Aztreonam: Uses, Dosage, Side Effects and Interactions

Aztreonam stands out in the world of antibiotics as the first and most widely used monobactam. With its unique structure and spectrum of activity, it offers tailored therapy options for certain hard-to-treat infections—especially those caused by resistant Gram-negative bacteria. As resistance to other antibiotics rises globally, understanding aztreonam’s role, optimal use, and potential pitfalls is more important than ever. This comprehensive guide explores the uses, dosage, side effects, and interactions of aztreonam, synthesizing up-to-date research to inform patients, clinicians, and anyone interested in modern medicine.

Uses of Aztreonam

Aztreonam’s clinical value is rooted in its specificity: it powerfully targets Gram-negative aerobic bacteria, including notorious hospital-acquired pathogens like Pseudomonas aeruginosa. Its resistance to many beta-lactamases—enzymes that often confer antibiotic resistance—makes it a go-to option for challenging infections. With the rise of multidrug-resistant organisms, aztreonam is also being revived as part of combination therapies, especially against metallo-β-lactamase (MBL) producers, offering hope where few antibiotics remain effective.

Indication	Main Pathogens	Key Notes	Source(s)
Serious infections	Gram-negative aerobes	Effective against P. aeruginosa, Enterobacteriaceae; not active vs Gram-positives/anaerobes	1 4
Cystic fibrosis	Pseudomonas aeruginosa	Used during pulmonary exacerbations	7 11
Resistant bacteria	MBL/ESBL producers	Often combined with avibactam or ceftazidime-avibactam	2 3 6
Penicillin allergy	Various Gram-negatives	Minimal cross-reactivity with other beta-lactams	12

Table 1: Clinical Uses of Aztreonam

Targeted Activity Against Gram-Negative Bacteria

Aztreonam is strikingly effective against a broad range of aerobic Gram-negative bacilli—especially Enterobacteriaceae and Pseudomonas aeruginosa—but it is largely inactive against Gram-positive bacteria and anaerobes. This focused spectrum is advantageous in hospital settings where Gram-negative pathogens cause severe infections, including pneumonia, urinary tract infections, sepsis, and osteomyelitis 1 4. Because aztreonam does not impact the normal gut flora as much as broader-spectrum agents, it reduces the risk of secondary infections such as Clostridioides difficile.

Role in Cystic Fibrosis

For patients with cystic fibrosis (CF), aztreonam is used to manage pulmonary exacerbations, particularly those involving P. aeruginosa—a major cause of morbidity in CF. Clinical studies demonstrate significant reductions in bacterial counts and improvements in clinical status, though eradication is often temporary 7 11.

Combating Multidrug-Resistant Organisms

With the emergence of multidrug-resistant (MDR) Gram-negative bacteria, aztreonam has gained renewed attention. Its unique stability to metallo-β-lactamases (MBLs) makes it a critical agent in combination therapies for infections caused by these organisms. Combinations with avibactam, ceftazidime-avibactam, and meropenem-vaborbactam have shown promising synergy in both laboratory and early clinical settings 2 3 6. These combinations are especially important for treating MBL-producing Enterobacteriaceae and Stenotrophomonas maltophilia, where few alternatives exist.

Use in Penicillin-Allergic Patients

One of aztreonam’s notable features is its minimal immunologic cross-reactivity with penicillins and cephalosporins, making it a safe option for patients with serious beta-lactam allergies 12. This opens a therapeutic avenue for individuals who would otherwise have limited antibiotic choices.

Dosage of Aztreonam

Dosing aztreonam correctly is crucial for both efficacy and safety. The drug’s pharmacokinetic properties, renal elimination, and the need to maintain effective concentrations above the minimum inhibitory concentration (MIC) all influence dosing strategies. Adjustments may be necessary in special populations, such as those with renal impairment or cystic fibrosis.

Patient Group	Typical Dose	Dose Adjustment Needed	Source(s)
Adults (normal renal)	1-2 g IV every 8 hours	No	1 9 15
Renal impairment	Reduce dose based on CrCl	Yes	8
Cystic fibrosis	Up to 200 mg/kg/day IV	Higher clearance; monitor	7 11
Combination therapy	Varies (e.g., 2 g q6h with avibactam)	Adjust for renal function	6 10

Table 2: Common Dosing Strategies for Aztreonam

Standard Adult Dosing

For most serious Gram-negative infections in adults with normal kidney function, aztreonam is administered intravenously at 1 to 2 grams every eight hours. These doses achieve serum and urine concentrations far exceeding the MICs for most susceptible pathogens, including Enterobacteriaceae and many strains of P. aeruginosa 1 9 15.

Dosing in Renal Impairment

Since aztreonam is primarily eliminated by the kidneys—about 58–75% is excreted unchanged in the urine—dose reductions are essential for patients with decreased renal function 8 9. The elimination half-life extends from about 2 hours in normal renal function to 6 hours in severe impairment. Nomograms and guidelines are available to adjust dosing based on creatinine clearance, minimizing the risk of drug accumulation and toxicity 8.

Special Populations: Cystic Fibrosis

Patients with cystic fibrosis clear aztreonam more rapidly due to increased renal clearance. Higher or more frequent doses (e.g., up to 200 mg/kg/day divided into four doses) may be required, and therapeutic monitoring is advised to ensure adequate drug exposure 7 11.

Combination Regimens for Resistant Infections

For infections caused by MBL- or ESBL-producing organisms, aztreonam is often paired with avibactam or ceftazidime-avibactam. Clinical trials have tested regimens such as aztreonam 2 g every 6 hours (1-hour infusion), with avibactam 375–600 mg every 6 hours. For complicated intra-abdominal infections, dosing regimens of aztreonam/avibactam 1500/500 mg every 6 hours (following a loading dose) have been used, with dose adjustments for patients with lower creatinine clearance 6 10.

