CAT BITE Antibiotic Prophylaxis for the Hand/Forearm (CATBITE)

University of Missouri (MU)

Status and phase

Enrolling

Phase 4

Conditions

Cat Bite

Arm Injury

Hand Injuries

Anti-bacterial Agents

Infection, Bacterial

Treatments

Drug: Amoxicillin/clavulanate

Procedure: Wound management

Drug: Ciprofloxacin

Other: Placebo (microcrystalline cellulose)

Drug: Clindamycin

Study type

Interventional

Funder types

Other

Identifiers

NCT05846399

2092043

Details and patient eligibility

About

Cat bites are puncture wounds that have the potential to seed bacteria deep within the joint capsule, periosteum, and bone. The hand is the most common site of bite injuries. Pasteurella multocida is the is the most common organism isolated from the mouths of cats that can cause infections after a bite. Prophylactic antibiotics are often recommended with amoxicillin-clavulanate for 3-5 days to decrease the incidence of developing an infection. However, only one randomized controlled clinical trial consisting of 12 patients has been performed to justify this course of treatment, raising the possibility that the use of antibiotics could be reduced or even eliminated. Investigators will compare different durations of prophylactic antibiotics and a placebo control for cat bites to the hand/forearm presenting to the Emergency Department, Urgent Care, Plastic Surgery Clinic using a randomized, controlled, double-blind clinical trial. Participants presenting to the University of Missouri Hospital Emergency Department, Missouri University (MU) Healthcare Urgent Care, Plastic Surgery Clinic over the next year will be offered the chance to enroll if they meet the inclusion/exclusion criteria. For inclusion, participants will be >18 years of age, have cat bites to the hand or distal to elbow, and present within 24 hours of the cat bite injury. Participants must not present with active local or systemic infections, have received antibiotics within the past 30 days, or be immunocompromised (primary and secondary immunodeficiencies). Participants will be randomized to one of three treatment arms (placebo; amoxicillin-clavulanate 1 day; amoxicillin-clavulanate 5 days). Outcomes are the development of an infection at the location of the cat bite and/or systemic infection, adverse effects of interventions, disability assessed by Quick Disabilities of Arm, Shoulder and Hand (QuickDASH) scores, and quality of life (QOL) assessed by HAND Questionnaire (HAND-Q) scores. Infection will be assessed at day 0, day 2, day 7+/-2, day 14+/-2, and day 30+/-2 by vital signs, laboratory values, physical examination and with an infrared and digital camera. All measures will be within the standard of care, apart from the infrared camera, QuickDASH, and HAND-Q scores. The anatomic locations of cat bites to the hand/forearm will be assessed for correlations with infections.

Full description

Cat bites have been reported as the second most common domestic animal bite in the United States, ranging from 5%-15% of all bites. The hand is the most common site of bite injuries. Cat bites are puncture wounds that have the potential to seed bacteria deep within the joint capsule, periosteum and bone. As a result, infection is a serious complication, reported in 30%-50% of cat bites. The median time to signs and symptoms of infection following a cat bite is typically short (approximately 12 hours). Direct healthcare costs associated with management of cat and dog bites in the United States estimate >$850,000,000 annually and do not consider the indirect costs associated with time off work, rehabilitation, and permanent impairment.

The average cat bite wound culture yields five types of bacterial isolates. Mixed aerobic and anaerobic bacteria are observed in 60% of cases. Pasteurella multocida is the is the most common organism isolated from the mouths of cats that can cause infections after a bite. Pasteurella species are isolated from 75% of cat bite wounds, and the incubation period for Pasteurella infection is one to three days. Capnocytophaga canimorsus can cause bacteremia and fatal sepsis after animal bites, especially in patients with asplenia, alcoholism, or underlying hepatic disease. The incubation period for Capnocytophaga infection is one to three days. Bartonella henselae may be transmitted via the bite of an infected cat and contact with cat saliva via broken skin or mucosal surfaces. The incubation period for Bartonella infection is 7 to 14 days. Anaerobes isolated from dog and cat bite wounds include Bacteroides species, fusobacteria, Porphyromonas species, Prevotella species, cutibacteria (formerly propionibacteria), and peptostreptococci.

Prophylactic antibiotics are often recommended to decrease the incidence of developing an infection. Broad antibiotic coverage is recommended to address the polymicrobial nature of common oral flora and bite infections. Pasteurella species are generally susceptible to penicillin and ampicillin, but staphylococci and anaerobic species often produce beta-lactamase, which provides resistance to these antibiotics. Adding a beta-lactamase inhibitor significantly increases the effectiveness of these antibiotics, and amoxicillin-clavulanate is the oral antibiotic of choice for human, dog, and cat bites. Infectious Diseases Society of America (IDSA) guidelines recommend antibiotic prophylaxis with amoxicillin-clavulanate 875-125mg twice daily (BID) for 3-5 days or ciprofloxacin 500-750mg BID + clindamycin 300-450mg three times daily (TID) if a participant has a penicillin allergy. However, only one randomized controlled clinical trial (RCT) has been performed to date to assess the efficacy of prophylactic antibiotics following cat bites. Adult participants with uninfected full-thickness wounds presenting within 24 hours of injury to the emergency department were considered. Participants were randomly assigned to receive oxacillin 500mg four times daily (QID) for five days (n=5) or identically appearing placebo (n=6). Four of six participants receiving placebo, but none of the five participants receiving oxacillin, developed a wound infection (P = 0.045).

