主题：这个外科医疗术值得讨论讨论。 -- 九霄环珮

Sir—Your Sept 20 news item1 rightly

recognises the fine work pursued by

Ronald Sherman, who has specialised

in chronic wound care, frequently

under difficult circumstances.

Ronald Sherman and Skven

Thomas, and many others have carried

on with this unfashionable form of

treatment which has a fascinating

history, and which surely has a great

future. Maggot treatment became

widely accepted in the 1930s, after

publication of W S Baer’s classic work

on their use in severe chronic

osteomyelitis.2 Today’s cases may be

less dramatic than those of the 1930s,

but the basic problem of orthopaedic

sepsis is the same: the infective process

is typically localised, is generally near

the surface, and almost never resolves

spontaneously. Conventional treatment,

relying on large doses of

antibiotic or on destructive surgery, is

far from satisfactory. Maggots, in

many ways, offer an ideal solution.

Working in a typical National

Health Service orthopaedic unit, I

have, over the past five years, used the

maggots produced by Dr Steve

Thomas’ excellent facility at Bridgend,

UK. I have treated more than 50

patients during this period and can

confirm the efficacy of maggot

therapy. In 80% of appropriately

selected orthopaedic infections,

wounds healed completely or

improved substantially. I would,

therefore, find it hard to return to

maggotless orthopaedics.

An organisation is devoted to

promoting larva (maggot) therapy

and other biological treatments. The

International Biotherapy Society

was founded in 1995 by an

orthopaedic surgeon, John Church.

Details are available on the internet

at www.homestead.com/biotherapy

(accessed Oct 26, 2000).

Andrew Jarvis

9 Palmers Way, Worthing, West Sussex

BN13 3DP, UK

1 Bonn D. Maggot therapy: an alternative for

wound infection. Lancet 2000; 356: 1174.

2 Baer WS. The treatment of chronic

osteomyelitis with the maggot (larva of the

blow fly). J Bone Joint Surg 1931; 13:

438–75.

114, 139), this section focuses only on the highlights of maggot therapy history.

Some societies have recognized for centuries that the larvae of certain flies can

have beneficial effects upon the healing of infected wounds. There is evidence

that maggot therapy has been used by aboriginal tribes of Australia , the Hill

Peoples of Northern Burma , and possibly the Mayans of Central America

. Yet, the beneficial aspects of myiasis have not always been appreciated

universally.

Possibly the first written mention of human myiasis is in the Bible, where Job

complained, My body is clothed with worms and scabs, my skin is broken and festering.

Like many surgeons who followed, Ambroise Pare´ (1509–1590), chief surgeon

to Charles IX and Henri III, observed in 1557 at the battle of St. Quentin that

maggots frequently infested suppurating wounds (43). Hieronymus Fabricus (35)

also described the presence of maggots in wounds. In 1829, Napoleon’s surgeon

in chief, Baron Dominic Larrey, reported that when maggots developed in wounds

sustained in battle, they prevented the development of infection and accelerated

healing (69). The beneficial effects of wound myiasis were noted by the Confederate medical

officer Joseph Jones, quoted by Chernin :

I have frequently seen neglected wounds . . . filled with maggots . . . as far

as my experience extends, these worms only destroy dead tissues, and do

not injure specifically the well parts. I have heard surgeons affirm that a

gangrenous wound which has been thoroughly cleansed by maggots heals

more rapidly than if it had been left to itself.

According to Baer (4), the Confederate surgeon J Zacharias, may have been

the first western physician to intentionally introduce maggots into wounds for the

purpose of cleaning or debriding the wound. Baer (4) quotes Zacharias as stating:

Maggots . . . in a single day would clean a wound much better than any

agents we had at our command. . . . I am sure I saved many lives by their

use. . . .

Crile & Martin (22) also noted that soldiers whose wounds were infested with

maggots did far better than wounded soldiers not infested.

The founder of modern maggot therapy is William Baer (1872–1931), clinical

professor of orthopaedic surgery at the Johns Hopkins School of Medicine in

Maryland. During the First World War, Baer treated two wounded soldiers who

had lain overlooked on the battlefield for a week. Although they had sustained

serious injury and their wounds swarmed with maggots, Baer noted that the soldiers

had no fever, no evidence of systemic infection, and no pus; instead, they

had the ‘‘most beautiful pink granulation tissue that one can imagine.’’ Drawing

upon his wartime experiences, Baer treated four children with intractable bone

infections (osteomyelitis) at the Children’s Hospital in Baltimore (3). His initial

use of unsterilized maggots was very successful and the wounds healed within

six weeks. Encouraged by these results, Baer used the technique more widely.

