"This leg is hot, doc," the ambulance medicwhistled. "Scratched the bottom of her foot three days ago. A nick.Nothing." He threw up a perplexed hand. Mrs. Anders, a 35-year-old blackwoman, brooded in her wheelchair. Vexed at the absurd injury that had landedher in the emergency room, she just wanted her leg to get better so she couldgo home to her three kids.

"Go to it," I told Kevin, my physician’s assistantstudent.

Kevin was a star, the kind of PA student who sometimes makesmedical school seem overrated.

"Get the history, examine her, then tell me your plan,"I told him, unnecessarily.

Ten minutes later he crisply read out of his little spiralnotebook, "The patient scratched the bottom of her left foot three daysago. Can’t remember what on. Yesterday it began to hurt and swell. Last nightshe felt feverish. Except for a history of depression, she has no other medicalproblems. No diabetes, no prior leg surgeries, no nothing, really. Her temp is104.6."

"Whew," I exhaled.

"On exam," he continued, the left foot and ankleare red, hot, and tender."

"Any other findings?"

"None."

"What do you think?"

"Cellulitis of the left ankle and foot. Needsantibiotics."

A superficial skin infection, cellulitis is both common andgenerally easy to treat. The usual causes, staph and strep bacteria, respond tooral antibiotics. Doctors prefer to treat both because it’s difficult,clinically, to distinguish them.

"Sounds good. Let’s take a look," I said.

The foot and ankle glowed a dusky red. But Mrs. Anders stillhad her pants on.

"How far up did you look?" I asked Kevin.

"Oops," he replied. Not far enough.

I smiled at Mrs. Anders and drew the curtain.

"We’ll need to take these off, I’m afraid."

"Okay," she answered neutrally.

We helped her slide the slacks off. And there, tracking upthe inside of her leg like a battalion of fire ants, was an inch-wide streak ofred.

I pointed: Lymphangitis. Classic sign of strep infection.The bug uses the lymphatic system like a highway. This infection has advancedwell beyond her ankle. She needs intravenous antibiotics.

"And I should have picked it up," Kevin lamented.

The lymph system is the complex network of vessels thatcarries waste products from the tissues back into the bloodstream. Thesevessels also carry foreign material to the lymph nodes to help promote animmune response against infection. The worry with strep infections in the lymphsystem is that they can linger in the vessels, causing local destruction beforethe immune system can be alerted to launch an effective defense. Alternatively,if strep passes out of the lymph system and invades the bloodstream, it cancause catastrophic illness without much local infection. In Mrs. Anders’s case,strep was on the march and we would have to hurry to head it off.

Streptococcus bacteria, the cause of everyday strep throat,is among our most ancient, tenacious, and versatile bacterial enemies. Strepstrains linger in the soil and on our skin, and their tricks are legion. Somecan incite surface infections like strep throat and erysipelas. (The worderysipelas—Greek for red skin—refers to a more severe skin infection thancellulitis.) . In other cases, they can invade lungs, heart valves, and spinalcords. A great opportunist, strep rampaged through nineteenth-century maternitywards as puerperal fever thanks to doctors who examined new mothers withunwashed hands between cases. Before penicillin, untreatable strep throatcaused lethal epidemics of rheumatic fever via an evil biochemical mimicry. Thestrep provokes an antibody response that mistakes the sufferer’s own heartmuscle and valves for the strep intruder.

Most recently, strep reared its hydra-like head asflesh-eating bacteria. Headlines hyped it as a new plague, but 2,500 years agoHippocrates described an erysipelas that led, gruesomely, to flesh, sinews, andbones falling away in large quantities. This horrifying condition is caused bystrep strains that slip into tissue following an innocuous scrape or cut. Ifthe infection is not treated, the bacteria can crank out enough enzymes andtoxins to literally dissolve flesh. Strep enzymes can dismantle connectivetissue, blood clots, and other living firewalls in its path. Strep toxinssabotage blood vessels and cell membranes, dropping blood pressure and floodingorgans with oxygen-blocking cellular sludge. So efficient and tailor-made tohumans are strep’s tools that in one of biology’s great ironies, we now use theenzyme streptokinase as a clot-buster to open clogged coronaries and save tensof thousands of heart attack victims a year.

