Catharina F. M. Linssen

C-reactive protein and procalcitonin concentrations in bronchoalveolar lavage fluid as a predictor of ventilator-associated pneumonia

Abstract Background Diagnosis of ventilator-associated pneumonia (VAP) is difficult. The usefulness of high-sensitivity procalcitonin (ProCa-S) and high-sensitivity C-reactive protein (CRPH) in bronchoalveolar lavage (BAL) fluid and serum in the prediction of VAP was determined. Methods The study was conducted over a 28-month period (November 1999–June 2002) at the University Hospital Maastricht. BAL fluid samples were collected from patients admitted to the intensive care unit. Differential cell count and quantitative culture of BAL fluid were performed. C-reactive protein (CRP) and procalcitonin (PCT) on BAL fluid were determined by means of two high-sensitivity kits (CRPH and ProCa-S, respectively). Since both kits were designed for use on serum, validation for use on BAL fluid was performed. Results A total of 117 patients were included. 43.6% (51/117) had microbiologically confirmed VAP. Both CRPH and ProCa-S showed good matrix effect, linearity and intra- and inter-assay variation. No significant differences in PCT and CRP concentrations in serum and BAL fluid were found between the VAP and the non-VAP group. Conclusions Both the ProCa-S and the CRPH kits can be used for assessing the concentration of PCT and CRP in BAL fluid, respectively. PCT and CRP concentrations in BAL fluid appeared to be of no additional value in the diagnosis of VAP.

Variant VKORC1 and CYP2C9 alleles in patients with diffuse alveolar hemorrhage caused by oral anticoagulants.

AbstractBackground: Diffuse alveolar hemorrhage (DAH) is a life-threatening bleeding complication that can occur as a result of oral anticoagulation therapy. Objective: We hypothesized that in patients treated with coumarins, alveolar hemorrhage is associated with vitamin K epoxide reductase (VKORC1) and cytochrome P450 (CYP) 2C9 (CYP2C9) variant alleles. In addition, in the case of acenocoumarol use, CYP2C19 allelic variants also play a role. Methods: During a 7-year period, data on patients using coumarins with confirmed DAH were gathered. Of 173 confirmed DAH cases, 75 received oral anticoagulants, and 63 (84%) of these 75 patients were included because their DNA was available. For genotyping the CYP2C9*2 (430C>T), CYP2C9*3 (1075A>C), CYP2C19*2 (681G>A), CYP2C19*3 (636G>A), VKORC1 (−1639G>A), and VKORC1 (1173C>T) single nucleotide polymorphisms (SNPs), real-time PCRs were performed. Results: In 62 (98.4%) of 63 patients with DAH, variant alleles were found. In 51 (81.0%) of the 63 patients, VKORC1 allelic variants (20 homozygotes and 31 heterozygotes) were present. In 31 (49.2%) of the 63 DAH cases, CYP2C9 allelic variants (three homozygotes, 26 heterozygotes, and two compound heterozygotes) were observed, and in 20 (32.0%) of the 63 patients, variant alleles of both genes were observed. Conclusion: Genotyping of four SNPs for VKORC1 and CYP2C9 polymorphisms is useful in predicting a high probability of the occurrence of DAH in patients receiving oral anticoagulants. Early and timely use of genotyping is recommended to prevent a fatal outcome and to provide safer and more individualized anticoagulant therapy.

Endotracheal Aspirate and Bronchoalveolar Lavage Fluid Analysis: Interchangeable Diagnostic Modalities in Suspected Ventilator-Associated Pneumonia?

