ICU · Antimicrobial Stewardship
Acute severe community-acquired pneumonia: antimicrobial de-escalation and stewardship
Also known as Antibiotic stewardship in CAP · Procalcitonin-guided therapy · De-escalation in pneumonia
Antimicrobial de-escalation is narrowing or stopping antibiotics based on culture results and clinical response. For severe CAP: start broad (ceftriaxone + azithromycin), then narrow at 48-72h based on: (1) culture results (sputum, blood, urinary antigens), (2) clinical response (improving fever, WBC, oxygenation, inflammatory markers), (3) procalcitonin trend. Procalcitonin-guided algorithm: stop antibiotics when procalcitonin <0.25 ng/mL or drops 80% from peak. Duration: 5-7 days for most CAP (7-14 for Legionella, Pseudomonas, S. aureus). Stewardship principles: right drug, right dose, right duration, right route. Avoid: unnecessary broadening, prolonged courses, duplicate coverage.
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Target exams
Red flags
Procalcitonin-guided algorithm
Procalcitonin algorithm for antibiotic duration in CAP
Baseline procalcitonin (on admission)
Procalcitonin (PCT) is a biomarker for bacterial infection. Elevated in bacterial infection (normal <0.1 ng/mL). More specific than CRP (PCT not elevated by viral infection, inflammation alone, or stress). Measure on admission, then daily for first 3-5 days. Trend is more important than absolute value.
Day 3-5 review
Check procalcitonin trend. If PCT dropped >80% from peak OR PCT <0.25 ng/mL: STOP antibiotics. If PCT still elevated (>0.25 ng/mL): continue antibiotics, recheck daily. If PCT rising: reassess — ongoing infection, wrong organism, complication (abscess, empyema), secondary infection.
Clinical assessment alongside PCT
Procalcitonin is an ADJUNCT to clinical assessment — not a replacement. Also assess: temperature trend (afebrile >48h), WBC normalising, improving oxygenation, reducing infiltrates on CXR, reducing inflammatory markers (CRP). If PCT low but patient clinically unwell: continue antibiotics (PCT may be false negative in: localised infection without bacteraemia, early infection, immunosuppression).
Stopping criteria
Stop antibiotics when: (1) PCT <0.25 or >80% drop from peak, AND (2) clinically improving (afebrile, stable vitals, improving inflammatory markers). Duration typically: 5-7 days for most CAP. Exceptions: Legionella (14 days), Pseudomonas (7-14 days), S. aureus including MRSA (14 days), complicated (abscess, empyema — drain-dependent).
Empiric therapy principles — cover the pathogens that kill
The empiric regimen in severe CAP is built on ONE principle: cover S. pneumoniae AND the atypicals from the very first dose. Failure to provide adequate atypical cover in severe CAP is associated with excess mortality; this is the single most-tested stewardship concept. The first antibiotic dose should be given within 1 hour of recognition of severe CAP / sepsis — every hour of delay in septic shock increases mortality.[6]
The two validated empiric regimens for inpatient CAP
| Regimen | Agents | What it covers | Comments |
|---|---|---|---|
| Beta-lactam + macrolide (preferred) | Ceftriaxone 1-2 g IV OD (or ampicillin 1-2 g IV q6h, or benzylpenicillin) PLUS azithromycin 500 mg IV/PO OD (or clarithromycin 500 mg BD) | S. pneumoniae, H. influenzae, M. catarrhalis, and the atypicals — Mycoplasma, Legionella, Chlamydophila | Best outcome data in severe CAP; macrolide adds immunomodulatory / anti-inflammatory effect. The default regimen when renal function and QT interval permit |
| Respiratory fluoroquinolone monotherapy | Moxifloxacin 400 mg IV/PO OD (or levofloxacin 750 mg OD) | All of the above in a single agent — excellent pneumococcal AND atypical cover | Reserve for beta-lactam allergy. CAUTION: QT prolongation, tendinopathy, aortic dissection, C. difficile, dysglycaemia; does NOT cover MRSA or Pseudomonas |
Why use BOTH a beta-lactam AND an atypical together? In bacteraemic pneumococcal pneumonia, dual therapy (beta-lactam + macrolide) has lower mortality than a beta-lactam alone — partly additive cover, partly the macrolide's immunomodulation. The macrolide or fluoroquinolone is also the only agent that reliably treats Legionella, which is rapidly fatal if missed.[6]
Building the empiric regimen at the bedside
Step 1 — Give the first dose within 1 hour
Draw blood cultures (x2) FIRST if it can be done without delaying therapy, but NEVER delay antibiotics >1 h to wait for cultures. Early appropriate antibiotics in septic shock reduce mortality hour by hour — the hour-1 bundle.
