CONTENTS
- Streptococcus pneumoniae (pneumococcus)
- Streptococcus pyogenes (Group A strep)
- Staphylococcus aureus (MSSA & MRSA)
- Haemophilus influenzae
- Moraxella catarrhalis
- Pseudomonas aeruginosa
- Klebsiella pneumoniae
- Other related topics:
- Questions & discussion
abbreviations used in the pulmonary section: 3
- ABPA: Allergic bronchopulmonary aspergillosis 📖
- AE-ILD: Acute exacerbation of ILD 📖
- AEP: Acute eosinophilic pneumonia 📖
- AFB: Acid Fast Bacilli
- AIP: Acute interstitial pneumonia (Hamman-Rich syndrome) 📖
- ANA: Antinuclear antibody 📖
- ANCA: Antineutrophil cytoplasmic antibodies 📖
- ARDS: Acute respiratory distress syndrome 📖
- ASS: Antisynthetase Syndrome 📖
- BAL: Bronchoalveolar lavage 📖
- BiPAP: Bilevel positive airway pressure 📖
- CEP: Chronic eosinophilic pneumonia 📖
- CF: Cystic fibrosis 📖
- COP: Cryptogenic organizing pneumonia 📖
- CPAP: Continuous positive airway pressure 📖
- CPFE: Combined pulmonary fibrosis and emphysema 📖
- CTD-ILD: Connective tissue disease associated interstitial lung disease 📖
- CTEPH: Chronic thromboembolic pulmonary hypertension 📖
- DAD: Diffuse alveolar damage 📖
- DAH: Diffuse alveolar hemorrhage 📖
- DIP: Desquamative interstitial pneumonia 📖
- DLCO: Diffusing capacity for carbon monoxide 📖
- DRESS: Drug reaction with eosinophilia and systemic symptoms 📖
- EGPA: Eosinophilic granulomatosis with polyangiitis 📖
- FEV1: Forced expiratory volume in 1 second 📖
- FVC: Forced vital capacity 📖
- GGO: Ground glass opacity 📖
- GLILD: Granulomatous and lymphocytic interstitial lung disease 📖
- HFNC: High flow nasal cannula 📖
- HP: Hypersensitivity pneumonitis 📖
- IPAF: Interstitial pneumonia with autoimmune features 📖
- IPF: Idiopathic pulmonary fibrosis 📖
- IVIG: Intravenous immunoglobulin 📖
- LAM: Lymphangioleiomyomatosis 📖
- LIP: Lymphocytic interstitial pneumonia 📖
- MAC: Mycobacterium Avium complex 📖
- MCTD: Mixed connective tissue disease 📖
- NIV: Noninvasive ventilation (including CPAP or BiPAP) 📖
- NSIP: Nonspecific interstitial pneumonia 📖
- NTM: Non-tuberculous mycobacteria 📖
- OP: Organizing pneumonia 📖
- PAP: Pulmonary alveolar proteinosis 📖
- PE: Pulmonary embolism 📖
- PFT: Pulmonary function test 📖
- PLCH: Pulmonary Langerhans Cell Histiocytosis 📖
- PPFE: Pleuroparenchymal fibroelastosis 📖
- PPF: Progressive pulmonary fibrosis 📖
- PVOD/PCH Pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis 📖
- RB-ILD: Respiratory bronchiolitis-associated interstitial lung disease 📖
- RP-ILD: Rapidly progressive interstitial lung disease 📖
- TNF: tumor necrosis factor
- UIP: Usual Interstitial Pneumonia 📖
epidemiology
- Pneumococcal pneumonia is of the most common causes of pneumonia, including severe pneumonia.
- Pneumococcus is spread via droplets in a person-to-person fashion.
- Outbreaks may occur among adults living in crowded conditions (e.g., jail, military barracks).
- Infections are most common in the winter and early spring. (Murray 2022)
- Different serotypes of pneumococcus may have varying tendencies to cause invasive disease or empyema.
- Risk factors for pneumococcal pneumonia include: (Fishman 2023, 27960205)
- Smoking.
- Preceding influenza or RSV infection.
- Older age.
- Chronic conditions:
- Chronic pulmonary disease (e.g., COPD, asthma).
