Recommendations

Key Recommendations

During periods of high COVID-19 prevalence, consider all patients with cough, fever, or other suggestive symptoms to have COVID-19 until proven otherwise. For management of patients with suspected or confirmed COVID-19 pneumonia, see Coronavirus disease 2019 (COVID-19).

  • Pneumonia due to COVID-19 is not covered in this topic.

Prompt, correct, and adequate antibiotic therapy is critical for the treatment of HAP.[2][72][73] Regimens are based on whether risk factors are present for multidrug-resistant (MDR) pathogens. These risk factors are:[1]

  • Intravenous antibiotic therapy in the preceding 90 days (HAP and ventilator-associated pneumonia [VAP])

  • Septic shock at the time of VAP

  • Acute respiratory distress syndrome preceding VAP

  • Onset of VAP on hospital day 5 or more

  • Acute renal replacement therapy prior to VAP onset.

If any of the above risk factors are present, combination therapy with broad-spectrum agents is indicated.[74]

The use of any antibiotics in the hospital setting should be judicious, as it can influence the development of resistant strains, especially in an intensive care unit (ICU). Outbreaks of MDR, gram-negative pathogens occur due to the overuse of beta-lactams or fluoroquinolones.[75] Overall, if any antimicrobial is given preferred use, then resistance may occur. One study reported an outbreak after the prolonged use of carbapenem antibiotics (20 days) and colistimethate (13 days).[76]

A prespecified antibiotic protocol in patients with a new diagnosis of HAP is not required, but is recommended because it ensures that patients are not undertreated, especially early in the course of treatment when physicians have the opportunity to decrease mortality.[2] A protocol should have a list of drugs from which to choose, and the regimen should subsequently be de-escalated or resistance may increase.

Administer oxygen therapy as necessary. Monitor oxygen saturation and inspired oxygen concentration with the aim of maintaining SaO2 above 92%.[77][78]​​ High concentrations of oxygen can safely be given in uncomplicated pneumonia. Oxygen therapy in patients with COPD complicated by ventilatory failure should be guided by repeated arterial blood gas measurements.[77] Patients with respiratory failure despite appropriate oxygen therapy require urgent airway management and possible intubation. For conscious patients with an intact airway and escalating oxygen requirements, high flow nasal cannula oxygen therapy or noninvasive ventilation can be considered.[79][80][81]​ See Acute respiratory failure.​

Assess volume status, paying particular attention to signs of volume depletion. Administer intravenous fluids as needed, and give nutritional support in prolonged illness.

Empiric antibiotic therapy

Empiric antibiotic regimens should always be adapted to local patterns of resistance; an antibiogram should be consulted.[74]

If a patient has no risk factors for MDR pathogens, the causative pathogen of the pneumonia is likely to be Streptococcus pneumoniae, Haemophilus influenzae, methicillin-sensitive Staphylococcus aureus (MSSA), or antibiotic-sensitive enteric gram-negative bacilli (e.g., Escherichia coli, Klebsiella pneumoniae, Enterobacter species, Proteus species, or Serratia marcescens). Therapy involves monotherapy with coverage for Pseudomonas aeruginosa: cefepime, ceftazidime, imipenem/cilastatin, meropenem, levofloxacin, or piperacillin/tazobactam.[1][82][83] Note the absence of aminoglycosides from this list because they have been deemed to have more risk than benefit, despite their coverage for P aeruginosa-causing HAP/VAP.[84]

If a patient does have risk factors for MDR pathogens, the causative pathogen is likely to be P aeruginosa, K pneumoniae (extended-spectrum beta-lactamase [ESBL] strain), Acinetobacter species, MRSA, or Legionella pneumophila. HAP/VAP due to one of these pathogens has been associated with an increased mortality.[85] Risk factors for P aeruginosa include a high-quality Gram stain with gram-negative bacilli, and structural lung disease. If either of those factors are present or if the patient is mechanically intubated and ventilated, or has septic shock, then combination therapy should be given for P aeruginosa. Therapy for patients likely to have MDR pathogens involves combination therapy with a cephalosporin (e.g., cefepime, ceftazidime), a carbapenem (e.g., imipenem/cilastatin, meropenem), a beta-lactam/beta-lactamase inhibitor (e.g., piperacillin/tazobactam), or a monobactam (e.g., aztreonam); plus a fluoroquinolone (e.g., ciprofloxacin, levofloxacin) or an aminoglycoside (e.g., amikacin, gentamicin, tobramycin); plus linezolid or vancomycin (or, alternatively, telavancin).[83]

