Article, Emergency Medicine

Antibiotic prophylaxis for ED patients with simple hand lacerations: a feasibility randomized controlled trial

a b s t r a c t

Background: The benefit of antibiotic prophylaxis for simple hand lacerations (lacerations that do not involve special structures) has not been adequately studied.

Objective: To assess the feasibility of a randomized controlled trial to determine the role of antibiotic prophylaxis in emergency department (ED) patients with simple hand lacerations.

Methods: Randomized, double-blind, placebo-controlled pilot trial in 2 urban academic EDs. Adult (>=18 years old) patients with simple hand lacerations were randomized to cephalexin, 500 mg; clindamycin, 300 mg; or placebo (every 6 hours for 7 days, all in identical capsules). Outcomes: (1) feasibility determined by the number of patients who agreed to enroll and number of patients who completed follow-up, (2) infection rate (determined by 2 physicians at 10-14 days), (3) satisfaction with wound appearance (measured by a Visual analogue scale at 30 days via phone). Medians, quartiles, and percentages with 95% confidence intervals (CI) were used to present data. Groups were compared with Kruskal-Wallis and Fisher exact tests, when appropriate.

Results: Over a 5-month period, 123 patients were approached, and 78 consented to enrollment (63%; 95% CI, 55-71%). Five were lost to follow-up (5/78, 6%; 95% CI, 2%-14%). Only one patient had infection on follow-up for an infection rate of 1% (95% CI, 0.01%-8%). Patient’s satisfaction with wound appearance did not differ among the groups.

Conclusion: The findings of this pilot study support the feasibility of a randomized, double-blind, controlled trial. The low rate of infection suggests the need of a large sample size for the trial.

(C) 2014

Introduction

More than 3.7 million hand injuries are treated annually in ED throughout the United States [1]. These injuries, especially those involving the hand, deserve special care; otherwise, the consequences could have grave impact on the patients’ functional status. Therefore, management of these injuries, especially prevention of infection, is a priority.

The standard of care for managing hand lacerations is vigorous wound irrigation, debridement, and removal of foreign bodies, if indicated. Evidence supports use of Prophylactic antibiotics for hand lacerations resulting from Open fractures, Crush injuries, and animal bites [2,3]. However, the literature is undecided on the issue of Prophylactic antibiotics for simple hand lacerations (hand lacerations that do not involve special structures such as bones, tendons, vessels,

? Source of support: None.

?? Name of organization and date of assembly if the article has been presented: Poster presentation at the American College of Emergency Physicians, 2012 ACEP Research Forum.

* Corresponding author. Staten Island University Hospital 475 Seaview Avenue Department of Emergency Medicine Staten Island, NY 10305.

E-mail address: [email protected] (N. Berwald).

or nerves). A recent evidence-based review revealed that the studies that investigated this topic lack adequate power and were rife with methodological flaws [4]. Prior studies have reported a wide range of infection rates in simple hand lacerations (b 1%-12%) [5-7]. The literature is also unclear about the factors that predispose the patient to infection after a simple hand laceration. At present, the clinicians’ decision whether to prescribe antibiotics is largely based on personal experience or patient preference.

Because of the limitations of the previous studies, there is a need for a prospective, randomized, placebo-controlled trial to determine whether prophylactic antibiotics are indicated to prevent infection in simple hand lacerations. In this pilot study, we sought to assess the feasibility of a randomized controlled trial in the ED setting to examine the utility of antibiotic prophylaxis for prevention of Wound infection in ED patients with simple hand lacerations.

Methods

This is a randomized, double-blind, placebo-controlled pilot trial in 2 urban academic centers. The EDs have a combined annual census of more than 200 000. Institutional review board approval was obtained

http://dx.doi.org/10.1016/j.ajem.2014.03.043

0735-6757/(C) 2014

N. Berwald et al. / American Journal of Emergency Medicine 32 (2014) 768771 769

at both sites. Written consent was obtained from all subjects. The trial was registered on clinicaltrials.gov (NCT01155154).

A convenience sample of adult (>=18 years old) patients, with simple hand lacerations requiring repair (by sutures, staples, or tissue adhesives) were enrolled by research associates or ED physicians at both sites. Anatomically, lacerations distal to the radial carpal ligament were considered hand lacerations. The following patients were excluded:

(1) Immunocompromised patients (cancer, chemotherapy, transplant, and human immunodeficiency virus/Acquired immunodeficiency syndrome), (2) current or recent (within 2 weeks) use of any antibiotics,

(3) gross infection as determined by the treating clinician, (4) grossly contaminated wounds by dirt or other foreign substances, (5) allergy to clindamycin or cephalexin, (6) bites (eg, dog, cat, or human),

(7) crushed injuries, (8) lacerations inflicted more than 12 hours before ED visit, and (9) pregnant or breast-feeding women. Diabetics were not excluded.