- Chronic liver disease.
- Chronic renal failure.
- Diabetes.
- Alcoholism.
- Immune dysfunction:
- Asplenia, sickle cell disease, celiac disease.
- HIV: Pneumococcus is a leading cause of pneumonia among people living with HIV (even among patients with normal CD4 counts). Patients may be at increased risk of recurrent disease.
- B-cell defects, multiple myeloma.
- Immunosuppressive medications (chemotherapy, antimetabolites, steroid).
- Solid organ transplantation
clinical presentation
- Classic presentation:
- Abrupt onset of severe chills/rigors, followed by fever.
- Severe pleuritic chest pain.
- Cough productive of blood-tinged, tenacious “rusty” sputum.
- (Nausea/vomiting or diarrhea can be prominent.)
- Alternative/unusual presentations:
- Elderly patients: fatigue or altered mental status.
- Asplenic patients: shock and hemorrhagic skin lesions due to DIC.
- Right lower lobe pneumonia may cause hyperbilirubinemia, masquerading as acute cholecystitis.
- Clinical course:
- Empyema or parapneumonic effusion is common.
- 💡 Consider repeating POCUS to evaluate for effusion every few days, since these effusions may pop up when you're least expecting them to.
radiology
- Pneumococcus generally causes a lobar pneumonia:
- This often causes relatively large, homogeneous consolidation with air bronchograms.
- Consolidations may be unifocal or multifocal.
- An isolated round area of consolidation may occur (“round pneumonia”).
- Given how common pneumococcal pneumonia is, unusual radiographic patterns will also be encountered (e.g., patchy bronchopneumonia can occur). (Walker 2019)
- Pleural effusion is common (affecting about a third of critically ill patients).
- CT scan may show some lymphadenopathy in about half of cases. (Walker 2019)
- Cavitation is rare (if seen, this might suggest a superimposed co-infection or alternative diagnosis).
general laboratory tests
- Neutropenia is occasionally seen, especially among patients with a history of alcoholism. The association of neutropenia, alcoholism, and bacteremic pneumococcal pneumonia has historically been labeled as “ALPS” (alcoholic leukopenic pneumococcal sepsis). Therapy for ALPS includes standard treatments for pneumonia as well as supportive care for alcoholism (e.g., folate, thiamine, treatment of alcohol withdrawal). There is no need for exogenous granulocyte stimulating factors, since endogenous cytokine levels are high and the leukocyte levels will rebound naturally over time.
specific laboratory studies
- Sputum Gram stain may show slightly elongated (“lancet-shaped”) gram-positive cocci in pairs or chains. However, sputum culture is often negative (since pneumococcal bacteria are fastidious and difficult to grow).
- Blood culture is positive in ~25% of patients.
- Pneumococcal urinary antigen has a sensitivity of ~75% and specificity of ~95%. False-positive results may occur if the patient had a pneumococcal pneumonia in the past three months.
treatment
antibiotics
- Discussed in the antibiotics file here: 📖
steroid
- Based on evidence regarding the use of steroid in pneumococcal meningitis, steroid is be expected to be especially beneficial for patients with pneumococcal pneumonia.
- A general discussion of the role of steroid in bacterial pneumonia is here: 📖
epidemiology
- Group A Streptococcus is an uncommon cause of pneumonia (<5% of bacterial pneumonia)
- Outbreaks may occur (e.g., nursing homes, military barracks).
- Infection may be more common in the winter and spring. (27738486)
- Risk factors:
- Influenza is the most important risk factor.
- Older age.
- Alcoholism, diabetes, cancer, or COPD.
clinical presentation
- Initial pneumonia may be marked by a very high incidence of pleuritic chest pain.
- Exudative streptococcal pharyngitis may occasionally be seen.
- Numerous complications occur, with an overall high rate of mortality.
- Toxic shock syndrome (25-33% of patients). (27027618)
- Empyema (~20%). About half of patients have pleural effusion – and these are very frequently infected.
- Necrotizing pneumonia with abscess formation and cavitation.
- Less common complications include pericarditis, pneumothorax, and mediastinitis. (Murray 2022)
radiology
- Necrotizing pneumonia with cavity formation may occur.
