Therapy of Aspiration: Out-of-Hospital and In-Hospital-Acquired

Abstract

Therapeutic considerations for aspiration pneumonia prioritize the risk of multidrug-resistant organisms. This involves integrating microbiological insights with each patient's unique risk profile, including the location at the time of aspiration, and whether it occurred in or out of the hospital. Our understanding of the microbiology of aspiration pneumonia has also evolved, leading to a reassessment of anaerobic bacteria as the primary pathogens. Emerging research shows a predominance of aerobic pathogens, in both community and hospital-acquired cases. This shift challenges the routine use of broad-spectrum antibiotics targeting anaerobes, which can contribute to antibiotic resistance and complications such as Clostridium difficile infections—concerns that are especially relevant given the growing issue of antimicrobial resistance. Adopting a comprehensive, patient-specific approach that incorporates these insights can optimize antibiotic selection, improve treatment outcomes, and reduce the risk of resistance and adverse effects.

Keywords

aspiration pneumonia - community-acquired aspiration - in-hospital aspiration - chemical pneumonitis - antibiotic therapy

Recent advancements in our understanding of aspiration pneumonia and its pathobiology have prompted a more refined approach to its management. Treatment strategies currently incorporate a range of factors, including the aspiration event's timing and location (community-acquired vs. hospital-acquired) and the patient's overall risk profile for multidrug-resistant organisms (MDROs). For instance, the prevalence of antibiotic-resistant bacteria in hospital settings often necessitates broader-spectrum antibiotic therapy for hospital-acquired aspiration pneumonia (HAAP), while narrower-spectrum agents are generally suitable for community-acquired cases.[1] [2] [3] Furthermore, the role of anaerobic bacteria in aspiration pneumonia has been reevaluated, with a shift away from routine coverage in light of evolving microbiological and clinical data.[4]

In this review, we examine contemporary treatment strategies for aspiration pneumonia, informed by the latest evidence and guidelines. We discuss the impact of microbiological factors on therapeutic decisions, outline treatment algorithms, explore the role of adjunctive therapies, and address the related condition of chemical pneumonitis.

Classification of Aspiration Pneumonia

Aspiration refers to the inhalation or entry of foreign contents, typically oropharyngeal or gastric contents, into the airway and lower respiratory tract.[5] While both micro- and macro-aspiration can lead to the development of pneumonia, the term aspiration pneumonia is typically reserved for bacterial infection that develops after a witnessed or presumed macro-aspiration event, leading to the inoculation of bacteria into the lungs.[4]

Since aspiration is a central mechanism in the development of pneumonia, aspiration pneumonia can be viewed as part of a broader spectrum of bacterial lung infections that can be classified into out-of-hospital or community-acquired aspiration pneumonia (CAAP), and HAAP. CAAP is defined as pneumonia that develops after a witnessed or presumed aspiration that occurs outside of a hospital setting.[1] Conversely, HAAP is an infection that develops after a witnessed or suspected aspiration during hospitalization, typically greater than 48 hours from the initial event.[2] [3] The distinction between these categories, while clinically relevant due to differences in typical pathogens, is increasingly obscured by the growing prevalence of MDROs in both settings.[6] [7] [8] [9] Consequently, the choice of antibiotic therapy may ultimately depend on the patient's overall risk profile for MDROs rather than solely on the location and timing of aspiration.

Chemical pneumonitis, also known as aspiration pneumonitis, is another significant clinical condition resulting from macro-aspiration. It involves the aspiration of toxic fluids, most commonly from gastric origin, into the airway.[10] First described by Mendelson in 1946, the severity of chemical pneumonitis can vary, ranging from low-grade fever and cough to severe bronchospasm and the development of acute respiratory distress syndrome (ARDS).[11] [12] [13] [14]

Severe chemical pneumonitis can result in significantly reduced lung compliance marked by micro-atelectasis, peribronchial hemorrhage, edema, and degeneration of bronchial epithelial cells. Neutrophilic inflammation follows, with the development of hyaline membranes within 48 hours.[12] [15] [16] This inflammatory cascade involves TNF-α, TGF-β, histamines, and leukotrienes leading to alveolar epithelial changes.[17] [18] The acidity and volume of the inoculum are essential elements that directly influence the severity of the subsequent syndrome.[15] [19] In murine models, gastric pH <2.5 and volumes >1 to 4 mL/kg are significant enough to cause acute lung injury.[19]

