Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparison of a Serum Procalcitonin (PRO-CT) Guided Treatment Plan With the Standard Guideline Recommended Antibiotic Treatment Plan for Patients Hospitalized With a Diagnosis of Exacerbation of COPD
Brief Summary: Exacerbations of chronic obstructive pulmonary disease (COPD) are the first cause of admission to Pulmonary Department in Italy and worldwide. Guidelines recommend treating most patients hospitalized for exacerbations of COPD with antibiotics, even if the role of bacterial infection is often uncertain and the effect of antibiotics poor. The recommendation to use antibiotics is guided by clinical signs and symptoms that have an insufficient diagnostic accuracy, whereas serum biomarkers as procalcitonin (PRO-CT) may guide the selection of COPD patients who need antibiotic treatment. The main aim of the study is to investigate whether antibiotics can be safely stopped after 3 days or continued for 10 days according to a PRO-CT-guided algorithm in patients hospitalized for exacerbations of COPD for whom guidelines recommend 3-10 days antibiotic treatment based on presence of increased dyspnoea, sputum and purulence. The study is designed to assess the non inferiority of the PRO-CT guided plan as compared to the standard guideline recommended plan. The PRO-CT guided withholding of antibiotics is viewed as an experimental intervention associated with less antibiotic-associated complications, eg antibiotic resistance and drug-related side-effect and lower costs. The proposed study is a prospective, randomised controlled, single-blinded intervention trial comparing the standard with a PRO-CT guided antibiotic treatment plan. Patients will be recruited from the Pulmonary Department of 18 University or City Hospitals in Italy, starting October 2006 and continuing until December 2010. Results expected by end of 2011. The 100 patients randomised to the standard non PRO-CT guided antibiotic treatment plan will continue antibiotics for 10 days, whereas the 100 patients randomised to the PRO-CT guided antibiotic treatment plan will continue for 10 days or stop antibiotics on day 3 depending on PRO-CT levels measured at admission, day 1 and day 2. Serum PRO-CT will be measured in a central laboratory. Patients will be examined at admission, discharge, 10 days, 1, 3 and 6 months. A telephone interview will be obtained at 2, 4 and 5 months. The primary outcome of the study will be the rate of exacerbations. Secondary outcomes will be hospital readmission, admission to ICU, change in FEV1, duration of hospitalization, and death. The sample size was estimated according to the primary outcome of the study.


Options:
A: Inclusion Criteria:

1. Patients 18 years of age or older, admitted from the community or a nursing home with acute (i.e., at least 1 day but less than 28 days) LRTI as the main diagnosis consisting of having at least two of the following:

   * new or increased respiratory signs or symptoms (i.e., cough, sputum production, dyspnea, auscultatory findings of abnormal breath sounds and rales, pleuritic chest pain) with or without inflammatory signs (core body temperature \> 38.0° C, leukocyte count \> 10 or \< 4 x 10\^9 cells L-1).
   * CAP is defined by the presence of LRTI along with a new or increased infiltrate on chest radiograph. Severity scores of CAP (pneumonia severity index \[PSI\] and CURB-65) will be calculated.
   * COPD is defined by post-bronchodilator spirometric criteria according to the GOLD-guidelines as a FEV1/FVC ratio below 70% and the severity categorized into mild (FEV1 \<= 80% of predicted), moderate (50% \>= FEV1 \< 80%), severe (30% \>= FEV1 \< 50%) and very severe (FEV1 \< 30%), respectively. Severity of acute exacerbations of COPD will be graded as proposed. Acute bronchitis is defined as LRTI in the absence of an underlying lung disease or focal chest signs and infiltrates on chest X-ray, respectively. Patients who are on admission judged as having an LRTI but have another final diagnosis, will be classified as "others".
2. Ability to understand verbal and written instructions and informed consent.