- Pleural effusion with empyema may occur.
laboratory tests
- Bacteremia is very common (~75%). (27738486)
- Streptococci may colonize the oropharynx, so growth on a sputum culture isn't necessarily diagnostic of pneumonia.
treatment
Aggressive therapy is warranted, since the mortality of group A streptococcal pneumonia is quite high (~20-50%). (27738486) Infection can be rapidly fatal, even in previously healthy individuals – likely driven by toxic shock syndrome. (27027618)
antibiotics
- Discussed in the antibiotics section here: 📖
steroid
- Given the high rate of systemic inflammation, adjunctive steroid may be advisable. More on the role of steroid in community-acquired pneumonia here: 📖
management of toxic shock syndrome
- About a third of patients may develop toxic shock syndrome.
- For patients with multiple organ failures, consider IVIG.
- More on the diagnosis and management of streptococcal toxic shock here: 📖
pleural effusion management
- Given the very high rate of empyema, pleural effusions should be treated aggressively. It might be reasonable to insert a pigtail drain for any moderate or large effusion.
basics
- Staphylococcus aureus may either be methicillin sensitive (MSSA) or methicillin resistant (MRSA). There are roughly two different types of MRSA, which may tend to behave in different ways:
- HA-MRSA (hospital-acquired methicillin-resistant Staphylococcus aureus).
- This often represents a form of nosocomial Staphylococcus aureus with broad drug resistance (e.g., resistant to erythromycin, clindamycin, aminoglycosides, and fluoroquinolones).
- Clinically, HA-MRSA behaves similarly to MSSA.
- CA-MRSA (community-acquired methicillin-resistant Staphylococcus aureus).
- This is a strain of Staphylococcus which has achieved methicillin resistance while simultaneously becoming more virulent. These bacteria generally harbor Panton-Valentine leukocidin genes that increase virulence by causing tissue destruction (with a tendency to cause very aggressive, necrotizing pneumonia; often in young adults).
- Unlike HA-MRSA, CA-MRSA is often susceptible to numerous non-beta-lactam antibiotics (e.g., clindamycin, aminoglycosides, trimethoprim-sulfamethoxazole, fluoroquinolones, doxycycline). (32521547)
- Staphylococcus aureus often causes tricuspid endocarditis, which leads to septic pulmonary emboli. The presentation and radiology of septic pulmonary emboli is distinct from that of primary pneumonia. Septic pulmonary emboli are discussed here: 📖
epidemiology
- Risk factors for Staphylococcus aureus pneumonia:
- Stronger risk factors:
- Diabetes.
- Hemodialysis.
- Prior influenza or RSV infection.
- Other risk factors:
- Immunocompromise.
- HIV.
- COPD, other chronic heart or lung diseases.
- Stronger risk factors:
- Risk factors for MRSA in general:
- Stronger risk factors:
- Prior MRSA infection.
- Recurrent skin infections.
- Hospitalization with parenteral antibiotic therapy within three months.
- Other risk factors:
- Chronic hemodialysis. (32521547)
- Residence in a nursing home.
- Stronger risk factors:
- Risk factors for CA-MRSA (community-acquired MRSA):
- Soldiers, prisoners, and athletes (especially contact sports).
- IV drug use.
- Household contact with CA-MRSA.
- Men who have sex with men.
- Recurrent skin infections.
- Recurrent MRSA infection or colonization.
clinical presentation
- Patients are generally acutely ill.
- Purulent sputum production is the rule.
- There is a syndrome of necrotizing community-acquired pneumonia in young patients (usually due to CA-MRSA strains harboring Panton-Valentine leukocidin genes):
- (#1) Prodrome may include a flu-like illness. Alternatively, skin or soft-tissue infection (e.g., abscesses) may be present in ~20% of patients.
- (#2) Fulminant respiratory failure subsequently occurs, often with shock. Leukopenia commonly occurs. (Murray 2022) Radiology may show early cavitation, lung necrosis, rapidly increasing infiltrates, and/or a rapidly increasing pleural effusion. Massive hemoptysis may occur, which is unlike most other community-acquired pneumonias. (32521547).