ABSTRACT Authoritative guidelines state that the diagnosis of ventilator-associated pneumonia (VAP) can be established using either endotracheal aspirate (ETA) or bronchoalveolar lavage fluid (BALF) analysis, thereby suggesting that their results are considered to be in accordance. Therefore, the results of ETA Gram staining and semiquantitative cultures were compared to the results from a paired ETA-BALF analysis. Different thresholds for the positivity of ETAs were assessed. This was a prospective study of all patients who underwent bronchoalveolar lavage for suspected VAP in a 27-bed university intensive care unit during an 8-year period. VAP was diagnosed when ≥2% of the BALF cells contained intracellular organisms and/or when BALF quantitative culture revealed ≥104 CFU/ml of potentially pathogenic microorganisms. ETA Gram staining and semiquantitative cultures were compared to the results from paired BALF analysis by Cohens kappa coefficients. VAP was suspected in 311 patients and diagnosed in 122 (39%) patients. In 288 (93%) patients, the results from the ETA analysis were available for comparison. Depending on the threshold used and the diagnostic modality, VAP incidences varied from 15% to 68%. For the diagnosis of VAP, the most accurate threshold for positivity of ETA semiquantitative cultures was moderate or heavy growth, whereas the optimal threshold for BALF Gram staining was ≥1 microorganisms per high power field. The Cohens kappa coefficients were 0.22, 0.31, and 0.60 for ETA and paired BALF Gram stains, cultures, and BALF Gram stains, respectively. Since the ETA and BALF Gram stains and cultures agreed only fairly, they are probably not interchangeable for diagnosing VAP.

Mimivirus is not a frequent cause of ventilator-associated pneumonia in critically ill patients.

Acanthamoeba polyphaga mimivirus (APMV) belongs to the amoebae‐associated microorganisms. Antibodies to APMV have been found in patients with pneumonia suggesting a potential role as a respiratory pathogen. In addition, positive serology for APMV was associated with an increased duration of mechanical ventilation and intensive care unit stay in patients with ventilator‐associated pneumonia. The aim of the present study was to assess the presence of APMV in bronchoalveolar lavage fluid samples of critically ill patients suspected of ventilator‐associated pneumonia. The study was conducted in the intensive care unit of the Maastricht University Medical Centre. All consecutive bronchoalveolar lavage fluid samples obtained between January 2005 and October 2009 from patients suspected of ventilator‐associated pneumonia were eligible for inclusion. All samples were analyzed by real‐time PCR targeting the APMV. A total of 260 bronchoalveolar lavage fluid samples from 214 patients (139 male, 75 female) were included. Bacterial ventilator‐associated pneumonia was confirmed microbiologically in 105 out of 260 (40%) suspected episodes of ventilator‐associated pneumonia (86 patients). The presence of APMV DNA could not be demonstrated in the bacterial ventilator‐associated pneumonia positive or in the bacterial ventilator‐associated pneumonia negative bronchoalveolar lavage fluid samples. Although suspected, APMV appeared not to be present in critically ill patients suspected of ventilator‐associated pneumonia, and APMV does not seem to be a frequent cause of ventilator‐associated pneumonia. J Med. Virol. 85:1836–1841, 2013.

Candida Pneumonia in Intensive Care Unit

It has been questioned if Candida pneumonia exists as a clinical entity. Only histopathology can establish the definite diagnosis. Less invasive diagnostic strategies lack specificity and have been insufficiently validated. Scarcity of this pathomechanism and nonspecific clinical presentation make validation and the development of a clinical algorithm difficult. In the present study, we analyze whether Candida pneumonia exists in our critical care population. We used a bronchoalveolar lavage (BAL) specimen database that we have built in a structural diagnostic approach to ventilator-associated pneumonia for more than a decade consisting of 832 samples. Microbiological data were linked to clinical information and available autopsy data. We searched for critically ill patients with respiratory failure with no other microbiological or clinical explanation than exclusive presence of Candida species in BAL fluid. Five cases could be identified with Candida as the likely cause of pneumonia.

Surveillance cultures in healthcare-associated pneumonia: sense or nonsense?