Immunocompetent adult participants presenting within 24 hours of a cat bite without any signs or symptoms of infection may benefit from advances in wound care alone or only need a maximum of 24 hours of antibiotic prophylaxis. Furthermore, a Cochrane review aggregating data from clinical trials from the literature concluded, "There is no evidence that the use of prophylactic antibiotics is effective for cat or dog bites." The investigators' hypothesis is that administration of 5 days of prophylactic antibiotics will not reduce the incidence of infection in participants evaluated and treated within 24 hours of cat bite injury, who do not exhibit signs of an active infection.

Enrollment

72 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Patients greater or equal to 18 years of age.
Bitten by a cat.
Location of bite is the hand and/or forearm (distal to elbow).
Presenting <24 hours following a cat bite to the hand/forearm.
English speaking

Exclusion criteria

Patients who present with active local or systemic infections
1. Purulent drainage from the cat bite
2. Redness AND swelling at the location of the cat bite
Having a fever >100.4° F or >38° C)-Received antibiotics within the past 30 days
Received antibiotics within the past 30 days
Patients unwilling to take study medication
Patients unwilling to attend scheduled follow-up evaluations or complete study forms
Pregnant Women
Type I hypersensitivity reaction to any of the study interventions
Immunocompromised patients (primary and secondary immunodeficiencies) Primary
Autoimmune Lymphoproliferative Syndrome (ALPS)
Autoimmune Polyglandular Syndrome type 1 (APS-1)
B-cell Expansion with Nuclear factor kappa-light-chain-enhancer of activated B cells and T-cell Anergy (BENTA) Disease
Caspase Eight Deficiency State (CEDS)
Caspase Recruitment Domain Family Member 9 (CARD9) Deficiency and Other Syndromes of Susceptibility to Candidiasis
Cartilage-hair hypoplasia
Chédiak-Higashi syndrome
Chronic Granulomatous Disease (CGD)
Common Variable Immunodeficiency (CVID)
Complement Deficiencies
Congenital Neutropenia Syndromes
Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) Deficiency
Cyclic neutropenia
DiGeorge syndrome
Dedicator Of Cytokinesis 8 (DOCK8) Deficiency
GATA-binding protein 2 (GATA2) Deficiency
Glycosylation Disorders with Immunodeficiency
Hyper-Immunoglobulin E Syndromes (HIES)
Hyper-Immunoglobulin M Syndromes
Interferon Gamma, Interleukin 12 and Interleukin 23 Deficiencies
Leukocyte Adhesion Deficiency (LAD) Types 1 and 2
Lipopolysaccharide Responsive Beige-Like Anchor Protein (LRBA) Deficiency
Phosphatidylinositol 3-kinase (PI3-Kinase) Disease
Phospholipase C gamma 2 (PLCG2) associated Antibody Deficiency and Immune Dysregulation (PLAID)
Severe Combined Immunodeficiency (SCID)
Selective Immunoglobulin A (IgA) deficiency
Signal transducer and activator of transcription 3 (STAT3) Dominant-Negative Disease
STAT3 Gain-of-Function Disease
Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome
Wiskott-Aldrich Syndrome (WAS)
X-Linked Agammaglobulinemia (XLA)
X-Linked Lymphoproliferative Disease (XLP)
X-linked magnesium transporter 1 (MAGT1) deficiency with increased susceptibility to Epstein-Barr virus (EBV) infection and N-linked glycosylation defect (XMEN) Disease
Zeta-associated protein 70 (ZAP-70) deficiency

Secondary

Malnutrition
Uncontrolled Diabetes mellitus
Chronic uremia
Genetic syndromes: trisomy 21
Immunomodulatory, immunosuppressive drug therapy: corticosteroids, calcineurin inhibitors, cytotoxic agents
Systemic lupus erythematosus
Malignancy
Active radiation therapy
Bone marrow ablation
Infectious diseases: human immunodeficiency virus (HIV) infection, Hepatitis

Additional Primary and secondary immunodeficiencies can be found at the following link.

https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/overview-of-immunodeficiency-disorders

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

72 participants in 3 patient groups, including a placebo group

Placebo (microcrystalline cellulose)

Placebo Comparator group

Description:

Placebo capsules by mouth twice daily x 5 days (5 days of placebo microcrystalline cellulose capsules)

Treatment:

Other: Placebo (microcrystalline cellulose)

Procedure: Wound management

Antibiotic x 1 day

Active Comparator group

Description:

Amoxicillin-clavulanate 875-125mg capsules by mouth twice daily x 1 day (4 days of placebo capsules) -Penicillin allergy: ciprofloxacin 500mg by mouth twice daily + clindamycin 300mg by mouth three times daily x 1 day

Treatment:

Drug: Clindamycin

Other: Placebo (microcrystalline cellulose)

Drug: Ciprofloxacin

Procedure: Wound management

Drug: Amoxicillin/clavulanate

Antibiotic x 5 days

Active Comparator group

Description:

Amoxicillin-clavulanate 875-125mg capsules by mouth twice daily x 5 days (0 days of placebo capsules) -Penicillin allergy: ciprofloxacin 500mg by mouth twice daily + clindamycin 300mg by mouth three times daily x 5 days

Treatment:

Drug: Clindamycin

Drug: Ciprofloxacin

Procedure: Wound management

Drug: Amoxicillin/clavulanate