- Erythroderma may occur, as a component of staphylococcal toxic shock syndrome. (32521547).
radiology
- Primary process is often a bronchopneumonia:
- Findings may include ground-glass opacities, patchy consolidation, bronchial wall thickening, and/or centrilobular nodules. (Rosado-de-Christenson 2022)
- Inflammatory exudate may fill airways, leading to segmental collapse.
- Air bronchograms are rarely seen. (Walker 2019)
- Necrotizing pneumonia often occurs:
- Abscess formation and cavitation are relatively common.
- Necrosis increases the risk of bronchopleural fistula (pneumothorax).
- Pneumatoceles 📖 may be seen, which can mimic abscess formation.
- Empyema is relatively common:
- Pleural effusion occurs in ~40% of patients, with half being empyema. (Walker 2019)
laboratory tests
- Neutropenia may occur. (32521547)
- Nares PCR may be useful to largely exclude Staphylococcus aureus if negative, but a positive result may simply reflect colonization.
- Staphylococcus aureus is generally easy to recover from respiratory secretions (even following several doses of antibiotic). The presence of intracellular organisms may further support the presence of an invasive pneumonia.
treatment
basics
- H. influenzae is a small, facultatively anaerobic, pleomorphic gram-negative coccobacillus.
- Encapsulated vs. unencapsulated H. flu:
- Encapsulated strains are typed (serotypes a through f). Haemophilus influenzae B (HIB) used to be a dominant form, but this has decreased due to vaccination. Encapsulation helps bacteria to evade immune clearance, potentially leading to bacteremia.
- Unencapsulated strains are non-typeable, less virulent, and cannot be prevented by current vaccines. Currently, ~80% of cases of H. influenzae in adults are non-typeable. Non-typeable H. influenzae rarely cause bacteremia. (Brown 2021)
- H. influenzae causes COPD exacerbation more often than it causes pneumonia, so isolation from the respiratory tract doesn't necessarily prove an invasive pneumonia.
epidemiology
- Haemophilus influenzae may cause ~5% of community-acquired pneumonia.
- Risk factors include older age, medical comorbidity, and smoking.
clinical presentation
- Clinically, this is similar to other bacterial pneumonias.
- H. influenzae tends to have a lower morbidity/mortality than other bacterial pneumonias.
radiographic pattern is variable
- H. influenzae may cause lobar or segmental consolidation, simulating pneumococcal pneumonia. However, patchy bronchopneumonia may also be seen.
- CT scan may show a tree-in-bud pattern, indicating infectious bronchiolitis.
- (It's likely that encapsulated versus non-encapsulated species produce different patterns. By combining both types together, we lose the ability to discern any radiographic pattern.)
laboratory tests
- Gram stain is often negative, since the organisms are small and easily overlooked.
- Sputum culture is positive in about half of patients, but this is confusing since H. influenzae can cause asymptomatic colonization among patients with COPD. (Murray 2022)
treatment
- Antibiotics discussed here: 📖
basics
- Moraxella catarrhalis is an unencapsulated, gram-negative diplococcus.
- This is a low-virulence organisms that is clinically similar to non-typeable Haemophilus influenzae.
- The most common clinical manifestation is COPD exacerbation, but pneumonia may also occur.
epidemiology
- Pneumonia seldom occurs in previously healthy people. (Walker 2019; 33172398)
- The most common risk factors:
- Elderly.
- Underlying lung disease (COPD, asthma, bronchiectasis).
- Other risk factors:
- Cardiopulmonary comorbidity.
- Alcoholism, malnutrition.
- Malignancy with neutropenia.
- Infection may be more common in the winter. (33172398)
clinical presentation
- Often causes a mild pneumonia.
- Cough is productive of purulent sputum.
- Pleuritic chest pain or high fever are uncommon. (Murray 2022)
radiology
- May cause patchy bronchopneumonia, often predominantly in the lower lobes and generally (90%) bilaterally. (33172398)
- Pleural effusion is uncommon.
- (Okada et al. includes examples of CT radiology: 📄 )
laboratory tests
- Moraxella catarrhalis is frequently part of the normal upper respiratory tract flora, so growth in sputum doesn't necessarily indicate invasive disease. (Murray 2022)
- High-quality sputum on Gram stain may support the diagnosis of pneumonia.
