum samples seroconverted to one amoeba-associated bacterium isolated in the ICU, mainly Legionella anisa and Bosea massiliensis, the most common isolates from water (p=0.021). Amoeba-associated bacteria DNA was detected in BAL samples from two patients whose samples later seroconverted. Seroconversion was significantly associated with VAP and systemic inflammatory response syndrome, especially in patients for whom no etiologic agent was found by usual microbiologic investigations. Amoeba-associated bacteria might be a cause of VAP in ICUs, especially when microbiologic investigations are negative.

Amoeba-resisting bacteria and ventilator-associated pneumonia.

Vibrio cholerae in O-group 139 was first isolated in 1992 and by 1993 had been found throughout the Indian subcontinent. This epidemic expansion probably resulted from a single source after a lateral gene transfer (LGT) event that changed the serotype of an epidemic V. cholerae O1 El Tor strain to O139. However, some studies found substantial genetic diversity, perhaps caused by multiple origins. To further explore the relatedness of O139 strains, we analyzed nine sequenced loci from 96 isolates from patients at the Infectious Diseases Hospital, Calcutta, from 1992 to 2000. We found 64 novel alleles distributed among 51 sequence types. LGT events produced three times the number of nucleotide changes compared to mutation. In contrast to the traditional concept of epidemic spread of a homogeneous clone, the establishment of variant alleles generated by LGT during the rapid expansion of a clonal bacterial population may be a paradigm in infections and epidemics.

The Significance of Distal Bronchial Samples with Commensals in Ventilator-Associated Pneumonia: Colonizer or Pathogen?

To investigate the role of oropharyngeal and cutaneous commensal microorganisms (OCCs) as a cause of ventilator-associated pneumonia (VAP). Retrospective analysis of the medical and microbiological records. One medical-surgical ICU. All VAP episodes recorded during a 10-year period were reviewed. All patients with suspected VAP underwent bronchoscopy with protected-specimen brush (PSB) sampling and BAL before any change in antibiotic therapy was made. OCC-VAP was defined as VAP with significant growth in quantitative cultures (PSB yielded > or = 10(3) cfu/mL and/or BAL yielded > or = 10(4) cfu/mL) of OCCs only. Three experts reviewed the episodes. Exposed patients (ie, those with OCC-VAP) and unexposed patients (ie, patients without VAP) matched on condition severity at ICU admission and mechanical ventilation duration were compared. Twenty-nine episodes in 28 patients with > or = 10(4) cfu/mL OCCs in BAL fluid and/or > or = 10(3) cfu/mL OCCs in PSB specimens were found. All patients in these episodes had new radiologic lung infiltrates, with 26 episodes involving purulent tracheal aspirates, 23 episodes involving temperatures > or = 38.5 degrees C, and 18 episodes involving > or = 11,000 leukocytes/ microL. The main OCCs found were non-beta-hemolytic Streptococcus spp (n = 12), Neisseria spp (n = 7), and coagulase-negative Staphylococcus spp (n = 6). Other possible reasons for fever and the presence of new chest infiltrates were found in 20 and 17 patients, respectively. Histologic evidence of pneumonia was found in 2 of the 10 patients who died. The three experts agreed on the diagnosis for 23 patients. In the OCC-VAP group only, the mean (+/- SD) logistic organ dysfunction (LOD) scores increased significantly (LOD score, 2 +/- 4; p = 0.008) during the 3 days before bronchoscopy, and ICU stay duration was longer than in the unexposed group. The exposed/unexposed study found no difference in mortality. OCCs may behave like classic nosocomial pathogens in critically ill patients.

Comparison of Ampicillin‐Sulbactam and Imipenem‐Cilastatin for the Treatment ofAcinetobacterVentilator‐Associated Pneumonia

Acinetobacter organisms, which are a common cause of ventilator-associated pneumonia (VAP) in some health care centers, are becoming more resistant to such first-line agents as imipenem-cilastatin (Imi-Cil). Sulbactam has good in vitro activity against Acinetobacter organisms; thus, ampicillin-sulbactam (Amp-Sulb) may be a viable treatment alternative. The outcomes for critically ill trauma patients with Acinetobacter VAP treated with either Amp-Sulb or Imi-Cil were compared retrospectively. A total of 77 episodes in 75 patients were studied. Fourteen patients were treated with Amp-Sulb, and 63 patients were treated with Imi-Cil. Treatment efficacy was similar in the Amp-Sulb and Imi-Cil groups (93% vs. 83%, respectively; P>.05). No statistically significant differences between groups were noted with regard to associated mortality, duration of mechanical ventilation, or length of stay in the intensive care unit or hospital. However, adjunctive aminoglycoside therapy was used more often in the Amp-Sulb group. Patients generally received Amp-Sulb because of imipenem resistance. Amp-Sulb was effective in treating a small number of patients with Acinetobacter VAP; however, more data are needed.

Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a frequent cause of ventilator-associated pneumonia. Recent evidence suggests that production of type III secretion proteins is correlated with increased pathogenicity in both cellular and animal models of infection. The objective of this study was to determine whether this system contributes to disease severity in humans with ventilator-associated pneumonia. Retrospective pilot cohort study. University hospital. Thirty-five mechanically ventilated patients with bronchoscopically confirmed ventilator-associated pneumonia caused by P. aeruginosa. Ventilator-associated pneumonia was categorized as severe (patients died or had a recurrence of their pneumonia despite appropriate antibiotic therapy) or mild (patients uneventfully recovered from their pneumonia). The type III secretion genotypes and phenotypes of isolates cultured from the patients with ventilator-associated pneumonia were determined. Whereas every examined isolate harbored type III secretion genes, only 27 (77%) were capable of secreting detectable amounts of type III proteins in vitro. Twenty-two (81%) of the patients infected with these 27 isolates had severe disease. Of the eight isolates that did not secrete type III proteins, only three (38%) were cultured from patients with severe disease. Thus, infection with a type-III-secreting isolate correlated with severe disease (p < .05). In vitro assays indicated that ExoU, the type III effector protein most closely linked to mortality in animal models, was secreted in detectable amounts in vitro by 10 (29%) of the 35 examined isolates. Nine (90%) of these 10 isolates were cultured from patients with severe disease (p < .05 when compared with the nonsecreting isolates). In contrast, ExoS was secreted by 16 (46%) of the 35 examined isolates. Twelve (75%) of these 16 isolates were cultured from patients with severe disease (p = .14 when compared with the nonsecreting isolates). In patients with ventilator-associated pneumonia, type-III-secreting isolates were associated with worse clinical outcomes, suggesting that this secretion system plays an important role in human disease. Our findings support the hypothesis that antibodies targeted against these proteins may be useful as adjunctive therapy in intubated patients with P. aeruginosa colonization or infection.