Is there any evidence of an IV regimen for treating H. pylori in NPO patients?

Comment by InpharmD Researcher

Published clinical studies on the use of intravenous (IV) regimens for the treatment of Helicobacter pylori report IV therapy as a potential management option for patients who are nil per os, with eradication rates varying between 43.8% to 95%. Due to variability in regimens, small sample sizes, and heterogeneity in study locations and thus local resistance rates, an optimal IV regimen for treating H. pylori infection was not identified. In general, the selection of IV therapies should be individualized based on resistance patterns.

Background

A 2024 systematic review by Chau, Milic, and Perrott examined intravenous (IV) antibiotics for the management of Helicobacter pylori (H. pylori) infection. Treatment traditionally consists of oral antibiotics. For patients unable to take oral medications, IV antibiotics may be an option. The search identified 11 studies meeting the criteria (3 randomized controlled trials [RCTs] and 7 prospective cohort studies). The RCTs compared various IV and IV/oral antibiotic regimens, showing eradication rates varying between 43.8% to 95%, although the high eradication rate of 95% was accomplished using a triple therapy regimen (2 IV antibiotics plus IV proton pump inhibitor). However, studies were small and conducted in different eras/locations, using inconsistent regimens. The observational studies demonstrated eradication rates from 13.7% to 100% with IV/oral regimens, but were also limited by small sample sizes and variability. Due to heterogeneity, a meta-analysis was not possible. While IV antibiotics appear feasible when oral therapies are contraindicated, recommended regimens require individualization based on resistance patterns. Overall the review found a lack of robust evidence, but IV therapies may be considered for select patients unable to take oral medications, guided by local resistance data. Larger, higher-quality studies are still needed to better evaluate IV antibiotic options for H. pylori infection. [1]

A 2002 comparative study (N= 51) evaluated the use of short-course eradication therapy for H. pylori in patients admitted with upper gastrointestinal tract bleeding due to a peptic ulcer and had a positive urease test over a 12-month period. Patients received pantoprazole 40 mg IV every 12 hours, metronidazole 500 mg every 8 hours, and amoxicillin-clavulanate 1 g/200 mg every 8 hours for a total of 72 hours. Of the patients treated, 87.5% of patients with duodenal ulcers (n= 40) and 63.6% of patients with gastric ulcers (n= 11) achieved H. pylori eradication (p= 0.066), which was measured via 13C-urea breath test at least 2 months after treatment ended. No notable adverse events or bleeding recurrence were reported during therapy, and no patient withdrew from treatment. Based on these findings, the investigators report that short-course IV therapy may be comparable efficacy-wise to oral treatment, in addition to better tolerability. However, as the study was published in Spanish, the findings were unable to be scrutinized and thus should be considered with caution. [2]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Is there any evidence of an IV regimen for treating H. pylori in strict NPO patients?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-2 for your response.

Intravenous metronidazole-, levofloxacin-containing triple therapy for treating patients with Helicobacter pylori-related active peptic ulcer complications: A pilot study
Design	Pilot study N= 35
Objective	To evaluate the efficacy and safety of intravenous use esomeprazole, metronidazole, and/or levofloxacin in the treatment of Helicobacter pylori (H. pylori)-associated peptic ulcer complications
Study Groups	MTZ dual therapy (n= 8) LEV dual therapy (n= 6) Triple therapy (n= 21)
Inclusion Criteria	Patients aged 18-80 with pyloric obstruction or critical bleeding due to benign peptic ulcer and Helicobacter pylori infection.
Exclusion Criteria	Prior H. pylori eradication treatment, prior gastric surgery, serious illnesses such as liver cirrhosis or chronic kidney disease, pregnancy or lactation, and drug allergies. Patients needing surgery due to active bleeding or obstruction.
Methods	The first group received triple therapy consisting of esomeprazole 40 mg Q8H, levofloxacin 0.5 g daily, and metronidazole 0.2 g Q12H intravenously for 7 days. The second group received dual therapy with either esomeprazole 40 mg Q8H and levofloxacin 0.5 g daily or metronidazole 0.2 g Q12H intravenously for 7 days. After completing the intravenous treatments, all patients took esomeprazole orally at a dose of 20 mg twice daily for an additional month. The patients underwent gastroscopy on the seventh day of intravenous treatment to check the healing of the ulcers. They also had a 13C-urea breath test 4–6 weeks after finishing the oral esomeprazole to confirm if their H. pylori infection had been successfully eradicated.
Duration	Treatment: 7 days, followed by 1 month of oral esomeprazole
Outcome Measures	H. pylori eradication rates confirmed by 13C-urea breath test and ulcer healing confirmed by gastroscopy
Baseline Characteristics		MTZ dual therapy (n= 8)	LEV dual therapy (n= 6)	Triple therapy (n= 21)
	Age, years	51.3	54.1	52.5
	Female	2	1	3
	Smoking	0	0	4
	Alcohol	0	0	0
	Body mass index	23.4	24.1	23.7
	Disease GU DU GU + DU	4 4 0	2 4 0	8 14 1
	Complications Bleeding Obstruction Dropout	8 0 0	6 0 0	20 1 0
Results	Endpoint	MTZ dual therapy (n= 8)	LEV dual therapy (n= 6)	Triple therapy (n= 21)
	H. pylori eradication (95% confidence interval [CI])	50% (21.5% to 78.5%)	33.3% (9.7% to 70.0%)	95% (71.1% to 97.4%)
	The H. pylori eradication rate of both LEV-dual therapy and MTZ-dual therapy was significantly lower than that of triple therapy (p= 0.003, 0.016)
Adverse Events	Adverse events were rare. One case of phlebitis and one case of mild leukopenia occurred in the triple therapy group.
Study Author Conclusions	The intravenous triple regimen, consisting of proton-pump inhibitor, metronidazole, and levofloxacin, could be considered in patients of H. pylori-associated peptic ulcer complications if oral medicine cannot be provided
InpharmD Researcher Critique	Limitations include a small sample size and halted randomization after 22 patients due to lower eradication rates in dual therapy groups. Larger and multicenter studies are required to confirm findings.