A key distinguishing feature between chemical pneumonitis and aspiration pneumonia is the timing of onset. Despite overlapping features, symptoms of chemical pneumonitis typically appear within 2 hours of the inciting event and tend to be more abrupt.[11] [14] Differentiating chemical pneumonitis from aspiration pneumonia is crucial, as chemical pneumonitis relies primarily on best supportive care.[4] [5] Empiric antibiotic therapy for chemical pneumonitis is currently not recommended, as data demonstrating clinical benefit are limited.

Microbiological Considerations in Aspiration Pneumonia Therapy

Community-Acquired Aspiration Pneumonia

The predominant pathogens responsible for CAAP mirror those of community-acquired pneumonia (CAP), which include Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Group A Streptococci.[20] [21] However, studies have shown that MDROs, such as Pseudomonas aeruginosa, Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus (MRSA), can also be present in CAP. In a prospective study of CAP patients in Barcelona, Spain, the prevalence of P. aeruginosa, Enterobacteriaceae, and MRSA was estimated to be up to 6%.[6] It is also important to note that distinct microbiomes with corresponding potentially pathogenic organisms exist worldwide. For example, in Southeast Asia, there is a higher carriage of gram-negative bacilli such as Pseudomonas, Klebsiella, and Acinetobacter species within the healthy nasopharynx, which is then mirrored in the lower airways.[22] [23] Additionally, the severity of pneumonia may indicate a higher probability of MDRO infection. In a large secondary analysis of a worldwide CAP study, severe CAP had a much higher rate of Pseudomonas infection (28.6%) compared with S. pneumoniae (3.6%).[24]

Risk factors for MDRO in the community-acquired setting include hospitalizations greater than 5 days and antibiotic exposure within 90 days, immunocompromised status, structural lung diseases such as bronchiectasis and chronic obstructive pulmonary disease (COPD), and prior culture positivity or colonization by MDROs.[1] [7] [25] [26] [27] Distinct risk factors for MRSA also exist, and involve the presence or history of indwelling catheters, intravenous drug use, and human immunodeficiency virus (HIV) infection ([Table 1]).[28] [29]

Table 1 Risk factors for multidrug-resistant organisms

Setting	Risk factors
Community-acquired aspiration	• Hospitalizations greater than 5 days
	• Antibiotic exposure within 90 days
	• Immunocompromised status
	• Structural lung diseases
	• Prior culture positivity or colonization by drug-resistant organisms
	Methicillin-resistant Staphylococcus aureus-specific
	• Presence or history of indwelling catheters
	• Intravenous drug use
	• Human immunodeficiency virus infection
	• Prior respiratory cultures with MRSA
Hospital-acquired aspiration	ERS-specific
	• Mortality risk ≥15%
	• Local MDR organism prevalence ≥25%
	• Prior colonization with multidrug-resistant organism
	IDSA/ATS-specific
	• Acute respiratory distress syndrome
	• Acute renal replacement
	• MRSA prevalence is >10 to 20%
	• Multidrug-resistant gram-negative prevalence >10%
	Common risks
	• Septic shock
	• Prior antibiotic administration
	• Prior hospitalization ≥5 days

Abbreviations: ERS, European Respiratory Society; IDSA/ATS, Infectious Disease Society of America/American Thoracic Society; MDR, multidrug-resistant; MRSA, methicillin-resistant Staphylococcus aureus.

