Microbiology and Clinical Outcome of Pneumonia
Microbiology and Clinical Outcome of Pneumonia
1. BACKGROUND

 Pneumonia occurring outside of the hospital setting is regarded as community acquired
 pneumonia. However, pneumonia occurring in non-hospital long-term care facilities
 constituted a distinct type of pneumonia from CAP. Kollef et al has justified health
 care associated pneumonia (HCAP) as a new category of pneumonia [1]. The HCAP patients
 are associated with severe disease, higher mortality rate, and greater length of stay
 and increased cost [1]. HCAP are often at risk for multi-drug resistant bacterial
 pathogens such as Pseudomonas aeruginosa, extended-spectrum beta-lactamase Klebsiella
 pneumoniae, Acinetobacter baumannii, and methicillin-resistant S. aureus (MRSA) [2].

 Health care facilities have not been defined in Taiwan. Respiratory care ward (RCW) is a
 special unit to take care long-term ventilatory dependent patients in Taiwan. Some of
 the patients get pneumonia and are referred back to medical centers. Besides,
 community-acquired P. aeruginosa, Acinetobacter baumannii or MRSA have been reported
 [3-8]. Therefore, the core-organisms of HCAP in Taiwan might be multi-drug resistant and
 the causes of inadequate initial antibiotics treatment. The common pathogens were also
 unknown.

 Till now, there are no data about the pathogens of HCAP in Taiwan. We define the
 health-care facilities and initiate a retrospective study to characterize the
 microbiology and clinical outcome of Community acquired pneumonia and
 Health-Care-Associated pneumonia in Taiwan. Further analysis will perform to confirm the
 differences between CAP an HCAP in Taiwan.

 2. Objectives:

 I. To characterize CAP and HCAP i. Microbiological epidemiology ii. Disease severity:
 PSI iii. Outcome : length of stay, mortality , antimicrobial susceptibility and
 treatment outcomes II. To characterize HCAP from RCW i. Microbiological epidemiology ii.
 Disease severity: PSI iii. Outcome : length of stay, mortality

 3. Study design:

 This is a retrospective multi-center cohort study to characterize microbiology, and clinical
 outcomes in Taiwan.

 Data sources: CAP or HCAP registered in 4 medical centers from Jan 1 2007 to Dec. 31 2007. (2
 in north Taiwan, 1 in central Taiwan, 1 in south Taiwan) Expected case number: 800 HCAP and
 1800 CAP
BACKGROUND

 Pneumonia occurring outside of the hospital setting is regarded as community acquired
 pneumonia. However, pneumonia occurring in non-hospital long-term care facilities constituted
 a distinct type of pneumonia from CAP. Kollef et al has justified health care associated
 pneumonia (HCAP) as a new category of pneumonia . The HCAP patients are associated with
 severe disease, higher mortality rate, and greater length of stay and increased cost - HCAP
 are often at risk for multi-drug resistant bacterial pathogens such as Pseudomonas
 aeruginosa, extended-spectrum beta-lactamase Klebsiella pneumoniae, Acinetobacter baumannii,
 and methicillin-resistant S. aureus (MRSA) Health care facilities have not been defined in
 Taiwan. Respiratory care ward (RCW) is a special unit to take care long-term ventilatory
 dependent patients in Taiwan. Some of the patients get pneumonia and are referred back to
 medical centers. Besides, community-acquired P. aeruginosa, Acinetobacter baumannii or MRSA
 have been reported [3-8]. Therefore, the core-organisms of HCAP in Taiwan might be multi-drug
 resistant and the causes of inadequate initial antibiotics treatment. The common pathogens
 were also unknown.

 Till now, there are no data about the pathogens of HCAP in Taiwan. We define the health-care
 facilities and initiate a retrospective study to characterize the microbiology and clinical
 outcome of Community acquired pneumonia and Health-Care-Associated pneumonia in Taiwan.
 Further analysis will perform to confirm the differences between CAP an HCAP in Taiwan.

 Objectives:

 -  To characterize CAP and HCAP

 -  Microbiological epidemiology

 -  Disease severity: PSI

 -  Outcome : length of stay, mortality , antimicrobial susceptibility and treatment
 outcomes

 -  Microbiological epidemiology

 -  Disease severity: PSI

 -  Outcome : length of stay, mortality

 Study design:

 This is a retrospective multi-center cohort study to characterize microbiology, and clinical
 outcomes in Taiwan.