Step 2 — Core cover: beta-lactam + macrolide
Ceftriaxone 2 g IV OD + azithromycin 500 mg IV OD is the default for severe CAP WITHOUT risk factors for resistant organisms. Send pneumococcal and Legionella urinary antigens and a respiratory viral PCR on admission.
Step 3 — Add MRSA cover IF criteria met
Add vancomycin 15-25 mg/kg IV q8-12h (AUC-guided) or linezolid 600 mg IV q12h IF: prior respiratory isolation of MRSA, recent IV antibiotics, IVDU, post-influenza necrotising pneumonia, or a unit with high MRSA prevalence. Do NOT add empirically if these are absent — see MRSA section below.
Step 4 — Add Pseudomonas cover IF criteria met
Use an anti-pseudomonal beta-lactam (piperacillin-tazobactam 4.5 g IV q6-8h, cefepime 2 g IV q8h, or meropenem 1 g IV q8h) INSTEAD of ceftriaxone, PLUS an anti-pseudomonal second agent (ciprofloxacin OR an aminoglycoside) PLUS azithromycin, IF: structural lung disease (bronchiectasis), severe COPD on frequent antibiotics, recent hospitalisation, or known Pseudomonas colonisation.
Step 5 — Document the plan and the STOP criteria
Write the indication, the planned duration, the day-3 review point (cultures + procalcitonin + clinical response), and the de-escalation criteria. An antibiotic without an explicit stop/review date is the commonest stewardship failure — every prescription needs an end-point.
De-escalation based on culture results
De-escalation is narrowing or stopping antibiotics at 48-72 h guided by microbiology and clinical response. It is the cornerstone of stewardship and it is SAFE — it reduces resistance, C. difficile, adverse events, and cost WITHOUT increasing relapse or mortality.[1]
The de-escalation decision at 48-72 hours
Gather the microbiology and clinical data
At 48-72 h collate: blood cultures (x2, drawn before antibiotics — positive in ~10-25% of admitted CAP and ~25-50% of severe CAP), sputum Gram stain and culture, pneumococcal and Legionella urinary antigens, respiratory viral PCR, and any BAL/tracheal-aspirate results. Reassess clinically: temperature, RR, SpO2, BP, WBC, inflammatory markers, radiographic trend.
Pathogen identified → narrow to it
Penicillin-sensitive *S. pneumoniae* bacteraemia: narrow to benzylpenicillin or amoxicillin, stop the macrolide after 48-72 h if there are no atypical features. *Legionella* urinary antigen positive: stop the beta-lactam, continue azithromycin or a fluoroquinolone for 14 days. MSSA: narrow to flucloxacillin/cloxacillin. Any Gram-negative: narrow to the narrowest active agent by sensitivities.
No pathogen identified but responding → narrow / de-escalate
If cultures are negative AND the patient is improving: STOP empiric MRSA cover (vancomycin/linezolid) and STOP anti-pseudomonal cover if it was added, and continue monotherapy (ceftriaxone) OR switch to a narrower oral agent if IV-to-PO criteria are met. The commonest error is continuing "just-in-case" broad cover after negative cultures.
Use procalcitonin as the tie-breaker
If PCT has fallen >80% from peak or is <0.25 ng/mL, STOP antibiotics entirely (see algorithm above). If PCT is still high but the patient looks well, hunt for an alternative source or a complication — empyema, abscess, line infection, secondary nosocomial infection.
Document the de-escalation
Record what was stopped, what it was narrowed to, why, and the new stop date. This closes the stewardship loop and forces a deliberate decision rather than passive continuation — "start broad, narrow fast, stop promptly."