Finally, this bacterial version of a Swiss Army knife killsbecause it is quick. Once it clears a beachhead, it can move at almost visiblespeed, as it had on Mrs. Anders’s leg. The nastier strains of strep secreteflesh-chewing toxins, and if the infection progresses, patients can suffer thehorrendous loss that Hippocrates so accurately described. The destruction offlesh is even more terrifying because it can commence without much evidence ofpoisoning on the surface of the skin.

"So what do we give her?" I asked my still-chagrinedPA student.

"Cellulitis can be caused by staph, strep . . ."

"Usually," I cut him off. "And you needantibiotics that cover both. But," I deepened my voice and harrumphed, "this isclassic, absolutely classic strep lymphangitis. Only strep behaves in such afashion. Your patient requires penicillin. And in large doses. So fire away."

In keeping with its particularities, strep, in this era ofantibiotic resistance, has remained exquisitely sensitive to that granddaddy ofantibiotics, penicillin.

"A million units?" Kevin asked.

"Her temp is over 104, the strep is galloping up herleg," I replied. "Let’s say 2.5 million."

All that remained was to call the admitting team and getMrs. Anders upstairs. I let Kevin do it.

"And emphasize to them it’s strep and she needs penicillin."

"Right."

We moved on to other patients. An hour later, I buttonholedMrs. Anders’s admitting intern, Carol Fields.

"Amazing lymphangitis, eh?" I asked. "Youwon’t see many as clear-cut as that. How much penicillin did you give?"

She squirmed.

"Our attending wants Cefazolin," she finallyadmitted. "Broader coverage."

+++

Cefazolin is distantly related to penicillin; both muck upthe bacterial cell-wall-building machinery critical to cell division.

What Cefazolin has over penicillin is its resistance tostaph’s penicillin-chewing enzyme, penicillinase. But against strep, penicillinleaves Cefazolin in the dust, clobbering the bug at concentrations of onlyten-millionths of a gram per liter. As horses, Cefazolin would play Clydesdaleto penicillin’s Thoroughbred. And in Mrs. Anders’s case, we had a lot of lostground to win back.

"But it’s classic strep," I said, flipping myhands up in supplication. I pulled out Rosen’s, the emergency medicine bible.

"See, right here, ‘streptococcal ascending cellulitis.’This is a carbon copy of your patient."

"I know, Dr. Dajer [DIE-er], but I’m only the intern."

I headed off and snagged the resident.

"Look," I began, "normally I’d agree with youon the Cefazolin for added staph coverage, but this is strep. The trivial entrywound, the lymphangitis. It all adds up. She needs pen."

"We’ll stick with the Cefazolin for now, thanks,"he replied in a tone that dripped "This is routine, it’s only strep orstaph."

Every week, medical journals plug newer and broader-spectrumantibiotics. The temptation to believe in the latest sawed-off shotgun isfueled by tens of millions of dollars in annual drug company profits. Andstrep, still quaintly sensitive to penicillin in an era of mega-resistant, armor-platedbacteria and implacable viruses, seems a pushover, a has-been you canpractically pick off with a slingshot.

"Broader isn’t deeper. Pen is the drug of choice,"I persisted.

The resident smiled stiffly. He was busy. "It’s whatour attending wants."

I gave up. I couldn’t prove it was only strep, because labcultures take two days. Moreover, medical etiquette demanded I pass the batonto the admitting team.

Next morning I sent Kevin up to check on her.

"She looks better, he reassured me. "Fever’s downto 102, and she says it hurts less."

"Ah well," I sighed. "So much for theclassics. She looked sick when she came in. I’m glad they were right."

On the second morning, Kevin needed no prompting to runupstairs. When he came back down, the look on his face chilled me to the heart.

"I don’t think she looks good," he said with anurgency I’d never heard him use before. "The medicine team says in itsnote she’s better, but her temp’s back up to 103.6 and the leg looks terrible."

+++

I sprinted up the stairs. At each landing my brain poundedwith the thought, "Christ, two days. Two days wasted." Mrs. Anders’sonly reply to my out-of-breath "How are you?" was a moan. The leg hadswollen enormously and taken on an ominous purple hue. Small, evil-looking blisterspuffed across the skin. I feared tissue necrosis, the beginning of catastrophe.