Hospital-Acquired Aspiration Pneumonia

Similar to CAAP, the predominant pathogens considered in HAAP are akin to the organisms responsible for the pathogenesis of hospital-acquired pneumonia (HAP). Early studies of HAAP demonstrated that the majority of cases involved aerobic bacteria (35% contained anaerobes), with Pseudomonas species, Proteus species, Escherichia coli, and Staphylococcus aureus as the predominant pathogens.[30] [31] With the use of protective specimen brushes in the early 1990s, HAAP etiology continued to recapitulate those seen in HAP: MRSA, H. influenzae, Klebsiella species, and Pseudomonas species.[20] Risk factors for MDRO are similar to those described in CAAP. These include recent extended hospitalization (≥5 days), and antibiotic administration within the past 90 days.[2] [3] Additionally, the local prevalence of MDROs, which can vary depending on the health care facility, plays a critical role in HAAP.[2] [3]

Anaerobic Organisms

The historical study of aspiration pneumonia, whether community- or hospital-acquired, initially implicated anaerobes as the primary pathogen. Several landmark papers published by Bartlett et al during the 1970s used percutaneous transtracheal aspiration to study a population of patients at risk of anaerobic infection, such as poor dentition, putrid sputum, and prolonged illness.[10] [30] [32] Notably, subjects were sampled several days or weeks into illness, resulting in cohort enrichment of necrotizing pneumonia, lung abscess, and empyema.[10] [30] [32] The most prominent species included Fusobacterium, Bacteroides, Prevotella, and Peptostreptococcus.[31] Pneumonia guidelines for decades stressed the coverage of anaerobes based on these data.

Starting in the 1990s, the use of protective specimen brushes during bronchoscopy obviated the need for invasive transtracheal cultures, and they did not demonstrate any significant anaerobic growth despite meticulous techniques.[20] [33] [34] When anaerobes were present, they were often co-cultured with aerobes.[20] [21] [33] Numerous subsequent studies have shown that a majority of organisms cultured in aspiration pneumonia were aerobic organisms such as S. pneumoniae, S. aureus, and H. influenzae.[20] [22] [24] [35] [36] [37] Additionally, even in the presence of lung abscesses and in-hospital aspirations, aerobic organisms continued to show predominance.[21] [33] [38] [39]

Treatment of Community-Acquired Aspiration Pneumonia

Antibiotic selection for CAAP should closely align with treatment protocols for CAP. While targeting common community pathogens, treatment decisions must also consider the risk of encountering MDROs, such as MRSA and P. aeruginosa.

Low-Risk Multidrug-Resistant Organism Community Acquired-Aspiration Pneumonia

For patients at low risk for MDRO infections, empiric therapy should consist of combination antibiotics. According to the Infectious Disease Society of America/American Thoracic Society's (IDSA/ATS) guidelines on CAP, and the European Respiratory Society (ERS) guidelines on severe CAP, this typically consists of a β-lactam antibiotic (ampicillin–sulbactam, cefotaxime, ceftriaxone, or ceftaroline) paired with either a macrolide (azithromycin or clarithromycin) or a fluoroquinolone (levofloxacin or moxifloxacin), with the ERS favoring the use of macrolides ([Fig. 1]).[1] [40]

Fig. 1 Therapeutic approach to aspiration pneumonia and chemical pneumonitis. For suspected aspiration pneumonia, antibiotic therapy depends on where the infection was acquired (community or hospital), and the risk of multidrug-resistant organisms. Antibiotics should be administered for those with abnormal chest X-rays. In individuals with clear chest X-rays, antibiotics are recommended for those who have severe illness (e.g., shock or intubation), otherwise, they can be withheld with a reassessment in 48 hours for mild cases. Routine anaerobic coverage is not needed unless the patient has poor dental health or complications such as pulmonary abscess or empyema. ATS, American Thoracic Society; ERS, European Respiratory Society; IDSA, Infectious Disease Society of America; MDR, multidrug-resistant; MRSA, methicillin-resistant Staphylococcus aureus.