De-escalation by culture / antigen result — the common scenarios
| Culture / antigen result | Action on the regimen | Duration |
|---|---|---|
| S. pneumoniae (penicillin-sensitive) bacteraemia | Narrow to benzylpenicillin / amoxicillin; stop macrolide after 48-72 h if no atypical features | 5-7 days |
| Legionella urinary antigen positive | Stop beta-lactam; continue azithromycin 500 mg OD (or moxifloxacin) | 14 days (7-10 if azithromycin and immunocompetent) |
| MSSA | Switch to flucloxacillin / cloxacillin; stop vancomycin | 14 days (longer if bacteraemia / endocarditis) |
| MRSA pneumonia | Continue vancomycin (AUC-guided) or linezolid | 7-14 days |
| Gram-negative (e.g. K. pneumoniae) | Narrow to the narrowest active agent by sensitivity | 5-7 days |
| All cultures NEGATIVE, clinically responding | Stop MRSA + anti-pseudomonal empiric cover; continue ceftriaxone monotherapy or switch to PO | 5-7 days, guided by PCT |
| Influenza PCR positive | Add/continue oseltamivir; stop antibacterials if bacterial superinfection excluded and PCT low | Oseltamivir 5 days |
Procalcitonin-guided stopping — the PRORATA evidence
Procalcitonin (PCT) is a calcitonin precursor released by extra-thyroidal tissues (lung, liver, kidney) in response to bacterial infection and bacterial endotoxin, and SUPPRESSED by interferon-gamma released during viral infection. This makes it far more specific for bacterial infection than CRP, which rises with any inflammatory stress, surgery, trauma, or autoimmunity.[2]
The PRORATA trial established procalcitonin-guided discontinuation in the ICU as safe and effective, and a large patient-level meta-analysis subsequently showed it carries a small MORTALITY benefit, not just an antibiotic-sparing effect.[3][5]
PRORATA (Bouadma 2010, Lancet) — procalcitonin-guided antibiotic discontinuation in ICU
Design
Multicentre, randomised, open-label, non-inferiority trial; 621 patients in French ICUs with suspected bacterial infection (including severe CAP)
Intervention
Procalcitonin-guided algorithm (stop antibiotics when PCT fell >80% from peak, or to <0.5 ng/mL) vs standard care
Primary outcome
Mortality at day 28 AND number of antibiotic-free days alive at day 28
Key result
PCT-guided patients had MORE antibiotic-free days (14.3 vs 11.6 days, p<0.0001) — ~2.7 extra days off antibiotics. Mortality was NON-INFERIOR at day 28 (21% vs 20%) and day 60 (30% vs 26%), with no excess relapse
Clinical bottom line
A procalcitonin-guided algorithm safely REDUCES antibiotic exposure in the ICU by ~3 days without increasing mortality or relapse. The trial that put PCT-guided stopping into routine ICU practice
Schuetz 2018 — patient-level meta-analysis of procalcitonin in acute respiratory infection (Lancet Infect Dis)
Design
Individual patient-data meta-analysis of 26 randomised trials; 6,708 patients across primary care, ED, and ICU settings
Intervention
Procalcitonin-guided initiation and discontinuation vs usual care
Primary outcome
All-cause mortality at 30 days
Key result
Mortality REDUCED: 8.6% PCT-guided vs 10.0% usual care (adjusted OR 0.83, 95% CI 0.70-0.99). Antibiotic exposure fell by ~2.4 days and antibiotic-related side effects were lower
Clinical bottom line
Procalcitonin guidance does not merely save antibiotics — across 26 trials and 6708 patients it is associated with a SMALL MORTALITY BENEFIT (probably from stopping harmful over-treatment). The most robust evidence base for PCT in respiratory infection
ProHOSP (Schuetz 2009, JAMA) — procalcitonin in lower respiratory tract infection
Design
Multicentre randomised non-inferiority trial; 1,359 patients with LRTI (CAP, acute bronchitis, COPD exacerbation) in ED and ward
Intervention
PCT algorithm (initiate antibiotics only if PCT >0.25; stop when <0.25 or >80% drop) vs standard guidelines
Key result
Mean antibiotic exposure REDUCED across all LRTI (in CAP, ~34.8% reduction in exposure days). Adverse outcomes (death, ICU admission, recurrence) NON-INFERIOR, with a trend toward fewer
Clinical bottom line