If Pseudomonas is suspected to be the causative pathogen, two antibiotics should be used empirically with different modes of action, with regimens consisting of various combinations of antipseudomonal beta-lactams, carbapenems, fluoroquinolones, and aminoglycosides. Imipenem/cilastatin or meropenem (carbapenem antibiotics) could be used, but ertapenem should not be, as it does not cover P aeruginosa and is approved only for community-acquired pneumonia. Empiric treatment with a carbapenem has been associated with lower short-term mortality than treatment with non-carbapenems mainly in patients with VAP; but also with increased resistance, making it harder to escalate an antimicrobial regimen if needed.[86] For multidrug-resistant gram-negative pathogens, ceftazidime/avibactam is a beta-lactam option.[87] Other approved antibiotics with P aeruginosa coverage for patients with HAP/VAP and multidrug-resistant gram-negative pathogen infection include cefiderocol (a novel siderophore cephalosporin), and the combination antibiotics imipenem/cilastatin/relebactam (a carbapenem with a potent beta-lactamase inhibitor) and ceftolozane/tazobactam (a novel beta-lactam/beta-lactamase inhibitor).

Aminoglycosides offer rapid killing of gram-negative bacteria, but may cause renal toxicity or ototoxicity. Tobramycin has slightly better lung penetration than gentamicin, and may be given as an inhaled agent, although this is an emerging treatment. Fluoroquinolones have been efficacious and ciprofloxacin has a relatively narrow spectrum, but resistance to  Pseudomonas increases yearly. Fluoroquinolones have also been associated with Clostridium difficile colitis. Both aminoglycosides and fluoroquinolones are concentration-dependent antimicrobials and are dosed to take advantage of this characteristic with infrequent and high doses, as opposed to time-dependent antimicrobials (e.g., beta-lactams), which are dosed to keep drug levels above the minimum inhibitory concentration. Incidentally, a study comparing tigecycline with imipenem/cilastatin found that it was noninferior in patients with HAP, but inferior in patients with VAP.[88] Tigecycline is currently approved for community-acquired pneumonia, not HAP. Tigecycline now has a boxed warning that states that it should only be used when an alternative agent is not suitable. This is due to increased mortality (0.6%; 95% CI 0.1, 1.2) associated with its use. For VAP patients, the mortality with tigecycline was 50.0% versus 7.7% for the comparator group.[89] Ultimately, regimens should be based on local antibiograms.

Vancomycin or linezolid should be added (i.e., patient will take 3 antibiotics) if the patient has a risk for MRSA infection. Risk factors for MRSA include prior antimicrobial use within the previous days, admission to an ICU where >20% of Staphylococcus aureus isolates are MRSA positive (or the percentage is unknown), and having a high risk for mortality. Data suggest that linezolid and vancomycin are similarly efficacious. Follow-up data are equivocal, suggesting that linezolid and vancomycin are equivalent or that linezolid is superior.[90][91][92][93][94][95]

If HAP is diagnosed after antibiotics have been used recently or while a patient is receiving antibiotics for a different infection, empiric therapy should involve drugs from a different class.

Pathogen-directed antibiotic therapy

Once cultures return, antibiotics should be de-escalated accordingly: treatment should be narrowed based on the sensitivities of what particular pathogen grew, or antimicrobials should be discontinued based on what did not grow. For example, linezolid should be continued if MRSA is cultured, or discontinued if it was not.[96][97]

Examples of antibiotics used for treatment of a confirmed gram-negative infection (e.g., Pseudomonas, Acinetobacter, Klebsiella, Serratia) are a cephalosporin (cefepime, ceftazidime, cefiderocol), or a carbapenem (imipenem/cilastatin, meropenem), or a beta-lactam/beta-lactamase inhibitor (piperacillin/tazobactam), or a fluoroquinolone (ciprofloxacin, levofloxacin), or an aminoglycoside (amikacin, gentamicin, tobramycin), or a polymyxin (colistimethate), or a carbapenem with a potent beta-lactamase inhibitor (imipenem/cilastatin/relebactam), or a cephalosporin with a beta-lactamase inhibitor (ceftazidime/avibactam, ceftolozane/tazobactam). Monotherapy with a single antibiotic should be sufficient. However, 2 drugs in combination can be used if the infection is in a difficult area to penetrate, such as a lung abscess, an empyema, or an accompanying endocarditis. Combination regimens could consist of a cephalosporin (cefepime, ceftazidime), a carbapenem (imipenem/cilastatin, meropenem), or a beta-lactamase inhibitor (piperacillin/tazobactam), plus a fluoroquinolone (ciprofloxacin, levofloxacin), an aminoglycoside (amikacin, gentamicin, tobramycin), or a polymyxin (colistimethate). Ceftazidime/avibactam has been approved for HAP and VAP due to bacteria in adult patients.[87] It has activity against MDR gram-negative pathogens, including ESBL producing bacteria, and  P aeruginosa. In order to prevent global resistance, cephalosporin/beta-lactamase inhibitor combination agents and carbapenems should be reserved for patients with infections that are proven or strongly suspected to be caused by susceptible bacteria, or for high risk patients with MDR.[98]

Traditionally, any pseudomonal infection was treated with two antibiotics. A study in 1989 evaluating patients with  Pseudomonas bacteremia, including some patients with pneumonia, showed a lower mortality among those receiving combination therapy.[99] Since then, studies have shown that results are similar between patients with HAP who have single or combination therapy.[100][101][102] Benefits of monotherapy include fewer adverse events, less resistance, and lower cost.