Emerging and historical data support the benefits of combination therapy, particularly with macrolides. Observational studies suggest improved survival benefits when macrolides are added to β-lactams.[41] [42] [43] [44] [45] [46] For example, a European matched case-controlled study found an 80% reduction in intensive care unit (ICU) mortality in CAP patients receiving combination therapy compared with monotherapy.[47] In the recent Anti-inflammatory Action of Oral Clarithromycin in Community-acquired Pneumonia (ACCESS) randomized clinical trial (RCT), patients with CAP receiving clarithromycin alongside a β-lactam were evaluated against a β-lactam plus placebo. The primary outcome was early clinical response, defined as a reduction in respiratory symptom severity score by ≥50%, improvement in sequential organ failure assessment scores by at least 30%, or a favorable trend in procalcitonin (PCT) levels of ≥80% decrease from baseline or <0.25 ng/mL). The primary endpoint was met by 68% of patients in the clarithromycin group, compared with 38% in the placebo group. While mortality was not the primary focus, the study showed positive trends throughout the trial, and a subsequent analysis revealed a mortality benefit for the clarithromycin group at the end of treatment.[48]

High-Risk Multidrug-Resistant Organism Community Acquired-Aspiration Pneumonia

For suspected MDRO infections in CAAP, empiric treatment should include broad-spectrum antibiotics that cover MRSA and P. aeruginosa, in appropriate at-risk individuals. According to the IDSA/ATS CAP guidelines, if prior cultures point to MRSA, vancomycin or linezolid are recommended. For P. aeruginosa, options include piperacillin–tazobactam, cefepime, ceftazidime, aztreonam, or carbapenems like meropenem or imipenem.[1] These choices should be further guided by the local prevalence of MDROs and refined with susceptibility testing once cultures become available. In the absence of a prior positive culture, the guidelines recommend empiric coverage for Pseudomonas and/or MRSA based on the presence of risk factors for those with severe illness, but only if cultures are positive, in those with risk factors, but less severe CAP.

Anaerobic Coverage in Community Acquired-Aspiration Pneumonia

Both the IDSA/ATS guidelines for CAP and the ERS guidelines for severe CAP advise against routine anaerobic coverage for suspected aspiration pneumonia, except in cases involving complications such as lung abscess, empyema, or poor dentition.[1] [40] This approach is supported by evidence from observational studies and randomized controlled trials that have evaluated the impact of anaerobic coverage across various clinical outcomes, which include mortality, adverse events, and clinical response.

In terms of mortality, multiple studies have demonstrated no significant difference when comparing standard CAP treatments with and without anaerobic coverage. A multicenter, retrospective analysis comparing ceftriaxone with ampicillin–sulbactam found no difference in in-hospital mortality among patients with pneumonia who had one or more aspiration risk factors.[49] Similarly, a multicenter cohort study across 18 hospitals in Ontario, Canada, found no significant difference in in-hospital mortality between patients receiving limited anaerobic coverage (LAC) and those receiving extended anaerobic coverage (EAC). LAC was defined as monotherapy with ceftriaxone, cefotaxime, or levofloxacin, while EAC included additional antibiotics targeting anaerobic organisms, such as clindamycin and metronidazole (30.3 vs. 32.1%).[50]

The impact of anaerobic coverage on adverse events, particularly the incidence of Clostridium difficile infection, has also been evaluated. The Ontario study found that patients in the EAC group had a higher incidence of C. difficile infection (0.8–1.1%) compared with those in the LAC group (≤0.2%).[50] Additionally, a retrospective study of patients hospitalized with sepsis compared empiric administration of piperacillin–tazobactam with cefepime, finding that the piperacillin–tazobactam group not only had a higher risk of mortality but also experienced fewer ventilator-free, organ failure-free, and vasopressor-free days.[51] These findings highlight the potential harm of unnecessary anaerobic coverage and the importance of avoiding its indiscriminate use.

Furthermore, randomized studies have demonstrated no significant differences in clinical response when comparing a broad range of antibiotics with and without anaerobic coverage. These comparisons included carbapenems versus cephalosporins (e.g., cefepime), ampicillin–sulbactam versus ceftriaxone, piperacillin–tazobactam versus imipenem, and fluoroquinolones with and without metronidazole.[52] [53] [54]

Collectively, these findings suggest that standard CAP treatments likely provide adequate coverage for anaerobes when needed, and that anaerobes may not play a significant pathogenic role in most cases of aspiration pneumonia. Consequently, routine anaerobic coverage should be reserved for cases with clear indications, to avoid unnecessary risks and adverse outcomes.