- Intracellular gram-negative diplococci also support a true infection. (Murray 2022)
treatment
- Most species produce a beta-lactamase, rendering amoxicillin or ampicillin ineffective.
- Treatment options include:
- Third generation cephalosporin.
- Beta-lactam/beta-lactamase combination (e.g., ampicillin-sulbactam).
- Fluoroquinolones.
- Doxycycline.
- Trimethoprim-sulfamethoxazole.
epidemiology
- Pseudomonas is a rare cause of community-acquired pneumonia (only 1-2%). However, pseudomonas is a very common cause of ventilator-associated pneumonia (likely related to breeching of the upper airway defenses by the endotracheal tube).
- Risk factors for Pseudomonas in patients with CAP (community-acquired pneumonia):
- (1) Structural lung disease:
- Bronchiectasis (especially cystic fibrosis).
- Prior tracheostomy.
- Severe COPD (especially with FEV1 <30% predicted, or recurrent exacerbations requiring steroid and antibiotic use). (32561442)
- (2) Immunosuppression:
- Neutropenia/hematologic malignancy.
- HIV with CD4 count <50/uL.
- (3) Prior colonization or infection with Pseudomonas.
- (1) Structural lung disease:
- 💡If a patient with no apparent risk factors develops a Pseudomonas pneumonia, consider evaluation for HIV or structural lung disease (e.g., bronchiectasis).
clinical presentation
- The initial presentation is generally similar to that of other pneumonias.
- If initial empiric therapy doesn't cover Pseudomonas, the pneumonia will fail to respond to therapy (e.g., with worsening infiltrates and often radiographic cavitation).
- Among patients with bacteremia, physical examination may show ecthyma gangrenosum.
radiology
- Bronchopneumonia is usually the primary radiographic form of pneumonia, e.g.:
- Peribronchovascular ground-glass opacities.
- Centrilobular nodules (including tree-in-bud nodules).
- Bronchial wall thickening.
- Eventually, lobular consolidations may become confluent leading to large areas of consolidation (similar to a primarily lobar pneumonia).
- Necrosis with cavity formation is common, especially among immunocompromised hosts. (Rosado-de-Christenson 2022)
- Pleural effusion is common.
laboratory tests
- Pseudomonas is a common colonizer of the oropharynx in debilitated or hospitalized patients, so simply culturing Pseudomonas from sputum doesn't prove invasive pneumonia.
- A positive culture for Pseudomonas is much more convincing it if is paired with a high-quality Gram stain (>25 leukocytes and <10 squamous cells per low-power field) showing a predominance of gram-negative bacilli.
- 💡 The sputum Gram stain may help judge the accuracy of the culture result (e.g., whether the sputum truly represents material from the lower respiratory tract, or saliva).
treatment
- Antibiotics discussed here: 📖
epidemiology
- Community-acquired pneumonia:
- Rare cause of community-acquired pneumonia (~3-5%).
- Risk factors include:
- Alcoholism.
- Diabetes.
- Chronic lung disease (e.g., COPD).
- Cigarette smoking.
- Nosocomial pneumonia: Klebsiella pneumonia is a common cause of nosocomial pneumonia (~10-15%).
clinical presentation
- Usual presentation:
- Clinical presentation is generally similar to that of other pneumonias.
- Traditionally, Klebsiella was associated with “currant jelly” sputum.
- Rarely, a chronic necrotizing pneumonia may develop, which can mimic tuberculosis.
- Pneumonia is often associated with bacteremia.
radiology
- Lobar consolidation is usually seen:
- Frequently involves the right upper lobe.
- Traditionally, Klebsiella has been associated with a bulging fissure sign (exuberant inflammation causes an increase in volume of the affected lobe). However, the bulging fissure sign may be associated with a variety of pathogens, as discussed further here: 📖
- Effusion (~65%) and empyema frequently occur. Effusion may be contralateral to parenchymal involvement.
- Aggressive lung necrosis may occur: Klebsiella may cause rapid necrosis, with cavitation and abscess formation. Before cavitation occurs, necrotic areas may be noted on CT scan as areas of the lung that fail to normally opacify with contrast.
- Various outcomes of lung necrosis may include: (Rosado-de-Christenson 2022)
- (1) Lung abscess.