However, several of his patients developed tetanus, and he concluded that ‘‘it

would be necessary to have sterile [viz. germ free] maggots’.

In the absence of any equally effective alternative for the treatment of osteomyelitis

or infected soft tissue injuries, the use of maggots spread quickly during

the 1930s, particularly in the United States where Lucilia sericata larvae were

produced by Lederle Corporation and sold for five dollars per 1000 (now

equivalent to about $100). By the mid-1930s, Robinson surveyed 947 North

American surgeons known to have employed maggot therapy (104). Of the 605

responding surgeons, 91.2 percent expressed a favorable opinion; only 4.4 percent

expressed an unfavorable view. The most common complaints raised by surveyed

practitioners were the cost of the maggots, the time and effort required to construct

the maggot dressings, and the discomfort to patients. Other than Baer’s cases of

tetanus and one case of erysipelas (141), which were thought to be associated

with the use of non-sterile larvae, no other serious adverse reactions were

reported.

The early maggot therapy literature describes the successful treatment of

chronic or acutely infected wounds, including bone infections (osteomyelitis) (9,

72, 75, 141), abscesses, carbuncles, and leg ulcers (36). Although the larvae were

unable to liquify dead bone, they did appear to cleave the pieces of dead bone

(sequestra) at their interface with normal bone, leaving behind clean healthy granulation

tissue (141). Based on clinical outcomes and wound cultures, Weil and

colleagues (141) believed that medicinal maggots treated many soft tissue infections,

including Clostridium welchii (Cl. perfringens). In addition, they reported

maggots to be of value in the management of some tumors, including two cases

of inoperable breast cancer. More recently, Bunkis et al (10) and Reames et al

(100) described the benefits of debridement and odor control resulting from accidental

myiasis of head and neck tumors. Seaquist and colleagues (111) also reported benefits from naturally occurring Phormia regina myiasis in a malignant lesion; however, this infestation was accompanied by pain.

During the 1930s, attempts to isolate the ‘‘maggot active principle’’ generated

several reports of the successful topical application of maggot extracts to promote

wound debridement and disinfection (73–75). An injected maggot extract ‘‘vaccine’’

was reportedly successful (73, 75), but was associated with significant

systemic reactions, and eventually was abandoned.

These years also marked the beginning of the antibiotic era. By 1940, sulfonamides

were already available, and Chain et al (12) had discovered the methods

for mass producing Flemming’s penicillin. By the mid-1940s, maggot therapy

nearly disappeared from use, probably because of (i) the emergence of antibiotics

as a readily available alternative to maggot therapy; (ii) the reduced incidence of

bone and soft tissue infections, as a consequence of widespread antibiotic use;

(iii) improved wound care and aseptic techniques; (iv) improved surgical techniques;

(v) the expense of medicinal maggots; (vi) the cumbersome maggot dressings;

and (vii) the unacceptability of live maggot dressings, relative to the newer

alternatives.

Subsequently, maggot therapy rarely was used, except as a last resort (64, 130).

In 1988, maggot therapy was described by some as being beneficial in modern

military and survival medicine (21); while others wrote:

. . . Fortunately maggot therapy is now relegated to a historical backwater,

of interest more for its bizarre nature than its effect on the course of medical

science . . . a therapy the demise of which no one is likely to mourn

. . . (139).

Meanwhile, an infectious diseases fellow at the University of California was

planning clinical trials of maggot therapy for treating pressure ulcers and other

chronic wounds. Preliminary evaluation of this study suggested that maggot therapy

offered several advantages over other wound treatments currently employed

(117–20). By 1995, dozens of patients with pressure ulcers, diabetic foot wounds,

and chronic leg ulcers were being treated also at the Biosurgical Research Unit

in Bridgend, South Wales (135), and at the Hadassah Hospital maggot therapy

center in Jerusalem (85). In 1996, the International Biotherapy Society was founded ‘‘to investigate and develop the use of living organisms, or their products,

in tissue repair.’’ The society is now one of the sponsors of an annual International

Conference on Biotherapy. Thus, the revival of maggot therapy is well under way.

Kathleen A. Greer • Senior Editor • Advances in Skin & Wound

Care • Ambler, PA

Last year, the Food and Drug Administration (FDA) gave

permission to market maggots as the first “live” medical

device. In a recent interview with Advances in Skin &

Wound Care, researcher Ronald Sherman, MD, MSc,

discussed how maggot therapy can help wound healing

and shared his thoughts on the future use of this age-old

therapy. Dr Sherman is Assistant Researcher, University of

California, and Director, BioTherapeutics, Education and

Research Foundation (BTER), both in Irvine, CA.