Extended PCT-guided stewardship from the ICU to the ED and ward. Safe antibiotic reduction in CAP at the point of the admission decision
Procalcitonin vs CRP as an infection biomarker
| Feature | Procalcitonin (PCT) | CRP |
|---|---|---|
| Source | Extra-thyroidal tissues (lung, liver, kidney) | Hepatocytes |
| Stimulus | Bacterial endotoxin / IL-1β / TNF-α | Any IL-6-driven inflammation |
| Suppressed by | Interferon-gamma → low in viral infection | NOT suppressed by viral infection |
| Onset | Rises within 2-6 h | Rises within 12-24 h |
| Half-life | ~20-24 h (tracks response in near-real-time) | ~48 h (lagging) |
| Specificity for bacterial infection | HIGH | LOW (rises with any stress) |
| False negatives | Localised infection (empyema, abscess), early infection, immunosuppression, neutralised by antibiotics started days earlier | — |
| Role | GUIDE initiation and stopping of antibiotics | Trend as a general inflammatory marker |
Duration of therapy — shorter is safer
The single biggest antibiotic-stewardship change in CAP over two decades is the move from 10-14 days to 5-7 days for uncomplicated disease. Shorter courses are non-inferior for cure and REDUCE resistance selection, C. difficile, and adverse events. The ATS/IDSA 2019 guideline endorses a minimum of 5 days of therapy, stopping once the patient is afebrile 48-72 h AND clinically stable.[6]
Antibiotic duration in CAP — pathogen- and scenario-specific
| Scenario | Duration | Rationale |
|---|---|---|
| Uncomplicated CAP, good response, clinical stability | 5 days | Stop if afebrile 48-72 h AND clinically stable. Multiple trials and the ATS/IDSA 2019 guideline support a minimum of 5 days as sufficient |
| Standard inpatient CAP | 5-7 days | The default range; let PCT and clinical response pick the exact day |
| Legionella pneumophila | 14 days (7-10 if azithromycin and immunocompetent; 21 if severely immunocompromised) | Intracellular organism; relapse risk if undertreated. A fluoroquinolone may allow shorter courses |
| Pseudomonas aeruginosa | 7 days (extend to 14 if complicated / bacteraemic) | Recurrence risk in structural lung disease; ensure source control |
| S. aureus (incl. MRSA) pneumonia | 7-14 days (14 days if bacteraemic; longer if endocarditis) | Necrotising infection; exclude endocarditis with echo if bacteraemic |
| Complicated (abscess, empyema) | Until source control achieved + 1-2 weeks beyond | Drainage is the primary therapy; antibiotics are adjunctive |
| ICU / severe CAP, slow responder | Individualise with PCT | Prolonged courses are NOT mandated by ICU location alone — the disease, not the bed, sets duration |
IV-to-oral switch — the step-down
Switching from IV to oral therapy as soon as the patient can absorb and tolerate it is a core stewardship intervention: it shortens length of stay, reduces line infections, lowers cost, and improves comfort. Several CAP agents have excellent oral bioavailability (fluoroquinolones, linezolid, metronidazole, doxycycline, fluconazole all approach 90-100%).[1]
IV-to-PO switch criteria — all must be satisfied
1. Clinical improvement
Cough, dyspnoea and RR improving; haemodynamically stable (no rising vasopressor requirement); oxygenation stable or improving (able to wean FiO2 and respiratory support).
2. Afebrile for at least 24-48 hours
Temperature <37.8°C sustained for 24-48 h without antipyretics (or defervescence within the expected timeframe for the pathogen).
3. Able to tolerate and absorb oral intake
Tolerating oral diet and fluids, no vomiting, no ileus, no malabsorption, functioning GI tract, not immediately post-major-bowel-surgery.
4. Normalising WBC / inflammatory markers
WBC trending toward normal, CRP/PCT falling — objective evidence the infection is responding, not just subjective improvement.
5. Choose a bioequivalent oral agent
Switch to an oral agent with high bioavailability at an organism-appropriate dose: amoxicillin 1 g tds, amoxicillin-clavulanate 875/125 mg BD, doxycycline 100 mg BD, clarithromycin 500 mg BD, or moxifloxacin / levofloxacin. Do NOT "step down" to a NARROWER class than the IV regimen covered — keep the spectrum, change only the route.