An example of a gram-positive pathogen that is a common cause of HAP is S aureus. Methicillin-sensitive strains are treated with penicillin or cephalosporin. If the patient is allergic to penicillins, linezolid or vancomycin can be used. Methicillin-resistant strains are treated with linezolid or vancomycin.

If ESBL-producing Enterobacterales are the cause of HAP, then recommended first-line treatment is with a carbapenem antibiotic. Second-line treatment is with a fluoroquinolone.[103] In practice, a third-line treatment is with a carbapenem/beta-lactamase inhibitor or cefiderocol. Ceftolozane/tazobactam also has activity against some ESBLs. A rarely identified cause of HAP is  L pneumophila. Treatment may be with either a fluoroquinolone or a macrolide.

Duration of therapy

Previously, use of the Clinical Pulmonary Infection Score (CPIS) was recommended to aid the decision on whether treatment should be adjusted or discontinued.[104]

However, pooled data from accuracy studies have shown weak evidence to discourage the use of the CPIS to confirm or exclude VAP or to determine the duration of antimicrobial therapy.[1][105]

The latest recommendation for the duration of antibiotic therapy is that it may be completed at 7 days if a patient is clinically and radiologically stable, including laboratory values, and is not infected with Acinetobacter or P aeruginosa; the CPIS does not need to be used.[1][82][106] There are no data supporting longer therapy for MRSA, although it is often practiced; 2 weeks should be given if bacteremia is present, and longer if HAP/VAP is associated with a complication such as an empyema or endocarditis. Patients who received 7 to 8 days of antimicrobials had less recurrent VAP due to MDR pathogens and no differences in mortality, length of hospital stay, treatment failure, and time mechanically intubated and ventilated.[107][108] [ Cochrane Clinical Answers logo ] ​​​​​​​[Evidence B]​​​ The Centers for Disease Control and Prevention (CDC) advises to optimize antibiotic selection and reassess antibiotic treatment when the results of diagnostic testing are available. The CDC also advises to use the shortest effective duration of therapy, as opposed to giving prolonged courses of antibiotics (which has historically been the approach to treating HAP).[109]​ Consequently, most HAP treatment durations may be shorter, but HAP due to Pseudomonas or Acinetobacter should still be treated for 2 weeks.[106]

If no improvement is seen within this time, changing the antibiotic regimen to cover resistant or unusual (e.g., fungal) pathogens should be considered. However, it is also important to evaluate the patient for other pulmonary entities, such as reconsidering whether an effusion may be an exudate (e.g., empyema) instead of a transudate. It is also important to evaluate for other, nonpulmonary sources of infection. A certain procedure may be indicated that was not considered previously, such as an ultrasound of an extremity with an intravenous line in order to rule out septic thrombophlebitis. A bronchoscopy or a thoracentesis may need to be repeated as well. Overall, failure of treatment may be due to:[110]

  • A complication

  • A wrong diagnosis

  • Treatment of the wrong pathogen.

Strategies such as changing ventilator settings to pressure support or using an oscillator mode may be considered by a pulmonologist.

Safety of fluoroquinolones

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[111]

  • Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only.

  • Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics that are commonly recommended for the infection are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.

While fluoroquinolones are no longer licensed for the treatment of nosocomial pneumonia in Europe, they are still approved for this indication in the US and other countries, and guidelines still recommend their use.[1] Therefore, the use of fluoroquinolones is still recommended in this topic, although they should be used with caution.

Response to treatment

Procalcitonin may be used to follow a trend of values starting from the day of diagnosis.​[112] That information may be used to determine when to discontinue antimicrobials.[1]

Supraglottic airway devices: animated demonstration
Supraglottic airway devices: animated demonstration

How to size and insert a laryngeal mask airway.

Nasopharyngeal airway: animated demonstration
Nasopharyngeal airway: animated demonstration

How to select the correct size naspharyngeal airway and insert the airway device safely.

Oropharyngeal airway: animated demonstration
Oropharyngeal airway: animated demonstration

How to size and insert an oropharygeal airway.

Bag-valve-mask ventilation: animated demonstration
Bag-valve-mask ventilation: animated demonstration

How to use bag-valve-mask apparatus to deliver ventilatory support to adults. Video demonstrates the two-person technique.

Tracheal intubation: animated demonstration
Tracheal intubation: animated demonstration

How to insert a tracheal tube in an adult using a laryngoscope.

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