By Sophia Vaill, PharmD Candidate

Historically considered a disease associated with honey and environmental exposures, infant botulism has entered a new era of concern as recent Centers for Disease Control and Prevention (CDC) investigations link powdered infant formula to two multistate outbreaks.¹ The most recent alert regarding Nara Organics Whole Milk Organic Infant Formula is ongoing and includes four cases reported in 3 states as of July 6, 2026.² This comes after another outbreak last year, where ByHeart Whole Nutrition Infant Formula resulted in 48 cases of infant botulism across 17 states between December 24, 2023 and November 29, 2025.³ Importantly, all infants to date have received botulism immunoglobulin and survived.^2,3

Signs and Symptoms of Infant Botulism

Infant botulism occurs when an infant ingests Clostridium botulinum, and the spores become active in the intestine and begin producing botulinum neurotoxin.¹ This neurotoxin inhibits the release of acetylcholine, resulting in muscle paralysis.^4,5 Clinical presentation differs between infants and older pediatric patients. In infants, constipation is the most common initial symptom, followed by poor feeding, hypotonia, and a weak cry.⁴ This is in contrast to children and adolescents who typically experience dysphagia, blurred vision, diplopia, and weakness.⁶

Infant Botulism Treatment

The American Academy of Pediatrics (AAP) and CDC both recommend human-derived antitoxin, with  BabyBIG^® (botulism immune globulin), for infants whose clinical presentation is consistent with infant botulism.^1,4,7 Botulism immune globulin is made of human-derived IgG antibodies collected through plasma donations from immunized donors with high levels of antibodies against C. botulinum A and B toxins.⁷ There are a limited number of available donors as they are individuals previously vaccinated with a recombinant botulinum vaccine targeting serotypes A and B.⁷

The safety and efficacy of botulism immune globulin were demonstrated in a 5-year, randomized, double-blind, placebo-controlled trial in California involving infants with laboratory-confirmed infant botulism. A total of 122 infants were administered treatment (n=59) or placebo (n=63) within 3 days of hospital admission.⁸ Those treated with botulism immune globulin had a shorter mean duration of intensive care (5.0 vs 1.8 weeks; p<0.001), mechanical ventilation (4.4 vs 1.8 weeks; p=0.01), non-oral feeding (reduction of 10.0 vs 3.6 weeks; p<0.001), and hospital length of stay (5.7 vs 2.6; p<0.001). Researchers also found an average $88,600 per patient reduction in hospital charges ($163,400 vs $74,800; p<0.001). No serious adverse events were reported with the botulism immune globulin therapy.⁸

Following this initial trial, the botulism immune globulin was administered as an open label 6-year study.  This included 382 infant botulism cases. Their data from this study reinforces early intervention had shorter hospital duration (average 2.2 weeks overall; 2.9 weeks in those treated days 4-7 versus 2.0 weeks in those treated within 3 days).⁸

Treatment Initiation

If infant botulism is suspected, a clinical consultation with the California Infant Botulism Treatment and Prevention Program (IBTPP) is required to determine patient eligibility.⁹ All references note that treatment should not be delayed while waiting on laboratory confirmation.^1,4,6 The medication is shipped from California, and fee for botulism immune globulin is $69,300 as of July 1, 2025.¹⁰

Botulism Immune Globulin: Administrative and Drug-Interaction Considerations

The botulism immune globulin requires reconstitution with 2 mL sterile water.⁷ Timing is important, as it may take 30 minutes to get into suspension, and administration to the patient must be initiated within 2 hours of reconstitution.¹¹ The recommended dose is 50 mg/kg and it should be infused at 0.5 ml/kg/hour. The product should be infused via a dedicated intravenous line and with a 18 µm filter.⁷ Like with any immunoglobulin, patients should be monitored for infusion-related or hypersensitivity reactions.

For those who are 6 months or older, it is important to communicate that it is recommended that live immunizations are deferred for 6 months following botulism immune globulin therapy.  The specific antibody- immunization concerns in this age group, include varicella and measles, mumps and rubella vaccines, which are both routinely recommended routinely for those 12-15 months of age per the AAP and CDC.^12,13 This deferment recommendation, is to avoid interference (e.g., decreased vaccine immune response) from passively transferred antibodies.⁷

It is recommended to avoid aminoglycoside antibiotics, as they may potentiate and worsen the neuromuscular paralysis caused by the neurotoxin. An unfortunate cautionary case in the literature describes an increase in paralysis and death in a 5-month-old later found to have C. botulinum Type A, who treated with gentamicin for sepsis.¹⁴

Key Takeaways Regarding Botulism Immune Globulin

Prompt initial detection and timely treatment with botulism immune globulin are essential to improving patient outcomes. Current recommendations emphasize initiating treatment based on clinical symptoms and consultation rather than delaying therapy to wait for confirmation. Pharmacists should be familiar with and educate others to ensure proper preparation, administration, monitoring, and, if appropriate, delay of vaccinations.