Patients were randomized, using computer-generated block randomization, to 1 of 3 groups: (1) cephalexin, 500 mg; (2) clindamycin, 300 mg; or (3) placebo. All medications were prescribed every 6 hours for 7 days. Placebo was 2 g of granulated sugar in the study capsule. Capsules were prepared by the research pharmacist and stored in coded bottles. All capsules were the same color and size. Investigators, subjects, and outcome assessors were blinded to the content of the capsules and bottles. The codes revealing the content of each bottle were stored in the research pharmacy in opaque envelopes and were opened at the end of the study.

Patients were followed up at 10 to 14 days for evidence of infection and at 30 days (phone follow-up) for patient satisfaction with wound appearance, assessed using a visual analogue scale of 1 to 10 (0 for worst to 10 for best).

Outcomes

(1) Wound infection determined by (a) direCT examination by 2 ED physicians at 10 to 14 days or (b) antibiotic requirement (when

antibiotics were prescribed by a health care practitioner specifically for suspected wound infection). (2) Patient satisfaction with appearance of the wound at 30 days using a 1 to 10 visual analogue scale (1, least satisfaction; 10, most satisfaction) obtained by contacting patients via telephone. (3) Feasibility of conducting the trial determined by the percentage of subjects who agreed to enrollment in the study and the percentage of completed follow-ups (Fig.).

Data analysis

Continuous variables are reported as medians with 25% to 75% quartiles and proportions as percentages with 95% CIs. Group comparisons were performed using Kruskal-Wallis test for continuous variables and Fisher exact test for categorical data. Significance level was set at 0.05 (2-tailed). Intention-to-treat analysis was observed during group comparisons. All analyses were performed with SPSS software (version 20.0, 2011; SPSS Inc, Chicago, IL).

Results

Over a 5-month period, 123 patients were approached, and 78 consented to enrollment (consent rate, 63%; 95% CI, 55%-71%). Five patients were lost to follow-up (5/78, 6%; 95% CI, 2-14%). Three patients were noncompliant and did not complete the medication course (4%; 95% CI, 1%-11%) but they were analyzed in the same groups that they were allocated to.

The median age of the subjects was 40 years (quartiles, 29; 53), and 71% were male (n = 52). Twenty-five patients (34%) were randomized to the clindamycin group, 24 (33%) to cephalexin, and 24 (33%) to placebo. Overall, 24 patients received placebo, and 49 patients received antibiotics. Wounds were closed with sutures in 89% and with topical skin adhesive in 11%. Wound locations were finger (63%), palm (20%), dorsum (10%), and undocumented (7%) (Table).

Only one patient was found to have infection on follow-up. Therefore, the infection rate in our study was 1 of 73 (1%; 95% CI,

Patients completed follow up 73

Lost to follow up 5 (6%)

Patients approached 123

Refused enrollment 45 (37%)

Patients consented and enrolled 78 (63%)

Randomization

Placebo 24

Cephalexin 24

Clindamycin 25

Fig. Schematic chart representing the enrollment process.

770 N. Berwald et al. / American Journal of Emergency Medicine 32 (2014) 768771

0.01%-8%). The patient with the infected wound was a 62-year-old diabetic with a 3-cm laceration inflicted by a sharp metal edge. The patient had been assigned to the placebo group but on follow-up visit was diagnosed with wound infection by 2 ED attendings and was given antibiotics. The patient’s wound healed uneventfully.

Four patients (5%; 95% CI, 2%-13%) reported minor adverse events that included (diarrhea [one patient on clindamycin and one on placebo], dizziness (one patient on cephalexin), palpitation (one patient on clindamycin), and after-taste in mouth (one patient on clindamycin). No serious adverse event was reported. Median score for wound appearance satisfaction was 8 (quartiles, 9; 10) at 30 days.

Discussion

Our study was designed to pave the way for a large, randomized, control trial by assessing the feasibility of such a trial. Our results showed that, despite challenges in patient recruitment, subjects’ willingness to participate (informed consent), compliance with medication, and loss to follow-up, such a trial is feasible.

Hand injuries are common presentations in the ED, and management of these wounds is critical as outcomes impact patients’ functional status. The main concern about simple hand lacerations is preventing wound infection. Most published trials are observational studies or have focused on treatment of infections rather than preventing them. Other studies have been designed to specifically address the increased prevalence of soft tissue infections from community-associated methicillin-resistant Staphylococcus aureus [8].