Purpose of review This review explores the usefulness of surveillance cultures in healthcare-associated pneumonia (HCAP). Recent findings The definition of HCAP is controversial. Causative micro-organisms of HCAP resemble those found in hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Some types of surveillance cultures have proven useful in hospitalized patients. Whereas numerous studies have investigated the role of surveillance cultures in VAP, one may wonder whether surveillance culture implementation should belong in HCAP management guidelines. Summary Studies exploring the usefulness of obtaining surveillance cultures in VAP are numerous, but are mostly retrospective, observational and/or quasi-experimental in nature. Surveillance cultures may be useful for antibiotic guidance, but positive predictive value and specificity of surveillance cultures are low, obviously negatively impacting on cost effectiveness, especially in the large population at risk for HCAP. On the other hand, multidrug-resistance is increasing and surveillance cultures for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci in ICU-admitted patients appeared useful and cost-effective. Furthermore, surveillance cultures for the presence of multidrug-resistant Gram-negative bacilli might be useful for antibiotic guidance. Currently, neither community-acquired pneumonia, HCAP, HAP nor VAP guidelines incorporate surveillance cultures. In the future, surveillance cultures in populations at risk for HCAP may be able to differentiate HCAP from other kinds of pneumonia and authorize its reason for existence.

Positive cultures from cardiopulmonary bypass: prevalence and relevance regarding postoperative infection

OBJECTIVE Postoperative infections due to cardiopulmonary bypass (CPB) are associated with high morbidity and mortality. The value of positive cultures taken from CPB priming fluid and CPB blood samples, however, is unclear. This study investigates the epidemiology of positive cultures from CPB and their relation to the occurrence of postoperative infection. METHODS The study was conducted at the Maastricht University Medical Centre, a 715-bed teaching hospital with 900-1000 surgeries requiring CPB annually. From 1 January 1998 until 31 March 2010, all patients with positive CPB cultures drawn either from priming fluid or blood were retrospectively studied. Second, 335 patients with a positive CPB culture were compared with 335 randomly assigned patients who underwent cardiovascular surgery using CPB and had negative CPB cultures. Patients with active endocarditis were excluded. Demographic data and perioperative parameters were documented. Outcome measures were: a relevant infection (acute infectious valve endocarditis, wound infection, intravascular catheter-related infection, and bloodstream infection), occurrence of fever of unknown origin, and 30-day mortality. RESULTS A total of 21840 cultures were analyzed, half being priming fluid and half CPB blood cultures. As many as 111 out of 10920 (1.0%) priming fluid cultures and 598 out of 10920 (5.6%) blood cultures tested positive. Gram-positive cocci predominated both priming fluid and blood cultures. Relevant postoperative infections within 30 days after surgery were seen in 47/663 (7.1%) of patients overall, in 27/330 in the CPB-culture-positive group (8.2%) and 20/333 in the CPB-culture-negative group (6.0%), p=0.275. As many as 38 out of 363 patients (5.7%) were affected by fever of unknown origin (CPB-culture-positive group 4.5%, and CPB-culture-negative 6.9%; p=0.191). The 30-day mortality was 16/330 (4.8%) in the CPB-culture-positive group and 13/333 (3.9%) in the CPB-culture-negative group (p=0.552). CONCLUSIONS Positive cultures from both CPB priming fluid and CPB blood samples were not a rarity and mainly involved skin bacteria, arguing that contamination may have played a role. The risk of postoperative infection within 30 days after surgery was not increased in CPB-culture-positive patients. Therefore, no evidence was found to support routine culturing of CPB samples in patients undergoing cardiothoracic surgery.

Human metapneumovirus in bronchoalveolar lavage fluid of critically ill patients with suspected pneumonia

Dear Editor, Respiratory infections are a major cause of morbidity and mortality worldwide. Although the clinical features are easily recognized, the cause of a large proportion of respiratory infections, especially in immunocompromised patients, remains unknown. Bronchoalveolar lavage (BAL) cytological analysis and culture is routinely used in the assessment of various lung diseases. However, BAL fluid (BALF) analysis does not always result in identification of a causative organism. Since its discovery in 2001, human metapneumovirus (hMPV) has been shown to be the cause of respiratory tract disease worldwide [1]. However, it is very difficult to culture and thus may have been missed as a causative agent in the past. Therefore we performed a study to investigate the presence of hMPV in critically ill patients suspected of hospital-acquired pneumonia (HAP). The study was performed in the 18-bed general intensive care unit (ICU) of the Maastricht University Medical Centre in The Netherlands. All consecutive BALF samples obtained from critically ill patients clinically suspected of HAP were included. An in-house real-time polymerase chain reaction (PCR) was used for detection of hMPV RNA. Between January 2005 and December 2010, 348 BALF samples from 290 patients were included in the study. Human metapneumovirus RNA was detected in 6 out of 348 (1.7%) BALF samples. All six patients were immunocompromised and developed respiratory insufficiency necessitating ICU admittance. However, BAL performed during their stay in the ICU did not reveal bacterial HAP. In one patient, BAL fluid yielded a low load of Candida species; however, this was deemed an unlikely cause of the suspected pulmonary infection (Table 1). The results of our study are supported by those of previous studies. Human metapneumovirus could be