Once strep succeeds in penetrating deeper tissue layers withits cutting and liquefying enzymes, a chain reaction begins: muscle cellskilled by strep release potassium, phosphate, and other cellular by-productsthat poison adjacent muscle. Strep feasts on the remains and oozes new waves ofdeadly toxins. At that point the only hope for survival is to flay open thelimb and excise wide swaths of flesh.

But even with drastic surgery, strep can outstrip itspursuers. Patients can lose not only swaths of skin but limbs too.

Carol, the intern, sat at the nurses’ station jotting downlab results.

"Your patient is worse," I announced bluntly.

"But the resident said her white count was down and shelooked better," Carol replied.

Then she held up a lab slip and said, "Why do yousuppose her PTT is up?"

The PTT, or partial thromboplastin time, is a measure of howwell the clotting system is working: the higher the number, the poorer thefunction. The test involves taking a bit of blood, adding in a clotting factor,and measuring how long it takes for a clot to form. Mrs. Anders’s result hintedat a battle in her blood. Strep, in addition to killing tissue directly, cansecrete toxins that can wipe out kidney, lung, and coagulation function, forstarters. Now my alarm bells whooped.

"Because she’s in the early stages of toxic shock ortissue necrosis or both," I wanted to shout. Instead I said, "You areto give her 3 million units of penicillin right now and call aninfectious-disease consult. Stat."

"But I can’t do that," Carol replied. "It’sup to my attending."

"Do it and I’ll deal with your attending," I saidwith heat.

The trick to medical argument, paradoxically, is to soundabsolutely sure of yourself, though it’s a state achieved only by the deeplyignorant. I called the attending.

"Dr. Moore, this is Dr. Dajer. I admitted Mrs. Andersfrom the ER. Her leg looks much worse to me. I’d like to have the intern start high-dose penicillin and call an I.D. consult. Her PTT is up. She may be in theearly stages of toxic shock or tissue necrosis."

"But she looked better this morning," Dr. Moorestammered.

"But much worse than she did two days ago," Iinsisted.

"Shall we see what the I.D. consult says?" shetemporized.

"Yes, but we should start pen now."

"I’d rather wait." Medical convention says thatcellulitis is easily treated with Cefazolin, and Dr. Moore was sticking withconvention.

"Fine," I said, then rang off. I turned to Carol.

"Give her the penicillin. Don’t worry, I.D. will agree."

The infectious-disease specialist was somewhat startled bythe stat consult in a field that usually counts hours or days, not minutes, inthe onset of disease. But she took one look at Mrs. Anders’s leg, upped mypenicillin dose, and added Clindamycin. For strep has another trick: once ithas reproduced in large numbers, it more or less stops multiplying. At thisstage cell-wall monkey wrenches like penicillin aren’t as effective because fewnew bacteria and new cell walls are being made. Clindamycin tackles this phaseby directly inhibiting the bacteria’s protein-making life-support systems.Moreover, toxins and destructive enzymes are proteins, so Clindamycin offersthe theoretical advantage of shutting down the poison factory as well. But I.D.was so worried she called the surgeons. The surgeons ordered a CT scan.

If it showed tissue destruction, I would never forgivemyself. Any mottled or ratty-looking patches would be a sign that strep toxinswere tearing up the normally smooth and dense muscle tissue.

But the CT scan was negative. The next day Kevin and Itrooped up together. The leg still looked bad, but no worse. Mrs. Anders laywatching TV, ignoring us, as if to deny any association with that damn leg.

The following morning, Kevin came downstairs lookingworried.

"It’s bad," he intoned. "The leg has hugeblisters filled with pus. It’s like all her skin is falling off."

But I had been upstairs before him.

"No," I reassured him, "it’s not pus, justyellow inflammatory fluid, as in a blister after a burn. She’s getting better.But if you hadn’t figured out what was happening, she’d be dead now."

Kevin didn’t smile, despite the compliment. He still seemedstunned at how unforgiving a routine infection could be.

A week later I encountered the I.D. consultant.

"You know," she told me, "the medicine teamstill says the PTT was a lab error. They think she was doing fine on theCefazolin. They said it was only strep."

Strep has a long and daunting history of capitalizing onhuman inattentiveness. Where lies the pigheadedness gene, I wondered, thatdeludes each generation into dismissing the lessons nature has taught itsforebears—and at such cost?

The consultant shrugged. Kids these days. No respect.