About the author: Sophia Vaill, is a Doctor of Pharmacy candidate at the University of Connecticut. This post was written as part of her Advanced Pharmacy Practice Experience under the guidance of her professor, Jennifer Girotto PharmD, BCPPS, BCIDP, who also reviewed and edited the piece.

References

1. American Academy of Pediatrics Committee on Infectious Diseases. Botulism and infant botulism (Clostridium botulinum). Red Book: 2024–2027 Report of the Committee on Infectious Diseases (33rd Edition). American Academy of Pediatrics; 2024. https://publications.aap.org/redbook/book/755/chapter-abstract/14076234/Botulism-and-Infant-Botulism-Clostridium-botulinum
2. Centers for Disease Control and Prevention. Investigation Update on Infant Botulism Outbreak, June 2026. https://www.cdc.gov/botulism/outbreaks-investigations/infant-formula-june-2026/investigation.html. Updated 2026. Accessed July 7, 2026
3. Centers for Disease Control and Prevention. Investigation Update: Infant Botulism Outbreak, November 2025. https://www.cdc.gov/botulism/outbreaks-investigations/infant-formula-nov-2025/investigation.html. Updated 2026. Accessed July 2, 2026
4. Centers for Disease Control and Prevention. Clinical Overview of Infant Botulism. https://www.cdc.gov/botulism/hcp/clinical-overview/infant-botulism.html. Updated 2024. Accessed July 2, 2026
5. Cagan E, Peker E, Dogan M, Caksen H. Infant botulism. Eurasian J Med. 2010;42(2):92–94. doi:10.5152/eajm.2010.25
6. Rao AK, Sobel J, Chatham-Stephens K, Luquez C. Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021. MMWR Recomm Rep. 2021;70(2):1–30. doi:10.15585/mmwr.rr7002a1
7. California Department of Public Health. BabyBIG [Botulism Immune Globulin Intravenous (Human) (BIG-IV)]. Prescribing information. 2021. https://www.fda.gov/media/150406/download
8. Arnon SS, Schechter R, Maslanka SE, Jewell NP, Hatheway CL. Human botulism immune globulin for the treatment of infant botulism. N Engl J Med. 2006;354(5):462–471. doi:10.1056/NEJMoa051926
9. California Department of Public Health. How to Obtain Clinical Consultation and Order BabyBIG®. Infant Botulism Treatment and Prevention Program Web site. https://www.infantbotulism.org/physician/obtain. Updated 2026. Accessed July 2, 2026
10. California Department of Public Health. Postponement of BabyBIG® Fee Increase. 2025. https://www.cdph.ca.gov/Programs/OLS/CDPH%20Document%20Library/DPH-25-005-BabyBIG_Fee_FP.pdf
11. California Department of Public Health. Instructions for Use of BabyBIG®. Infant Botulism Treatment and Prevention Program Web site. https://www.infantbotulism.org/pharmacist/instruction. Updated 2026. Accessed July 2, 2026
12. American Academy of Pediatrics Committee on Infectious Diseases. AAP Immunization Schedule. Red Book: Report of the Committee on Infectious Diseases 2024 – 2027 Web site. https://publications.aap.org/redbook/resources/15585/AAP-Immunization-Schedule. Updated 2026. Accessed July 17, 2016
13. Centers for Disease Control and Prevention. Child and Adolescent Immunization Schedule by Age (Addendum updated July 2, 2025). https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html. Updated 2025. Accessed July 17, 2016
14. Santos JI, Swensen P, Glasgow LA. Potentiation of Clostridium botulinum toxin aminoglycoside antibiotics: clinical and laboratory observations. 1981;68(1):50–54

 

 

By: Jenna-Lynn Kelley, PharmD Candidate

Real-world pediatric outcomes data have finally closed a problematic evidence gap.¹ Morrisette and colleagues recently published a descriptive study showcasing the efficacy of ceftazidime/avibactam in pediatric drug-resistant Gram-negative infections in the Open Forum Infectious Diseases journal.¹ This addition to pediatric literature is the missing puzzle piece that will give pharmacists confidence when considering ceftazidime/avibactam for these challenging infections in children.