Q: How do maggots help kill bacteria and stimulate

granulation, as well as debride wounds?

A: In January 2004, the FDA gave clearance to produce and

market medical maggots for “debriding non-healing necrotic

skin and soft tissue wounds, including pressure ulcers,

venous stasis ulcers, neuropathic foot ulcers, and non-healing

traumatic or post surgical wounds.” In July 2004, our laboratory

at the University of California, Irvine, registered with the

FDA as a production site for medical maggots. The FDA has

not considered, nor approved, any claims of disinfection or

growth-promoting properties. Nevertheless, there are both

clinical and scientific studies that address the antibacterial

and growth-promoting properties of maggots.

Debridement results when the maggots release their

potent proteolytic digestive enzymes into the wound bed.

The wound bed is like a dinner table to maggots. These

enzymes gain access to the deeper necrotic tissue through

the mechanical debridement action of the maggots’

“mouth hooks”—2 probing appendages near their toothless

mouth. Mixed with these enzymes—or perhaps

directly as a result of some of these enzymes—many

microorganisms within the wound bed are killed.

Other infectious organisms are ingested by the maggots,

along with the partially digested necrotic tissue, and are

later killed within the maggot’s gut. These secretions have

been shown to stimulate cells in culture and are associated

with the rapid growth of epithelial and granulation tissue in

vivo. Wound healing effects may also be due to the apparent

increase in local perfusion and oxygenation that has

been recorded during maggot therapy.

Q: Are maggots used only in specialized wound centers?

A: Medical maggots are used today in more than 300 sites

around the country, including specialized wound centers

and tertiary care hospitals, specialized and general medical

outpatient clinics, extended care facilities, private practitioners’

offices, and even by visiting nurses who apply the maggot

dressings in patients’ homes.

Q: In appropriate cases, is maggot therapy more costeffective

for patients than traditional surgical procedures?

A: No therapy should ever be selected purely on the basis of

cost. We are discussing maggots today because of their

demonstrated efficacy, not simply their low cost. Nevertheless,

cost-effectiveness is a part of any meaningful discussion of medical care. And the low cost of maggot therapy

has often been touted as one of its major attributes. The

few studies that have addressed the issue of cost indicate

that maggot therapy is, indeed, more cost-effective than

comparable standard surgical or nonsurgical treatments.

We are not in a position to quantify the cost savings, but

we can surmise that it must be substantial, based on 2

observations. In Europe, where national, single-payer

health care is the norm, maggot therapy has become an

increasingly common practice. Approximately 30,000 maggot

treatments are administered annually in Europe. But there

has been less demand in the United States, where insurance

coverage of maggot therapy varies. In fact, the US

demand for medical-grade maggots has been too small to

support a single commercial supplier. Thus, the nonprofit

BTER Foundation is subsidizing the production and patient

care costs through donations.

The cost-effectiveness of maggot therapy is apparent to

many in the United States, however. Some hospitals tell me

they prefer to pay for maggots from their own operating

budgets to cure wounds and discharge patients faster than

to use more conventional, billable treatments. The major

expense associated with maggot therapy is the laborintensive

cost of preparing the perishable maggots. And, it

requires clinical time to secure dressings upon the wound.

Q: Do you believe maggots will be more widely used

for wound treatment in the near future?

A: The use of maggot therapy will soon increase, just as it

has in the rest of the world. In the United States, the

demand for medical maggots has increased by about 20%

per year over the past 10 years. Since the FDA ruling last

year, the demand has already doubled.

Selected References

Graninger M, Grassberger M, Galehr E, et al. Comments, opinions, and brief case reports: biosurgical

debridement facilitates healing of chronic skin ulcers. Arch Intern Med 2002;

162:1906-7.

Jukema GN, Menon AG, Bernards AT, et al. Amputation-sparing treatment by nature: “surgical”

maggots revisited. Clin Infect Dis 2002;35:1566-71.

Sherman RA. Maggot therapy for treating diabetic foot ulcers unresponsive to conventional

therapy. Diabetes Care 2003;26:446-51.

Sherman RA. Maggot vs conservative debridement therapy for the treatment of pressure

ulcers. Wound Repair Regen 2002;10:208-14.

Sherman RA, Shimoda KJ. Presurgical maggot debridement of soft tissue wounds is associated

with decreased rates of postoperative infection. Clin Infect Dis 2004;39:1067-70.

Wollina U, Liebold K, Schmidt WD, et al. Biosurgery supports granulation and debridement in

chronic wounds—clinical data and remittance spectroscopy measurement. Int J Dermatol

2002;41:635-9.