Does aztreonam cover Enterococcus? An analysis of its antimicrobial spectrum

October 12, 2025 •

2 min read

Based on extensive microbiological studies, aztreonam possesses a narrow spectrum of activity that targets aerobic gram-negative bacteria but lacks efficacy against gram-positive organisms, including Enterococcus species [1, 2]. This intrinsic resistance is a crucial pharmacological characteristic that dictates its appropriate clinical use and the potential for superinfections in treated patients [2].

Quick Summary

Aztreonam is a monobactam antibiotic effective against gram-negative bacteria but lacks activity against gram-positive organisms, including Enterococcus, which is intrinsically resistant due to differences in cell wall structure. Its narrow spectrum can increase the risk of enterococcal superinfection, necessitating alternative treatments for such infections.

Key Points

No Enterococcal Coverage: Aztreonam lacks activity against gram-positive bacteria like Enterococcus species due to its selective binding to penicillin-binding protein 3 (PBP-3) in gram-negative organisms [2].
Intrinsic Resistance: Enterococcus is intrinsically resistant to aztreonam because its PBPs have a low affinity for the drug, a fundamental difference from gram-negative bacteria [2].
Risk of Superinfection: The narrow spectrum of aztreonam can lead to an overgrowth of naturally resistant organisms, including Enterococcus, causing secondary infections [2, 5].
VRE Coverage is Different: While aztreonam is not effective against Enterococcus, other drugs like linezolid or daptomycin are specifically used for vancomycin-resistant enterococci (VRE) [6].
Alternative Treatment is Required: For documented enterococcal infections, alternative antibiotics such as ampicillin, vancomycin, or a combination regimen are necessary [4, 6].
Mechanism-Specific Action: Aztreonam's selective action is a double-edged sword; while it's useful in certain situations (e.g., penicillin allergy), it requires careful consideration to ensure all pathogens are targeted [1, 2].

Understanding Aztreonam's Selective Antimicrobial Action

Aztreonam is a monobactam antibiotic with a narrow spectrum, primarily targeting aerobic gram-negative bacteria [1]. Its action involves inhibiting bacterial cell wall synthesis by binding to penicillin-binding protein 3 (PBP-3) in susceptible gram-negative bacteria, disrupting peptidoglycan cross-linking and causing cell lysis [2].

The Reason for Enterococcal Resistance

Aztreonam is ineffective against Enterococcus because Enterococcus is a gram-positive organism, and its PBPs differ structurally from those in gram-negative bacteria [1, 2]. Aztreonam has little to no affinity for gram-positive PBPs, preventing it from inhibiting cell wall synthesis in Enterococcus and resulting in intrinsic resistance [1, 2].

Clinical Implications: The Risk of Superinfection

The narrow spectrum of aztreonam raises the risk of superinfection [1, 2]. When used for gram-negative infections, it eliminates susceptible bacteria but leaves gram-positive and anaerobic bacteria, like Enterococcus, unaffected [2, 5]. This can lead to the overgrowth of resistant organisms [2, 5]. Studies have documented enterococcal superinfection and colonization following aztreonam therapy, sometimes requiring additional treatment [5].

Alternative Antibiotics for Enterococcal Infections

Treating enterococcal infections requires antibiotics other than aztreonam. Several antibiotics are effective against Enterococcus, depending on the specific species and susceptibility patterns [4, 6]. These may include penicillins (like ampicillin), vancomycin, linezolid, or daptomycin [4, 6].

Comparison of Antibiotic Coverage

Here is a simplified comparison of antibiotic coverage for common bacteria, highlighting the difference between Aztreonam and some drugs effective against Enterococcus:


Antibiotic	Gram-Negative Aerobes	Gram-Positive Aerobes (including Enterococcus)	Anaerobes
Aztreonam	Yes	No	No
Ampicillin	Limited	Yes	No
Vancomycin	No	Yes	No
Linezolid	No	Yes	Yes

Conclusion: The Importance of Selective Targeting

Aztreonam is a useful antibiotic for gram-negative infections, especially in patients with $\beta$-lactam allergies [1, 2]. However, its narrow spectrum means aztreonam does not cover Enterococcus [1, 2]. This necessitates careful prescribing, particularly with polymicrobial infections or when considering superinfection risk [2]. Proper identification of pathogens and selection of appropriate antibiotics, such as ampicillin, vancomycin, or linezolid for enterococcal infections, are crucial [4, 6]. For more details on enterococcal infections, consult resources like the Merck Manuals [4].

Frequently Asked Questions

Aztreonam is a narrow-spectrum antibiotic that only targets and binds to the penicillin-binding proteins (PBPs) of gram-negative aerobic bacteria. Enterococcus, a gram-positive organism, has structurally different PBPs that aztreonam cannot effectively bind to, making it intrinsically resistant [1, 2].

Treating an Enterococcus infection with aztreonam would be ineffective. If the antibiotic is used for a different, susceptible gram-negative infection, it may cause a superinfection by leaving Enterococcus and other resistant organisms to flourish without competition [2, 5].

Yes, but not to extend its own coverage. When treating mixed infections involving both gram-negative and gram-positive bacteria, aztreonam is often combined with another antibiotic that specifically covers gram-positive organisms. It does not gain anti-enterococcal activity itself [2].

For susceptible Enterococcus faecalis infections, standard treatments include aminopenicillins like ampicillin or amoxicillin. Serious infections often require combination therapy, such as ampicillin with an aminoglycoside [4, 6].

For VRE infections, which aztreonam does not cover, treatment options include linezolid, daptomycin, and newer tetracycline derivatives [6].

Aztreonam's usefulness is restricted to its specific gram-negative coverage. It is useful in polymicrobial infections where a gram-negative pathogen is also present, especially in patients with a serious penicillin allergy, but a separate drug must be used to treat the enterococcal component [1, 2].

Aztreonam is a monobactam with a distinct monocyclic $\beta$-lactam ring, giving it a much narrower spectrum of activity than many penicillins and cephalosporins. It primarily targets PBP-3 of gram-negative bacteria, whereas other $\beta$-lactams target a broader range of PBPs in both gram-positive and gram-negative organisms [2, 7].