 Data sources: CAP or HCAP registered in 4 medical centers from Jan 1 2007 to Dec. 31 2007. (2
 in north Taiwan, 1 in central Taiwan, 1 in south Taiwan) Expected case number: 800 HCAP and
 1800 CAP

 Study population:

 Those adult patients (age ≥ 18 y/o) met the criteria of pneumonia are evaluated. The patients
 are enrolled if they meet the following criteria.

 The diagnosis of pneumonia is established within 48h of hospitalization (including time of
 emergency room).

 Pneumonia is defined as clinical suspicion of pneumonia (cough, short of breath, expectorant)
 with new-onset pulmonary infiltrates plus at least one of the following criteria:

 -  Fever (≥38.3 C) or hypothermia (<36.0 C) (axillary temp - 0.5)

 -  Leukocytosis (increase of total WBC > 10,000/cumm); or leukopenia (<4000/cumm) or band >
 10%

 -  Purulent airway secretion (tracheal aspirates, or sputum)

 Etiology diagnosis

 -  Specimens obtained within 72h (sputum, tracheal aspirate, BAL, pleural effusion or
 blood)

 -  Urine antigen test for legionella or Streptococcus at the onset of pneumonia

 -  Paired serology (at admission and within 4th to 8th weeks)

 -  virus culture

 -  Definition of definite pathogen: [9](Resp Med 2005;1079)

 -  Blood culture is accepted if the same microorganism is identified in a respiratory
 specimens and no other source for the positive blood culture could be identified.

 -  The isolate is cultured from pleural effusion.

 -  ≥ 4 x fold risk in IgG antibody titer to L. pneumoniae, C. pneumoniae or to any of
 respiratory virus antigens tested or a seroconversion of antibodies to M. pneumoniae
 based on manufacture's criteria.

 -  M. pneumoniae IgM (+), L. pneumoniae ( IgG higher above 1:128) or C. pneumoniae ( high
 above 1:256) are also defined as definite pathogens.

 -  Detection of L. pneumoniae antigen in urine

 -  Detection of S. pneumoniae antigen in urine or isolation of S. pneumoniae from purulent
 sputum

 -  Bronchoscope guided study: BAL > 104/cfu, PSB > 103/cfu

 -  Sputum or BAL revealing Pneumocystic carinii, Mycobacterium tuberculosis, Cryptococcus
 neoformans

 -  Growth of fungi in the respiratory samples is considered diagnostic only in the presence
 of a concomitant positive blood culture growing the same microorganism (candida,
 Aspergillosis)

 Probable pathogens:

 -  Pathogen was confirmed by the isolatioin of a predominant organism from sputum or
 endotracheal aspirate

 Comorbidity:

 -  Neoplastic disease

 -  Any cancer except basal or squamous cell ca of the skin that was active at the time of
 presentation or diagnosed within one year of presentation

 -  Liver disease

 -  A clinical or histologic diagnosis of cirrhosis or another form of chronic liver disease
 such as chronic active hepatitis

 -  Cardiac comorbid illness:

 -  Systolic or diastolic ventricular dysfunction documented by history, physical
 examination, chest radiograph, echocardiogram, multiple gated acquisition scan or left
 ventriculogram (congestive heart failure New York heart association class III to IV)

 -  Disorders of the central nervous systems

 -  A clinical diagnosis of stroke or transient ischemic attack or stroke documented by MRI
 or CT scan

 -  Presence of symptomatic acute or chronic vascular or nonvascular encephalopathy,
 dementia, parkinsonism, motor neuron disease etc

 Renal:

 -  A history of chronic renal disease or abnormal blood urea nitrogen and creatinine
 concentration documented in the medical record (Cr >2mg/dL)

 -  Pulmonary:

 treatment for asthma, or COPD, or presence of interstitial lung disease, bronchiectasis,
 tuberculosis,

 -  DM

 Lung cancer:

 -  Lung cancer active at the time of presentation or requiring anti-neoplastic treatment
 within the preceding one year.

 -  Autoimmune disease

 -  Treatment for RA, SLE, polymyositis, dermatomyositis etc

 -  Having an immunocompromised state

 -  equivalent to > daily prednisolone 5mg or > prednisolone 150 mg / month

 -  other immunosuppressive medications (cyclophosphamide, cyclosporine etc)

 -  s/p organ transplantation

 Definition of clinical items:

 Altered mental status: disorientation with respect to person, place or time that is not known
 to be chronic, stupor, or coma

 -  Neutropenia:

 -  neutropenia with absolute neutrophil count < 1000

 -  smoking (pack year)

 -  current smoker

 -  exsmoker (quitting for > 6 months)

 -  non-smoker (never smoking)

 -  Septic shock: a persistent arterial hypotension in a septic patient.