Ceftazidime/Avibactam from a Real-World Perspective

The promising results of ceftazidime/avibactam in real-world pediatric practice settings published in April 2026 solidify its well-established place in therapy.^1,2 In this retrospective observational cohort study, seventy-three of 100 (73%) pediatric patients achieved clinical success without experiencing microbiologic or clinical recurrence within 30 days of discontinuation or development of resistance within 90 days of initiation.¹ Furthermore, most patients did not have a recurrent infection within 30 days of ceftazidime/avibactam discontinuation (94%) and clinically improved without the need for treatment modification due to suspected treatment failure (97%).¹ There were also several pre-defined adverse events potentially attributable to ceftazidime/avibactam (e.g. acute kidney injury, Clostridioides difficile infection, hepatotoxicity, gastrointestinal and central nervous system effects), however authors did not identify any of these adverse events in the study.¹ All-cause mortality was reported in 16 (16%) patients.¹ Though the included cohort was mostly White (62%), it was considerably well-generalized across age and gender.¹ As expected, infections were mainly caused by highly prevalent drug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and Klebsiella pneumoniae.^1-3 Interestingly, many patients had baseline hematologic conditions and other immunodeficiencies (42%) and a long median length of hospital stay (42 days, IQR 17-139.5 days) despite a majority of community admissions (77%), implying that pediatric oncology patients potentially made up a decent subset of the cohort.¹

The Trusted Role of Ceftazidime/Avibactam

Current evidence-based literature recognizes ceftazidime/avibactam as a reliable antimicrobial agent for drug-resistant Gram-negative infections, though the majority of evidence has largely focused on adult patients. 2024 IDSA guidance strongly recommends its use in both adult and pediatric antimicrobial-resistant infections caused by pathogens such as P. aeruginosa and CRE, though pediatric dosing recommendations are not provided.² Several primary sources, as shown below in Table 1, have also reported optimistic results regarding the use of ceftazidime/avibactam in pediatric patients. Despite the demonstrated success of ceftazidime/avibactam in these descriptive studies, the small sample sizes and narrow focus on pediatric intensive care units limits their scope. The real-world outcomes newly published in April 2026 enhance the impact of these studies by offering a larger cohort and broader demographics.

Table 1. Primary sources on ceftazidime/avibactam in pediatric patients 4-7
First Author, Year	Study Design	Population	Results
Havan M, 20264	Retrospective observational study	PICU, 1 month-18 years (n=21), CZA for confirmed MDR or PDR GN infection	85.7% microbiological clearance
Araujo da Silva AR, 20245	Retrospective observational study	PICU, 0-18 years (n=37), CZA > 24 hours	4 / 5 carbapenem-resistant GN microbiological clearance
Bradley JS, 20196	Phase II, single-blind randomized controlled trial	Hospitalized, 3 months – 18 years (n=83), complicated intra-abdominal infection	90% favorable clinical and microbiological response in both arms
Bradley JS, 20197	Phase II, single-blind randomized controlled trial	Hospitalized,  3 months – 18 years (n=95), complicated urinary tract infection	95% favorable outcomes in both arms

Abbreviations. CZA: ceftazidime/avibactam; GN: Gram-negative; MDR: multidrug-resistant; n = sample size; PDR: pandrug-resistant; PICU: pediatric intensive care unit

The Benefit of Ceftazidime/Avibactam Validation in Pediatric Patients

Antimicrobial resistance is climbing at an alarming rate, contributing to an estimated 1.3 million deaths worldwide in 2019.^1-3,8,9 The CDC considers multidrug-resistant (MDR) P. aeruginosa a serious national threat and carbapenem-resistant Enterobacterales (CRE) an urgent national threat, making it critical to effectively treat resulting infections.³ The prevalence of inappropriate antibiotic prescribing makes this feat increasingly challenging.^8,10 Given the concerning ascent of drug resistance in Gram-negative infections, the optimistic outcomes from this observational cohort study are a relieving addition to current pediatric literature.

Practical Points for Pharmacists

The newly published pediatric outcomes data supporting the use of ceftazidime/avibactam in drug-resistant Gram-negative infections in children is a win, but the impact on practice depends on the ability to uphold ideal antimicrobial stewardship principles such as applying evidence-based dosing and administration. Most patients in the study received 50mg ceftazidime/kg (44%) or 2g ceftazidime (40%) every 8 hours, consistent with FDA-approved dosing, but the duration was less than the 3-hour prolonged infusion recommended by Lockowitz and colleagues to maximize the pharmacodynamics of the medication (when used for infections outside of the central nervous system).^1,9,11-13 Further details regarding ceftazidime/avibactam’s use for specific drug-resistant Gram-negative infections can be found in this prior blog post by Galicia.⁹

Key Takeaways

An abundance of data supports the use of ceftazidime/avibactam in pediatric drug-resistant Gram-negative infections. To continue to preserve this antibiotic, it should only be used when necessary and pharmacists should remember to utilize appropriate dosing and prolonged infusion time (outside of central nervous system infections). This will ensure that ceftazidime/avibactam remains a reliable antimicrobial agent for drug-resistant Gram-negative infections in the pediatric population.