Pharmacokinetic Considerations

• Half-life: ~2 hours (normal renal function)
• Volume of distribution: ~0.17 L/kg
• Serum concentrations: Well above MICs for 8 hours post-dose at 1–2 g IV 9
• Excretion: Primarily renal; minimal hepatic metabolism 8 9

Side Effects of Aztreonam

Aztreonam has a generally favorable safety profile, with most side effects being mild and reversible. Its narrow spectrum reduces the risk of superinfections and gut flora disruption. However, as with all antibiotics, adverse events can occur and must be monitored, especially in vulnerable populations.

Side Effect	Frequency/Severity	Notes	Source(s)
GI upset (diarrhea)	Common, mild	Less disruption of gut flora	4 10
Liver enzyme elevations	Occasional, transient	Not typically serious	11 10
Hypersensitivity	Rare, usually mild	Minimal cross-reactivity	12
Serious reactions	Very rare	No serious events in studies	1 10

Table 3: Common and Notable Side Effects of Aztreonam

Gastrointestinal and Hepatic Effects

The most frequently reported side effects are mild gastrointestinal complaints, such as diarrhea and nausea. Because aztreonam does not affect anaerobes, it is less likely to cause significant alterations in the gut microbiome or lead to C. difficile infection compared to broad-spectrum agents 4. Transient elevations in liver enzymes are occasionally observed, particularly in patients with cystic fibrosis or during combination therapy; these are rarely clinically significant and usually resolve after discontinuation 10 11.

Hypersensitivity and Allergic Reactions

Aztreonam is notable for its low risk of allergic reactions, especially in patients with known penicillin or cephalosporin allergies. Immunologic studies show minimal IgE or IgG cross-reactivity, making it a safe alternative in these populations 12. Anaphylaxis is exceedingly rare.

Other Adverse Events

Serious adverse events are rare. In clinical trials and post-marketing experience, no consistent pattern of severe toxicity has emerged. Some patients may experience phlebitis at the infusion site or mild skin reactions 1 10.

Safety in Special Combinations

When used in combination with avibactam, ceftazidime-avibactam, or other agents to combat resistant organisms, the safety profile remains similar to aztreonam alone, with no new or unexpected adverse events reported in early-phase studies 10.

Interactions of Aztreonam

Aztreonam’s interaction profile is relatively straightforward, with few clinically significant drug-drug interactions. However, its use in combination with other antibiotics—either to broaden antimicrobial coverage or enhance efficacy—warrants discussion.

Interaction Type	Effect	Clinical Notes	Source(s)
Beta-lactams	Additive or synergistic	Synergy with ceftazidime, avibactam; rarely antagonistic	2 3 13 14
Aminoglycosides	Additive/synergistic	Alternative to aminoglycosides for Gram-negatives	1 13
Fluoroquinolones	Synergistic (variable)	Enhanced activity vs P. aeruginosa	14
Immunologic	Minimal cross-reactivity	Safe in penicillin-allergic patients	12

Table 4: Key Drug Interactions with Aztreonam

Antibiotic Combinations: Expanding the Spectrum

Aztreonam is frequently combined with other antibiotics to either expand the antimicrobial spectrum or achieve synergistic killing:

• With Beta-lactamase Inhibitors (e.g., avibactam): Critically important in treating infections by bacteria that produce MBLs and ESBLs. The combination restores activity against organisms that would otherwise be resistant 2 3 6.
• With Ceftazidime-Avibactam or Meropenem-Vaborbactam: Laboratory studies and clinical anecdotes highlight strong synergy, especially in multidrug-resistant Enterobacteriaceae 2.
• With Other Beta-lactams and Fluoroquinolones: Checkerboard studies show frequent synergy or partial synergy, particularly with ceftazidime, cefepime, and gatifloxacin against P. aeruginosa 14.
• With Aminoglycosides: Additive or synergistic effects, serving as a safer alternative in patients at risk for aminoglycoside toxicity 1 13.

Antagonism Is Rare

Most antibiotic combinations with aztreonam are either additive or synergistic. Antagonism is rare but has been observed in specific pairings (e.g., with latamoxef against Proteus vulgaris) 13. These exceptions are not typically encountered in clinical practice.

Immunologic Interactions

Unlike other beta-lactams, aztreonam’s unique side chain structure means it does not readily cross-react with penicillin- or cephalosporin-specific antibodies, reducing the risk of allergic cross-reactions 12.

Conclusion

Aztreonam remains a valuable tool in the fight against Gram-negative infections—especially as multidrug-resistant bacteria continue to threaten global health. Its unique structure, targeted activity, and favorable safety profile make it both a reliable monotherapy and a crucial partner in combination regimens for highly resistant organisms. When used judiciously and dosed appropriately, aztreonam offers clinicians a powerful, flexible option with minimal risk for adverse reactions or drug interactions.

Key Points:

• Highly Effective for Gram-Negative Infections: Targets aerobic Gram-negative bacteria, including MDR organisms 1 4.
• Minimal Cross-Reactivity: Safe for patients with penicillin or cephalosporin allergies 12.
• Flexible Dosing: Requires adjustment in renal impairment and CF; combination regimens increasingly important 7 8 10.
• Generally Safe: Side effects are mild and self-limited; serious reactions are rare 1 10 11.
• Synergistic Potential: Effective in combination with avibactam, ceftazidime-avibactam, and others for resistant infections 2 3 6 14.

Aztreonam’s role is evolving alongside the ever-changing landscape of antibiotic resistance. Continued research and careful stewardship will ensure it remains a cornerstone in the treatment of severe Gram-negative infections.