- (2) Pulmonary gangrene may occur due to vascular and bronchial obstruction, which results in massive necrosis of the lung.
- (3) Chronic pneumonia may occur. Occasionally the infection may fail to resolve, progressing instead into a chronic phase. Radiological features may include cavitation or low-attenuation necrotic areas within pulmonary consolidation. (Walker 2019) Overall this may mimic a mycobacterial or fungal pneumonia.
treatment
- See the antibiotics file: 📖
basics
- Rhodococcus is an aerobic intracellular gram-positive coccobacillus that is partially acid-fast. It shares many similarities with Nocardia and Mycobacterium species.
epidemiology
- Rhodococcus is primarily an opportunistic infection affecting patients with impaired cell-mediated immunity, including the conditions listed below. However, apparently immunocompetent people can be infected (perhaps in relationship to intense exposure). (29777923)
- HIV (especially with CD4 count <100-200/uL).
- Iatrogenic immunosuppression:
- Cancer chemotherapy.
- Steroid use.
- Anti-TNF therapy.
- Organ transplantation.
- Anti-CD52 immunotherapy (alemtuzumab).
- Rhodococcus is a frequent pathogen in horses, cattle, and pigs. Acquisition may be associated with livestock, contaminated soil, or livestock waste. However, patients often acquire Rhodococcus without obvious environmental contact. (Fishman 2023)
clinical presentation
- May cause pulmonary or disseminated infection (with associated neurologic and skin lesions).
- Presentation is often indolent (initially with fever, nonproductive cough, and mild dyspnea). (Fishman 2023)
- Rhodococcus may cause IRIS (immune reconstitution inflammatory syndrome) following initiation of therapy for HIV.
radiology
- The most common radiologic finding is multiple, large areas of dense consolidation.
- Cavitation may occur in about half of cases.
- Cavities are usually thick-walled, with air-fluid levels (figure below).
- Rupture into the pleura may lead to pneumothorax.
- Any lobe may be affected.
- Pleural effusion is common (including empyema).
- Infection may spread to involve the chest wall, or mediastinum (causing mediastinitis).

laboratory tests
- Rhodococcus is a pleomorphic, gram-positive bacillus that grows well on most media. It is slightly acid-fast (similar to Nocardia).
- Rhodococcus may be readily cultured from a variety of sources (e.g., sputum, blood, bronchoalveolar lavage, and/or pleural fluid.
- If Rhodococcus is isolated from the sputum, this indicates active infection.
- ⚠️ The laboratory should be notified of a suspicion for Rhodococcus, because colonies may be misinterpreted as representing normal flora (i.e., “diphtheroid” or “Coryneform” contaminants). (Fishman 2023)
treatment
- Given the rarity of this infection, optimal therapy is poorly defined.
- Combination antibiotic therapy is often needed for ~2-6 months (similar to nocardiosis or tuberculosis).
- Immunosuppression should be reduced, if possible.
basics
organism properties
- Gram-negative coccobacillus.
- Short, broad gram-negative rods in rapid growth phase.
- Coccobacillary shape in stationary phase.
- Strictly aerobic, catalase-positive, oxidase-negative, indole-negative, doesn't ferment glucose or reduce nitrate.
epidemiology
- Common source of nosocomial infection (in decreasing incidence):
- Ventilator associated pneumonia.
- Central line-associated bloodstream infection.
- Catheter-associated urinary tract infection.
- Surgical site infection.
- Risk factors:
- Debilitation.
- Breeching normal lines of defense (surgery, central line, tracheostomy, intubation).
- Exposure to third-generation cephalosporins, fluoroquinolones, or carbapenems.
- ICU stay.
- Community-acquired acinetobacter is rare in the United States.
- >90% of clinical isolates are Acinetobacter baumannii.
common clinical presentations
- Ventilator-associated pneumonia.
- Colonization usually precedes pneumonia, so these must be differentiated. Pay attention to tracheal aspirate gram stain, and the presence of other organisms (e.g., heavy growth of MRSA plus sparse growth of acinetobacter probably isn't an acinetobacter pneumonia).
- Acinetobacter VAP usually arises relatively late in the patient's ICU stay.