Jenna-Lynn Kelleyis a Doctor of Pharmacy candidate at the University of Connecticut. This post was written as part of her Advanced Pharmacy Practice Experience under the guidance of her professor, Jennifer Girotto PharmD, BCPPS, BCIDP, who also reviewed and edited the piece.

References

1. Morrisette T, Stimes GT, Alvira-Arill GR, et al. Multicenter evaluation of ceftazidime/avibactam in pediatric patients across the united states: Real-world insights into the management of drug-resistant gram-negative infections. Open Forum Infect Dis. 2026;13(4):ofag177. doi: 10.1093/ofid/ofag177.
2. Tamma PD, Heil EL, Justo JA, Mathers AJ, Satlin MJ, Bonomo RA. Infectious diseases society of america 2024 guidance on the treatment of antimicrobial-resistant gram-negative infections. Clin Infect Dis. 2024. doi: 10.1093/cid/ciae403.
3. U.S. Centers for Disease Control and Prevention. Antimicrobial resistance rates in the united states, 2021-2022. Updated July 2024. https://www.cdc.gov/antimicrobial-resistance/media/pdfs/antimicrobial-resistance-threats-update-2022-508.pdf. Accessed July 2026.
4. Havan M, Arga G, Bulbul YE, et al. Ceftazidime-avibactam for multidrug and pandrug-resistant gram-negative infections in critically ill children: A single-center pediatric intensive care experience. Eur J Pediatr. 2026;185(4):219. doi: 10.1007/s00431-026-06862-1.
5. Araujo da Silva AR, Quijada R. Use of ceftazidime-avibactam in children admitted to pediatric intensive care units. Children (Basel). 2024;11(6):664. doi: 10.3390/children11060664.
6. Bradley JS, Broadhurst H, Cheng K, et al. Safety and efficacy of ceftazidime-avibactam plus metronidazole in the treatment of children ≥3 months to Pediatr Infect Dis J. 2019;38(8):816–824. doi: 10.1097/INF.0000000000002392.
7. Bradley JS, Roilides E, Broadhurst H, et al. Safety and efficacy of ceftazidime-avibactam in the treatment of children >/=3 months to Pediatr Infect Dis J. 2019;38(9):920–928. doi: 10.1097/INF.0000000000002395.
8. Versporten A, Bielicki J, Drapier N, Sharland M, Goossens H, ARPEC project group. The worldwide antibiotic resistance and prescribing in european children (ARPEC) point prevalence survey: Developing hospital-quality indicators of antibiotic prescribing for children. J Antimicrob Chemother. 2016;71(4):1106–1117. doi: 10.1093/jac/dkv418.
9. Galicia M. Treatment of multidrug-resistant organisms in children: Challenges and current strategies. Published December 16, 2025. Accessed July 13, 2026. https://pharmacy.uconn.edu/2025/12/16/treatment-of-multidrug-resistant-organisms-in-children-challenges-and-current-strategies/.
10. Levy ER, Swami S, Dubois SG, Wendt R, Banerjee R. Rates and appropriateness of antimicrobial prescribing at an academic children’s hospital, 2007-2010. Infect Control Hosp Epidemiol. 2012;33(4):346–353. doi: 10.1086/664761.
11. Avycaz (ceftazidime and avibactam) for injection. Prescribing Information. Abbvie, Inc. Updated April 2025. Accessed July 13, 2026. www.accessdata.fda.gov
12. Lockowitz CR, Hsu AJ, Chiotos K, et al. Suggested dosing of select beta-lactam agents for the treatment of antimicrobial-resistant gram-negative infections in children. J Pediatric Infect Dis Soc. 2025;14(2):piaf004. doi: 10.1093/jpids/piaf004.
13. Ellis JM, Kuti JL, Nicolau DP. Use of monte carlo simulation to assess the pharmacodynamics of beta-lactams against pseudomonas aeruginosa infections in children: A report from the OPTAMA program. Clin Ther. 2005;27(11):1820–1830. doi: 10.1016/j.clinthera.2005.11.007.