Treatment of Hospital-Acquired Aspiration Pneumonia

The approach to antibiotic therapy for HAAP should align with the treatment strategies for HAP, particularly concerning the risk of MDROs. Key guidelines for treatment are provided by both the IDSA/ATS and the ERS, in collaboration with several other European and Latin American medical societies. For simplicity, the latter will be referred to as the ERS guidelines.

Empiric Antibiotic Therapy

Empiric antibiotic therapy for HAAP should be guided by the patient's risk factors for MDROs and local resistance patterns. Should coverage for MDROs be necessary, antibiotics targeting MRSA, P. aeruginosa, and other gram-negative bacilli must be considered.

For patients at lower risk of MDROs, monotherapy with a broad-spectrum β-lactam or a respiratory fluoroquinolone is suggested.[2] [3] The ERS guidelines specifically recommend ertapenem, ceftriaxone, cefotaxime, levofloxacin, or moxifloxacin for these cases. For high-risk patients, dual-antipseudomonal coverage with or without MRSA coverage is recommended.[2]

Both sets of guidelines identify several risk factors for MDROs. Similarities include septic shock, prior antibiotic use, and recent hospitalization (≥5 days).[2] [3] Differences include the IDSA/ATS guidelines' consideration of ARDS, the need for acute renal replacement therapy, structural lung diseases, and a local prevalence of >10% resistant gram-negative isolates, and >10 to 20% of MRSA isolates as additional risk factors.[3] The ERS guidelines consider patients with ≥15% mortality risk, ≥25% local prevalence of resistant organisms (either gram-negative or MRSA), and prior colonization with resistant organisms as high risk.[2]

Treatment for Methicillin-resistant Staphylococcus aureus

Vancomycin and linezolid are the primary agents recommended for treating MRSA. The ERS guidelines favor linezolid over vancomycin due to its higher treatment success rates and lower nephrotoxicity.[2] Specifically, a study involving 1,184 patients with MRSA pneumonia found no significant differences in mortality between linezolid and vancomycin, but the linezolid group had a higher treatment success rate (57.6 vs. 46.6%) and lower nephrotoxicity (8.4 vs. 18.2%).[55]

Treatment for Pseudomonas aeruginosa and Multidrug-Resistant Gram-Negative

For patients at high risk for MDRO gram-negative, dual-antibiotic therapy is recommended. This approach offers significant benefits, including both improved mortality and treatment success, particularly in patients with septic shock.[56] [57] [58] [59] [60] Combination therapy typically involves two antibiotics: a broad-spectrum β-lactam antibiotic as the foundation, and a second agent chosen from either aminoglycosides or antipseudomonal fluoroquinolones. While the IDSA/ATS guidelines favor fluoroquinolones due to concerns about potential nephrotoxicity, ototoxicity, and limited lung penetration associated with aminoglycosides, the ERS guidelines give preference to these agents (aminoglycosides like gentamicin, amikacin, or tobramycin).[2] [3] The advantage of aminoglycosides may be related to the higher rates of gram-negative resistance among fluoroquinolones, in most ICUs around the world.

Optimizing Therapy: Treatment Duration and Deescalation

Treatment Duration in Community-Acquired Aspiration Pneumonia

The IDSA/ATS guidelines recommend a 5- to 7-day antibiotic course for most cases of CAP and CAAP.[1] However, this duration may be extended for suspected MDRO infections or based on individual patient factors. Factors influencing extension include the patient's clinical course and the presence of complications like empyema or endocarditis.

Treatment Duration for Hospital-Acquired Aspiration Pneumonia

Compelling data also support a shorter duration of antibiotic therapy for patients with HAAP. Both IDSA/ATS and the ERS guidelines recommend a 7-day regimen.[2] This is backed by robust evidence, including systematic reviews and meta-analyses of RCTs showing no significant difference in mortality, ICU stay length, or mechanical ventilation duration when comparing 7 to 8 days to longer courses (10–15 days).[61] [62] [63] [64]

Antibiotic Deescalation

The growing threat of antimicrobial resistance makes antibiotic stewardship, particularly de-escalation strategies, critically important. While tools for guiding de-escalation have been limited, recent data offer a promising option in the utilization of PCT. Three trials involving critically ill patients suggest serial PCT measurements, showing a decrease (≤0.5 μg/L or an 80% reduction from baseline), can safely guide antibiotic discontinuation when combined with clinical judgment.[65] [66] [67] All three trials reported a shorter duration with PCT guidance. While some trials showed reduced mortality, all showed no increase in MDRO colonization. This suggests that PCT-guided antibiotic management could potentially shorten treatment duration while improving outcomes, including fewer antibiotic-associated adverse events.