- Bloodstream infection:
- Acinetobacter may account for ~2% of nosocomial bloodstream infection (but this varies with geography).
- The most common sources of bacteremia are vascular catheters or pneumonia.
- Skin/wound infections.
- Urinary tract infection (nearly always associated with an indwelling catheter).
treatment part #1/3: treatment of acinetobacter with sensitivity pending
- This is challenging. Treatment may depend on local antibiograms (if available), the patient's prior sensitivities, the site and seriousness of the infection, and which agents are available locally.
- If there is a high incidence of CRAB, initiating a two-drug regimen designed to cover CRAB makes sense (with subsequent de-escalation if sensitivities reveal a more easily treated organism). Treatment strategies for CRAB are discussed below (see #3/3).
- If there is a low incidence of CRAB, then imipenem or meropenem may be reasonable choices. Depending on local susceptibility patterns, combination therapy may also be considered. (Warrier 2023)
treatment part #2/3: treatment of carbapenem-sensitive acinetobacter
defining resistance
- Multidrug-resistant: Resistant to at least one agent in three or more antibiotic groups (e.g., G3-G4 cephalosporins, fluoroquinolones, aminoglycosides, carbapenems, piperacillin-tazobactam, ampicillin-sulbactam).
- Extensively drug-resistant: Resistant to at least one agent in all but two or fewer antibiotic classes.
- Carbapenem-resistant: Resistant to at least one antipseudomonal carbapenem (i.e., imipenem or meropenem).
- Treatment of this is described in the section below.
front-line antibiotics (preferred for susceptible isolates)
- Beta-lactams, e.g.:
- Ceftazidime.
- Cefepime.
- Ampicillin/sulbactam (sulbactam is active component) – excellent track record, but some suggest reserving its use for resistant strains of Acinetobacter.
- Piperacillin-tazobactam.
- Carbapenems:
- Strains may be sensitive to either imipenem or meropenem, so be careful when interpreting sensitivity data.
- Fluoroquinolones.
- Aminoglycosides (only front-line for urinary tract infection):
- Amikacin is most often effective.
monotherapy vs. dual therapy
- Mild infections (e.g., UTI, skin/soft tissue infection with source control).
- Monotherapy is preferred.
- Urinary tract infections can be treated with aminoglycosides or TMP/SMX (if susceptible).
- Moderate to severe infections: Combination therapy is often recommended, but it remains unknown if this is truly required. Combination therapy might theoretically avoid treatment-emergent resistance and issues surrounding heteroresistance (some clones are resistant to an antibiotic, but this isn't detected by the laboratory). (37930071)
- For example: {beta-lactam or carbapenem} plus {aminoglycoside or fluoroquinolone}.
- If only susceptible to one front-line agent, a second-line agent may be added (e.g., a tetracycline or polymyxin as listed below). However, data suggests avoiding the combination of polymyxins with carbapenems.
- Once clinical improvement occurs, consider transition to monotherapy.
treatment part #3/3: CRAB (carbapenem-resistant acinetobacter baumannii)
general considerations in treatment of CRAB
- Definition of CRAB:
- CRAB refers to an acinetobacter isolate that is resistant to at least one antipseudomonal carbapenem (e.g., imipenem and/or meropenem).
- The term CRAB is generally utilized to refer to isolates within the entire Acinetobacter calcoaceticus baumannii complex (which includes A. Baumannii, A. calcoaceticus, A. pittii, and A. nosocomialis).
- Treatment delays are generally inevitable.
preferred: sulbactam-durlobactam plus a carbapenem (imipenem/meropenem)
- This is the preferred regimen for hospitals with access to sulbactam-durlobactam.
- Durlobactam is a beta-lactamase inhibitor with activity against class A (e.g., TEM-1), Class C (e.g., ADC), and class D beta-lactamases (E.g., OXA-24/40, OXA-23). It misses class B metallo-beta-lactamases (e.g., NDM) but these are currently uncommon.