Sequential (IV→PO) therapy — agents and their oral bioavailability
| Agent | Oral bioavailability | Comment for step-down |
|---|---|---|
| Levofloxacin / moxifloxacin | ~99% | Excellent step-down; same dose IV and PO |
| Linezolid | ~100% | The definitive oral option for MRSA/VRE step-down |
| Doxycycline | >90% | Covers atypicals and many CAP pathogens; cheap, oral-only |
| Metronidazole | ~100% | Full oral absorption; used for anaerobes / aspiration |
| Fluconazole | ~90% | Full oral absorption |
| Amoxicillin / amoxicillin-clavulanate | ~75-90% | Workhorse oral step-down for penicillin-sensitive S. pneumoniae |
| Azithromycin / clarithromycin | ~37-55% (azithro); tissue levels high | Tissue concentration far exceeds serum — effective despite lower bioavailability |
| Ceftriaxone | NOT available orally | No oral equivalent — step DOWN to an oral agent (amoxicillin, doxycycline, or a fluoroquinolone) |
MRSA coverage — when to add it and when to stop it
Empiric MRSA cover is NOT routine in CAP. It is added only when the pre-test probability of MRSA is high, and it is STOPPED at 48-72 h if cultures are negative — a definitive, evidence-based de-escalation. Adding vancomycin to every CAP patient drives nephrotoxicity (especially with piperacillin-tazobactam) and resistance without benefit.[6]
When to ADD empiric MRSA cover in CAP
| Factor | Risk of MRSA | Action |
|---|---|---|
| Prior respiratory isolation of MRSA | Very high | Add vancomycin or linezolid empirically |
| Post-influenza pneumonia (necrotising / cavitating) | High (PVL-S. aureus, incl. MRSA) | Add vancomycin / linezolid; send respiratory samples urgently |
| Recent IV antibiotic therapy or hospitalisation (last 90 days) | Moderate-high | Add empirically; review at 48-72 h |
| IVDU | Moderate (S. aureus incl. MRSA, often with septic emboli) | Consider empiric cover |
| Severe CAP in a unit with high MRSA prevalence | Unit-dependent | Per unit protocol; de-escalate aggressively if negative |
| End-stage renal disease on haemodialysis, indwelling lines | Moderate | Consider; remove/replace lines |
| None of the above | Low | Do NOT add empirically — it adds nephrotoxicity, cost, and resistance without benefit |
Vancomycin vs linezolid for MRSA pneumonia
| Feature | Vancomycin | Linezolid |
|---|---|---|
| Class | Glycopeptide | Oxazolidinone |
| Lung / ELF penetration | Poor (~25-30% of epithelial lining fluid) | Excellent (ELF exceeds plasma) |
| Dosing / monitoring | 15-25 mg/kg q8-12h, AUC/MIC-guided TDM (target AUC 400-600 mg·h/L) | 600 mg IV/PO q12h, NO TDM |
| Renal toxicity | Yes (worse with piperacillin-tazobactam) | No |
| Myelosuppression (esp. thrombocytopenia >2 weeks) | No | Yes — check FBC weekly if >10-14 days |
| Serotonin syndrome / MAO-A interaction | No | Yes (reversible MAO-A inhibitor — avoid with serotonergic drugs) |
| Oral step-down | None (no oral formulation) | 100% bioavailability — ideal oral step-down |
| Evidence in MRSA pneumonia | The historical standard | Suggested superiority to vancomycin (Wunderink 2012, post-hoc); not definitive |
MRSA empiric-cover decision and de-escalation
Decide to add
Add empiric MRSA cover ONLY if a risk factor is present (prior MRSA isolation, post-influenza necrotising pneumonia, recent IV antibiotics / healthcare exposure, IVDU, or a high-prevalence unit).
Send the right samples
Sputum / tracheal aspirate / BAL for Gram stain AND culture, blood cultures x2, and (if available) an MRSA nasal PCR — a NEGATIVE MRSA nasal swab has a high negative predictive value for MRSA pneumonia and supports early de-escalation.
Review at 48-72 h
If respiratory and blood cultures are negative for MRSA AND the patient is improving: STOP vancomycin / linezolid. This de-escalation is safe, endorsed by ATS/IDSA, and removes the single biggest source of unnecessary vancomycin-days.
If MRSA confirmed
Continue vancomycin (AUC-guided) or linezolid; prefer linezolid in renal failure, for oral step-down, or where vancomycin lung penetration / MIC creep is a concern. Treat 7-14 days; exclude endocarditis with echocardiography if bacteraemic.