Alternative diagnosis in the putative ventilator-associated pneumonia patient not meeting lavage-based diagnostic criteria

Abstract Background: The clinical picture of ventilator-associated pneumonia (VAP) can be mimicked by other infectious and non-infectious diseases. The aim of this study was to determine the alternative diagnoses and to develop a diagnostic flow chart for patients suspected of having VAP not meeting the diagnostic broncho-alveolar lavage (BAL) criteria. Methods: Adult intensive care patients with a clinical suspicion of VAP and negative BAL results were included. The clinical suspicion of VAP was based on the combination of clinical, radiological, and microbiological criteria. BAL was considered positive if cell differentiation revealed ≥ 2% cells with intracellular organisms and/or quantitative culture results of ≥ 104 cfu/ml. The most likely alternative diagnosis of fever and pulmonary densities was retrospectively determined by two authors independently. Results: In all, 110 of 207 patients with suspected VAP did not meet the diagnostic BAL criteria and required further diagnostic evaluation. In 67 patients an alternative diagnosis for fever could be found. In 51 patients an alternative diagnosis of both fever and pulmonary densities could be established. In almost 40% of patients no alternative diagnosis could be provided. Non-bacterial pneumonia was diagnosed in 10 patients with Herpes simplex virus 1 (HSV-1) as the most common pathogen. In eight patients non-infectious pneumonitis was diagnosed. Conclusion: Due to the wide range of alternative diagnoses and applied tests the diagnostic work-up proved to be necessarily individualized and guided by repeated clinical assessment. The most frequently found alternative diagnoses were viral pneumonia and non-infectious pneumonitis.

Stenotrophomonas maltophilia ventilator-associated pneumonia. A retrospective matched case-control study

Abstract Background: Stenotrophomonas maltophilia is increasingly identified in critically ill patients, but it is considered a pathogen with limited pathogenicity and it is therefore infrequently targeted. This study explores whether S. maltophilia may cause ventilator-associated pneumonia (VAP) and whether it affects intensive care unit (ICU) mortality and 28-day mortality when compared to VAP caused by other Gram-negative bacilli. Methods: Retrospective analysis of a 19-year prospectively collected database. Stenotrophomonas maltophilia as a cause was considered in VAP-suspected cases when S. maltophilia growth of ≥104 cfu/ml was detected in bronchoalveolar lavage fluid analysis. Cases were matched on hospital, gender, age and acute physiology and chronic health evaluation II score in a 1:3 ratio with controls from the same database suffering from VAP caused by other Gram-negative bacilli. Results: Eight cases met the inclusion criteria, of which three were labelled as ‘probable’ SM-VAP and three as ‘possible’ SM-VAP. These six patients constitute 1.8% of all VAPs in the studied period. No significant differences in baseline characteristics and duration of mechanical ventilation (p = 0.68), length of stay in the ICU (p = 0.55) and hospital (p = 0.84) between cases and controls were identified between cases and controls. Intensive care unit mortality odds ratio was 1.7 (p = 0.55; 95% CI 0.3–10.5) and 28-day mortality odds ratio was 1.4 (p = 0.70; 95% CI 0.2–9.1). Conclusions: Stenotrophomonas maltophilia is a possible, yet infrequent cause of VAP. No outcome differences were found when compared to matched VAP caused by other Gram-negative bacilli.