- Sulbactam preferentially binds to PBP1 and PBP3 (penicillin binding proteins), whereas imipenem preferentially binds to PBP2. (IDSA 12/23 guideline)
- If there is resistance to sulbactam-durlobactam (e.g., MICs ≧16/4 ug/mL), then sulbactam-based therapy is unlikely to work. (IDSA 12/23 guideline)
alternative: high-dose ampicillin-sulbactam combination therapy
- High-dose ampicillin-sulbactam (9 grams/day sulbactam).
- 9 grams/day may be effective for sulbactam MICs up to 16-32 ug/mL (which are technically resistant).
- Even if CRAB is susceptible to ampicillin-sulbactam, IDSA guidelines still recommended high dose ampicillin-sulbactam (9 grams/day sulbactam).
- -PLUS ONE ADDITIONAL AGENT–
- Polymyxin B:
- Polymyxin B is generally preferred over colistin due to a more favorable PK profile, but it has poor pulmonary or urinary penetration. (IDSA 12/23)
- If the polymyxin MIC is >2 ug/ml, polymyxins are probably ineffective. (IDSA 12/23)
- Colistin: Favored for CRAB UTIs due to conversion to its active form in the urinary tract. (IDSA 12/23)
- Minocycline or tigecycline:
- The minocycline breakpoint is technically ≦4 ug/mL, but minocycline dosed at 200 mg iv q12 hours won't predictably cover organisms with an MIC >1 ug/mL. Consequently, minocycline may fail to work for organisms which are labeled as being “sensitive.” Tigecycline has no defined breakpoint. (IDSA 12/23)
- Tigecycline should be dosed in an adequate fashion to work (at least 200 mg IV load followed by 100 mg q12hr).
- Tetracyclines aren't desirable for bacteremia or urinary tract infections (low blood, urine levels).
- Cefiderocol.
- CREDIBLE-CR trial found increased mortality rates when cefiderocol was used. (33058795)
- This isn't a preferred treatment. It should be limited to infections refractory to other antibiotics.
pathophysiology: mechanism of CRAB formation
- CRAB is mostly caused by carbapenemases of class B (metallo-beta-lactamases) and D (oxacillin uses). OXA carbapenemases (e.g., OXA-23, OXA-24/40) may be the most common, causing resistance to beta-lactams (including carbapenems, sulbactam).
- AmpC beta-lactamases are chromosomally present in all A. baumannii, but usually expressed at a low level. Promoter mutations cause elevated expression of AmpC beta-lactamases.
- Mutations in penicillin binding proteins also increase resistance to sulbactam.
- Aminoglycoside modifying enzymes or 16s rRNA methyltransferases usually cause aminoglycoside resistance.
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References
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Books:
- Shah, P. L., Herth, F. J., Lee, G., & Criner, G. J. (2018). Essentials of Clinical pulmonology. In CRC Press eBooks. https://doi.org/10.1201/9781315113807
- J. Hodler et al. (eds.), Diseases of the Chest, Breast, Heart and Vessels 2019–2022, IDKD Springer Series, https://doi.org/10.1007/978-3-030-11149-6_6
57 - Shepard, JO. (2019). Thoracic Imaging The Requisites (Requisites in Radiology) (3rd ed.). Elsevier.
- Walker C & Chung JH (2019). Muller’s Imaging of the Chest: Expert Radiology Series. Elsevier.
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- Brown, Jeremy. (2021). Other Bacterial and Fungal Respiratory Bacterial Pathogens. Encyclopedia of Respiratory Medicine, 2nd. Edition. 10.1016/B978-0-08-102723-3.00247-X.
- Evans, TJ. (2021). Streptococcus Pneumoniae. Encyclopedia of Respiratory Medicine, 2nd. Edition. 10.1016/B978-0-08-102723-3.00249-3
- Murray & Nadel: Broaddus, V. C., Ernst, J. D., MD, King, T. E., Jr, Lazarus, S. C., Sarmiento, K. F., Schnapp, L. M., Stapleton, R. D., & Gotway, M. B. (2021). Murray & Nadel’s Textbook of Respiratory Medicine, 2-Volume set. Elsevier.
- Fishman's: Grippi, M., Antin-Ozerkis, D. E., Cruz, C. D. S., Kotloff, R., Kotton, C. N., & Pack, A. (2023). Fishman’s Pulmonary Diseases and Disorders, Sixth Edition (6th ed.). McGraw Hill / Medical.