Pseudomonas cover — add only when the risk is real
Pseudomonas aeruginosa is NOT a typical CAP pathogen in immunocompetent hosts. Empiric anti-pseudomonal cover is reserved for patients with specific risk factors and de-escalated at 48-72 h if not grown.[6]
When to ADD empiric anti-Pseudomonal cover
| Factor | Action |
|---|---|
| Structural lung disease (bronchiectasis, cystic fibrosis) | Anti-pseudomonal beta-lactam (piperacillin-tazobactam / cefepime / meropenem) + ciprofloxacin or an aminoglycoside |
| Recurrent severe COPD exacerbations / frequent antibiotics / oral steroid dependence | Consider; check prior sputum cultures |
| Recent hospitalisation or IV antibiotics (last 90 days) | Consider; de-escalate at 48-72 h if negative |
| Known Pseudomonas colonisation | Cover per prior sensitivities |
| None of the above | Standard ceftriaxone + macrolide — Pseudomonas is not expected |
SAQ — Empiric antibiotic de-escalation in severe community-acquired pneumonia
10 minutes · 10 marks
A 64-year-old man (85 kg) is admitted to ICU with a 3-day history of fever, rigors, productive cough and pleuritic chest pain, now with progressive dyspnoea. On examination: T 39.2°C, HR 128, BP 82/48 (MAP 59) on noradrenaline 0.25 mcg/kg/min after 30 mL/kg crystalloid, RR 34, SpO₂ 90% on 15 L non-rebreather, GCS 14. Lactate 4.2 mmol/L, WCC 24.6, creatinine 145 (baseline 88), platelets 110. Chest X-ray shows right middle and lower lobe consolidation with a small parapneumonic effusion. Blood cultures x2 are drawn and sent with sputum, pneumococcal and Legionella urinary antigens, and a respiratory viral PCR. CURB-65 score 4. The examiners ask you to outline your empiric regimen, your plan for de-escalation, and your stopping criteria.
SAQ — Antimicrobial stewardship principles in the ICU
10 minutes · 10 marks
You are the ICU consultant on a tertiary mixed unit. A 72-year-old man is day 9 of his admission for severe CAP complicated by ARDS and AKI. He is currently intubated, on ceftriaxone 2 g IV OD (since admission), piperacillin-tazobactam 4.5 g IV q6h added on day 4 for “possible superinfection,” and vancomycin 1.5 g IV q12h added on day 6 for “possible line infection.” Blood, sputum and urine cultures throughout have been negative. T 37.4°C, WCC 11.2, CRP 60 (down from 280), procalcitonin 0.3 ng/mL (peak 6.4). The pharmacy team asks you to lead an antimicrobial stewardship review.
Clinical pearls
Red flags
Additional exam pearls — beyond the basics
Extended red flags
The one-minute exam answer — severe CAP stewardship end to end
Severe CAP antibiotic stewardship from admission to stop
| Stage | Key action | Target |
|---|---|---|
| 0. Recognise + resuscitate | Severe CAP = ICU; cultures x2, urinary antigens, viral PCR BEFORE antibiotics if feasible | Minutes |
| 1. Empiric therapy <1 h | Ceftriaxone 2 g IV + azithromycin 500 mg IV; ADD vancomycin/linezolid if MRSA risk; ADD anti-pseudomonal beta-lactam if risk | First hour |
| 2. Day 3 review | Cultures + clinical response + procalcitonin trend | 48-72 h |
| 3. De-escalate | Narrow to identified pathogen; STOP MRSA/Pseudomonas cover if cultures negative; use PCT as tie-breaker | 48-72 h |
| 4. IV-to-PO switch | When improving + afebrile 24-48 h + tolerating PO + falling WBC/CRP → bioequivalent oral agent | Day 3-5 |
| 5. Stop | At 5-7 days if clinically stable (longer for Legionella, Pseudomonas, S. aureus); PCT <0.25 or >80% drop supports stopping | Day 5-7 |
References
- [1]Martin-Loeches I, Torres A. Severe community-acquired pneumonia Eur Respir Rev, 2022.PMID 36517046
- [2]Schuetz P, et al. Notum palmitoleoyl-protein carboxylesterase regulates Fas cell surface death receptor-mediated apoptosis via the Wnt signaling pathway in colon adenocarcinoma Bioengineered, 2021.PMID 34402722
- [3]Bouadma L, Luyt CE, Tubach F, et al. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial Lancet, 2010.PMID 20097417
- [4]Schuetz P, Christ-Crain M, Wolbers M, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial JAMA, 2009.PMID 19738090
- [5]Schuetz P, Wirz Y, Sager R, et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis Lancet Infect Dis, 2018.PMID 29037960
- [6]Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America Am J Respir Crit Care Med, 2019.PMID 31573350