Corticosteroids as an Adjunctive Therapy

The evidence for a mortality benefit with corticosteroids has been mixed. While some large trials showed positive results, others did not.[68] [69] [70] Due to inconsistencies in the data, professional guidelines have not recommended their widespread use, with the exception of patients in septic shock.[1] [2] [3]

Recently, another multicenter trial called the Community-Acquired Pneumonia: Evaluation of Corticosteroids (CAPE COD) rekindled interest in corticosteroids for severe CAP. This study demonstrated that administering hydrocortisone to patients with severe CAP improved their 28-day mortality compared with a placebo.[71] A high proportion of patients in the trial were on high-flow nasal cannulas for oxygen support, with only a small percentage requiring mechanical ventilation. The use of hydrocortisone was also associated with a reduced need for intubation and less frequent use of vasopressors.

Subgroup analyses within the CAPE COD trial suggested that patients with higher levels of inflammatory markers (most notably C-reactive protein ≥15 mg/dL) might benefit most from corticosteroids. This is consistent with previous research that demonstrated reduced treatment failure rate in patients with severe CAP and indicators of high levels of inflammation, who were treated with corticosteroids.[70] Overall, this suggests that a targeted approach, focusing on patients with a hyperinflammatory profile, might be most effective for corticosteroid therapy.

The growing body of evidence, particularly from the CAPE COD trial, warrants further investigation into the potential benefits of corticosteroids for specific patients. However, for now, a tailored approach based on individual patient characteristics seems more appropriate than routine use. Data on patients with aspiration pneumonia are still needed to address the role of corticosteroid therapy in this specific population.

Treatment of Chemical Pneumonitis

The treatment of chemical pneumonitis should focus primarily on supportive care, targeting airway injury and preventing complications. Key interventions include supplemental oxygen, management of bronchospasm and pulmonary edema, bronchoscopy for airway clearance, and positive pressure ventilation in severe cases. Although empiric corticosteroid therapy is not currently recommended for chemical pneumonitis, in cases of ARDS, early corticosteroid use within 7 days of mechanical ventilation has shown a mortality benefit.[72]

Regarding antibiotic therapy, the risk of secondary bacterial pneumonia certainly exists, which has led to interest in empiric antimicrobial treatment. However, the evidence supporting this practice is limited. In a retrospective study of 200 patients with acute aspiration pneumonitis, early antibiotic use (38%) was compared with supportive care alone (62%). The study found no significant differences in critical care transfers or in-hospital mortality between the two groups.[73]

In mild-to-moderate cases, antibiotics can be withheld for the first 48 hours, even in the presence of radiographic infiltrates, while closely monitoring the patient's clinical status. After this period, a reassessment should guide subsequent treatment decisions. In severe cases, empiric antibiotics may be started even if chest radiographs are clear, with bronchoscopy performed as needed to obtain cultures and refine management. The decision to continue antibiotics beyond 48 to 72 hours should be based on the patient's clinical course and response to treatment.[4]

Conclusion

The treatment of aspiration pneumonia requires a comprehensive and tailored approach that integrates current microbiological insights and individual patient risk profiles for MDROs, including the location and timing of aspiration, as well as patient-specific risks. Empiric antibiotic choices should reflect these complexities, with options ranging from monotherapy in low-risk cases to combination and broad-spectrum therapies for those at higher risk. By carefully balancing the need for broad-spectrum coverage with the principles of antibiotic stewardship, we can maximize treatment efficacy, minimize the risk of resistance and adverse outcomes, and promote responsible antibiotic use.

Conflict of Interest

None declared.

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Publikationsverlauf

Artikel online veröffentlicht:
25. Oktober 2024