Exclusion Criteria:

1. Patients unable to give written informed consent, e.g. with severe dementia or patients not understanding German (or other local language) and no translation (e.g. family members) available.
2. Patients with active intravenous drug use.
3. Severe immunosuppression (e.g. patients infected with human immunodeficiency virus infection and a CD4 count below 350 x 10\^9/L, patients on immunosuppressive therapy after solid organ transplantation and neutropenic patients with present neutrophil count \< 500 x 10\^9/L and patients under chemotherapy with neutrophils 500-1000 x 10\^9/L with an expected decrease to values \< 500 x 10\^9/L); patients with cystic fibrosis, infection with M. tuberculosis, L. pneumophila, Listeria spp. hospital stay within 14 days of inclusion.
4. Accompanying chronic (e.g. osteomyelitis), abscess (e.g. brain, pleural empyema) infection or endocarditis.
5. Terminal and very severe medical co-morbidity where death is imminent or has to be expected in the current hospitalization (e.g. due to malignancy, cardiac, renal or hepatic failure, comfort therapy).
B: Inclusion Criteria:

* Severe sepsis or septic shock according to ACCP/SCCM criteria
* Onset of severe sepsis or septic shock \<24 h
* Age \>= 18 years
* Informed consent

Exclusion Criteria:

* Pregnant or breast-feeding women
* Fertile female women without effective contraception
* Participation in interventional clinical trial within the last 30 days
* Current participation in any study
* Former participation in this trial
* Selenium intoxication
* No commitment to full patient support (i.e. DNR order)
* Patient's death is considered imminent due to coexisting disease
* Relationship of the patient to study team member (i.e. colleague, relative)
* Infection where guidelines recommend a longer duration of antimicrobial therapy (i.e. endocarditis, tuberculosis, malaria etc)
* Immunocompromised patients
C: Inclusion Criteria:

* Age over 18 years old
* receiving antibiotics for no more than 24 hours for an assumed or proven infection
* Informed consent

Exclusion Criteria:

* Failure to obtain written consent to participate
* Patients receiving prolonged antibiotic therapies (\> 3 weeks, e.g. endocarditis, cerebral/hepatic abscess)
* Patients with severe infections due to viruses or parasites (e.g. Dengue, Toxoplasma gondii, Plasmodium spp.)
* Patients infected with Mycobacterium tuberculosis
* Patients entering the ICU for post-operative observation and/or on antibiotic prophylaxis with an estimated length of stay less then 24 hrs.
* Patients suffering from cystic fibrosis
* Severely immunocompromised patients such as patients with HIV and with a CD4 count of less than 200 cells/mm, neutropenic patients (\<500 neutrophils per mL) or patients with solid organ transplantation
* Moribund patients
D: Inclusion Criteria:

* Male and female patients who give written informed consent
* Age: adults \>18 years old
* COPD diagnosis according to GOLD guidelines: FEV1/FVC \<70% with FEV1\<80% of predicted. If a COPD diagnosis is not evident from previous spirometric exams of the patient, a new spirometry will be obtained within 3 days of admission and a diagnosis of COPD will be made if all of the following conditions are true: 1) FEV1/FVC \<70% with FEV1 \<80% of predicted; 2) history of cigarette smoking; 3) exclusion of bronchial asthma diagnosis. At the end of the study (i.e. at 6 months) a new spirometric exam will be obtained from these patients to confirm the new diagnosis of COPD made at admission.
* Diagnosis of COPD exacerbation:

  * defined as acute-onset dyspnoea and/or cough associated with increased purulent sputum production (ANTHONISEN criteria)
  * requiring, according to guidelines (GOLD 2005), treatment with antibiotic
  * requiring hospitalization

Exclusion Criteria:

* Female subjects: pregnant, lactating mother or lack of efficient contraception in a subject with child-bearing potential (e.g. contraceptive methods other than oral contraceptives, IUD, tubal ligation)

  * Diagnosis of bronchial asthma
  * Coexisting medical conditions: unstable concomitant cardiovascular, renal, hepatic, gastrointestinal, neurological, endocrine, metabolic, muscle-skeletal, neoplastic, respiratory or other clinically significant disease (patients with stable and well controlled hypertension or diabetes may be included in the study)
  * Clinical significant laboratory abnormalities indicating unstable concomitant disease
  * Patients in whom survival for at least 1 year is unlikely
  * Inability to give informed consent

Answer: D