 -  Hypotension is defined by a systolic arterial pressure < 90mmHg or Mean arterial
 pressure < 60mmHg after adequate volume resuscitation (>5000 cc fluid resuscitation/day)
 or vasopressor (dopamine > 5mcg/kg/h) to maintain blood pressure.

 -  Acute respiratory failure: need mechanical ventilation support intubation and MV support
 only non-invasive mechanical ventilator

 -  ICU admission: admission to ICU during hospitalization

 -  Length of ICU: days staying in ICU

 -  Hospital days: days staying in the hospital (from ER to hospital discharge) discharge
 status

 -  mortality (including AAD with impending death)

 -  survival

 -  without MV (invasive and non-invasive MV)

 -  tracheostomy

 -  ventilator dependent

 -  Residence after discharge

 -  Home, nursing home, RCW, others

 -  Organ failure:

 -  Respiratory failure（PaO2／FiO2<300 )

 -  Acute renal failure（Cr>2.0 or Cr increase>0.5 ㎎/dl )

 -  Acute liver failure（Total bilirubin>4 ㎎/dl )、

 -  Coagulopathy（INR>1.5 time or aPTT>60 seconds )

 -  Thrombocytopenia（Platelets <100000／CUMM ）

 All parameters required for the calculation of PSI (Pneumonia Severity Index, appendix) at
 baseline will be collected.

 Definition of appropriateness of Empirical therapy Empirical antibiotic therapy is defined as
 antibiotic given during the first 48 hours for pneumonia. The appropriateness of antibiotic
 therapy will be analyzed only for cases with causative organism (probably and definite
 organisms) identified. Inadequacy therapy is defined as administration of an antibiotic to
 which the isolated pathogen was resistant according to the subsequent antimicrobial
 susceptibility results or the absence of antimicrobial agents to cover the identified
 pathogen(s). In addition, patients with aspiration pneumonia (Aspiration pneumonia are
 defined as witnessed aspiration pneumonia and food or material noted in the upper or lower
 airways) who had not received agents with anti-anaerobic coverage will be considered
 inappropriate.

 Definition of Treatment outcomes

 In addition to collecting microbiological response, clinical response data will be used for
 all patients. Success/favorable clinical response will be defined as all or most of
 pretreatment signs and symptoms of the index infection have resolved or improved (e.g.: TPR
 shift toward normal) and no additional antibiotic therapy or switching of regimen was
 required. While failure will be defined as no apparent response to therapy; persistence or
 progression of most/all pre-therapy signs and symptoms and additional antibiotic therapy or
 switching of regimen was documented.

 Cases will be classified as "Indeterminate" when no sufficient data is available to permit
 evaluation of microbiological or clinical outcome or patient's underlying medical condition
 is too complicated to precluded classification as a success or failure.

 Data collection and analysis plan

 Data from all sites will be pooled and combined. Statistical analyses will be conducted with
 the use of SAS software, version 8.2 (SAS Institute Inc., Cary, NC, USA). Data will also be
 presented as mean +/-SD for continuous variables and proportions for categories variables.
 The patient demographics and baseline characteristics will be tabulated. The distribution of
 comorbidities, disease severity, causative organisms, clinical condition and outcomes will be
 summarized and analyzed. To detect the significant differences between groups, Chi-square
 tests or Fisher exact test for categorical variables, and the two-tailed t test or
 Mann-Whitney test for continuous variables will be employed, when appropriate. Statistical
 significance will be established at alpha =0.05. Reported P values will be two-sided.
Inclusion Criteria:

 CAP criteria:

 -  Those pneumonia patients have not been admitted within 14 days before diagnosing
 pneumonia.

 -  Those pneumonia patients are not met the criteria of HCAP criteria as stated below.

 HCAP criteria:

 -  Regular hemodialysis, peritoneal dialysis or infusion therapy (ex TPN, repeated blood
 transfusion etc ) at a hospital or hemodialysis clinic.

 -  Receive radiation therapy or chemotherapy at out-patient clinics within 90 days

 -  to be admitted to an acute care hospital for two or more days within 90 days before
 the onset of pneumonia

 -  Resided in a nursing home or long-term care

 Exclusion Criteria:

 -  The patients with HAP: pneumonia developed two days after admission or within 14 days
 after discharge (except RCW)

 -  VAP: HAP and with mechanical ventilation for at least 48h (except RCW patients)

 -  HIV positive with a CD4+ < 200