References:

Zhang W, Gui Q, Chen J, et al. Intravenous metronidazole-, levofloxacin-containing triple therapy for treating patients with Helicobacter pylori-related active peptic ulcer complications: A pilot study. Helicobacter. 2023;28(2):e12946. doi:10.1111/hel.12946

*Three-day intravenous triple therapy is not effective for the eradication of Helicobacter pylori* infection in patients with bleeding gastro-duodenal ulcer**
Design	Randomized, double-blind, placebo-controlled, prospective study N= 75
Objective	To test the efficacy of an ultra-short intravenous (IV) triple therapy against Helicobacter pylori infection in patients with bleeding peptic ulcer against standard oral 1-week triple therapy
Study Groups	IV (n= 38) Oral (n= 37)
Inclusion Criteria	Patients with peptic ulcers and Helicobacter pylori infection, who provided written informed consent
Exclusion Criteria	Recent antibiotic use (within the month), penicillin allergy, age under 18; presence of cardiovascular, respiratory, kidney, or liver dysfunction
Methods	Patients were randomly assigned to either the intravenous group that received omeprazole (40 mg), clarithromycin (500 mg), and amoxicillin-clavulanic acid (1000/200 mg) IV BID for 3 days followed by oral omeprazole (20 mg) plus placebo BID for 7 days. The oral group received the same initial 3-day IV doses of omeprazole, clarithromycin, and amoxicillin-clavulanic acid, followed by a 7-day course of omeprazole (20 mg), clarithromycin (500 mg), and amoxicillin (1000 mg) twice daily. Gastric biopsies were taken for urease test, and a 13C-urea breath test was conducted after 45 days to confirm H. pylori eradication. Intention-to-treat (ITT) analysis included all 75 randomized patients, with the per-protocol (PP) analysis including 56 patients.
Duration	Enrollment: April 2000 to January 2002 Treatment: 10 days: 3 days of intravenous therapy followed by 7 days of oral therapy for the Intravenous Group; 7 days of oral therapy after initial intravenous placebo in the Oral Group Follow-up: 45 days for outcome assessment
Outcome Measures	Primary: Eradication of H. pylori assessed by a 13C-urea breath test Secondary: Eradication rate in patients with bleeding ulcer and without previous NSAID use, adverse event rates and hemorrhagic relapse
Baseline Characteristics		IV (n= 38)	Oral (n= 37)
	Age, years	53.5	49.4
	Male	78.9%	86.5%
	Hemoglobin, g/dL	11.6	10.9
	Urea, mg/dL	74.5	63.3
	Creatinine, mg/dL	0.95	0.93
	NSAID use	31.6%	16.2%
	Duodenal ulcer	73.7%	70.3%
	NSAID, non-steroidal anti-inflammatory drugs
Results	Endpoint	IV (n= 38)	Oral (n= 37)	Odds ratio (95% confidence interval [CI])	Number needed to treat (95% CI)
	Eradication rates ITT PP	19/38 (50%) 14/28 (50%)	29/37 (78.4%) 24/28 (85.7%)	3.6 (1.32 to 9.94) 6 (1.6 to 21)	4 (3 to 13) 3 (2 to 8)
	Eradication rate in bleeding ulcer patients without prior NSAID use ITT PP	14/26 (53.8%) 11/20 (55%)	25/31 (80.3%) 20/24 (83.3%)	3.57 (1.1 to 11.6) 4.1 (1.02 to 16.4)	4 (2 to 33) 4 (2 to 53)
Adverse Events	Phlebitis was slightly more frequent in the intravenous group (18.4%) compared to the oral group (5.4%) (p= 0.083), although other adverse events were not statistically significant between groups.
Study Author Conclusions	An ultra-short, 3-day, intravenous, triple therapy containing omeprazole, clarithromycin and amoxicillin–clavulanic acid cannot be recommended as an effective eradication regimen for H. pylori infection related to haemorrhagic gastro-duodenal ulcer.
InpharmD Researcher Critique	The study had a smaller sample size than anticipated, possibly affecting the power. The primary hypothesis was refuted, demonstrating that the 3-day intravenous therapy was less effective. Statistical analysis was robust, but there were issues with compliance among some patients. Future research could explore different combinations or durations of intravenous therapies.

References:

Romero-Gómez M, Martínez-Delgado C, Herg kk ueta P, et al. Three-day intravenous triple therapy is not effective for the eradication of Helicobacter pylori infection in patients with bleeding gastro-duodenal ulcer. Aliment Pharmacol Ther. 2003;18(10):1023-1029. doi:10.1046/j.1365-2036.2003.01763.x