Wound infection after traumatic laceration is multifactorial. Studies have associated several patient factors and wound character- istics as being associated with wound infections including patient age, history of diabetes, wound contamination, wound width/length, location of wound on the body, and time from injury to wound closure [9,10]. Without a large-scale randomized study, it would be difficult to assess the impact of these factors on wound healing vs those attributable to antibiotic prophylaxis.

There are important implications to better understanding the role of antibiotics for simple hand lacerations. There are substantial downsides of prescribing antibiotic including health care costs, Medication side effects and allergies, and Antimicrobial resistance. A delicate balance must be maintained with respect to the use of

antibiotics to improve patient outcomes while limiting the develop- ment of resistance from inappropriate overuse.

The antibiotic selection for this study was based on physician preference as determined by a survey of ED physicians that revealed cephalexin, followed by clindamycin were the most popularly prescribed prophylactic antibiotics for hand lacerations [11].

In this study, 63% of patients who were approached consented to enrollment. Considering the fact they had to agree to take medications (cephalexin or clindamycin or placebo) for 7 days (every 6 hours), this consent rate seems to be reasonable and successful. Our results also showed that only 6% of patients were lost to follow-up, and only 4% were noncompliant.

At present, the rate of wound infection for hand laceration is unknown. Prior studies have reported a wide range of infection rates for such wounds. The infection rate in our sample was very low (1%) indicating that a very large sample size would be needed to determine an accurate rate and facilitate the objectives of future studies. Assuming a 1% infection rate, power of 0.8, and ? = .05 (2-tailed), approximately 4000 patients would need to be enrolled in each arm to show a 50% reduction in the infection rate (effect size). Given our rates of enrollment, compliance, and loss to follow-up, we believe that with proper funding, conducting a large-scale, multicenter trial should be feasible. Although such a large study would have its logistic obstacles (including funding), the data generate would provide the best evidence to answer this clinically important question.

Limitations

This study used a convenience sample of patients. We anticipate that this methodology may have lead to some sampling bias. However, this was a 2-site study in which the study populations varied greatly with respect to ethnic and socioeconomic factors supporting the generalizability of our findings. It is also important to mention the potential for physician bias regarding patient enrollment. It is possible that physicians did not approach patients who they perceived would not comply with the study regimen or those that they thought would benefit from antibiotics. In addition, we did not perform a pill count to verify compliance. We relied on self-reported adherence to the regimen to measure patient compliance. The number of wound infections was too small to comment on Interrater agreement pertaining to diagnosis of wound infection or to examine the factors that could predict the outcome of infection.

Table

Comparison of baseline characteristics among the study groups

Patient/wound characteristics

Clindamycin group (n = 25)

n (%, 95% CI)

Cephalexin group (n = 24)

n (%, 95% CI)

Placebo group (n = 24)

n (%, 95% CI)

P

Agea

39 (26, 56)

42 (32, 58)

40 (29, 52)

.851

Sex (male)

15 (60%, 41%-77%)

18 (75%, 55%-88%)

19 (79%, 59%-91%)

.295

Mechanism

.455

Metal object

12 (48%)

14 (58%)

17 (71%)

Glass

6 (24%)

5 (21%)

1 (4%)

Other

6 (24%)

4 (17%)

5 (21%)

Unknown

1 (4%)

1 (4%)

0 (0%)

Length of the wounda

2 (2, 2.5)

1.5 (1.25, 2)

2 (1.5, 2.5)

.222

Wound location

.776

Finger

16 (64%)

14 (58%)

16 (67%)

Palm

6 (24%)

6 (25%)

3 (13%)

Dorsum

6 (24%)

3 (13%)

2 (8%)

Not documented

1 (4%)

1 (4%)

3 (13%)

Multiple lacerations

2 (8%, 1%-26%)

1 (4%, 0%-22%)

1 (4%, 0%-22%)

.817

Foreign body

1 (4%, 0%-21%)

0 (0%, 0%-16%)

2 (8%, 1%-27%)

.604

Contaminated wound

1 (4%, 0%-21%)

0 (0%, 0%-16%)

2 (8%, 1%-27%)

.347

Diabetes mellitus

1 (4%, 0%-21%)

3 (13%, 4%-32%)

2 (8%, 1%-27%)

.556

a Median and quartiles.

N. Berwald et al. / American Journal of Emergency Medicine 32 (2014) 768771 771

Conclusions

The results of this pilot confirm the feasibility of a randomized, double-blind, controlled trial that could shed light on the role of antibiotic prophylaxis in prevention of wound infection in patients with simple hand lacerations. In addition, our results suggest that the risk of wound infection in these patients is low, indicating the need of a large sample size for the trial.

References

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