So, no disclosures for this talk, but I do have some Hand Fellowship support. So yes, the last few years I've been discussing infection in the immunocompromised patient, and it's becoming more and more challenging, as all of you have noticed. The treatment itself has not changed, but the type of organisms we're dealing with are becoming more challenging, and diagnosis and eradication is becoming more challenging as well. Early diagnosis is the key in this patient population. The number of immunocompromised hosts are increasing. Patients are living longer. Remember, the workup includes your plain x-rays, MRI for deep infections, of course labs, and then their neutrophil account, because that helps determine their ability to treat infections. The largest group of patients we deal with who are immunocompromised are diabetic patients, and that's approximately 7% of our population now. They have a high risk for hand infections, which are more severe than non-diabetic patients. And the reasons for this, the reasons they have this infection risk and have poor outcomes because of really their poor wound healing potential, oxygen delivery to tissues. They often have neuropathy. They injure themselves without realizing it, and many of them have peripheral vascular disease, and the poor vascular disease leads to poor antibiotic delivery. They also have immune deficits. Their lymphocytes don't function well. Hyperglycemia tends to enhance bacterial proliferation, and again, while the most common pathogen is Staph aureus, 50% of the infections in this population are polymicrobial and gram-negative, which sometimes are harder to treat. There's really two types of diabetic hand infections. Superficial, which is a cellulitis or superficial abscess, but the more common ones are the deep infections that include the tendon sheets, the deep spaces in bone. 50% of these patients require more than one debridement, so these are time-intensive patients when they do have an infection, and there's a high amputation rate, particularly when not diagnosed early. Treatment is more aggressive debridements than you would do in an individual who is not immunocompromised, and broad-spectrum antibiotics, because frequently these are polymicrobial infections. Necrotizing fasciitis is more common in these patients, and I'm going to discuss that in particular because that's an immunocompromised infection, or infection immunocompromised host that scares most of us, if not all of us. Prognosis is really based on the condition of this patient, because renal failure, if they have renal failure, it worsens your prognosis. Insulin dependence alone does not affect the prognosis. 100% amputation rate in diabetic renal transplant patients, so when they get infected, that's a, it's often a very difficult management situation. Gonzales, in a journal of hand surgery several years ago, wrote, noted that the increased amputation rates were associated with infections that were deep to the subcutaneous tissue in renal failure patients, infections with gram-negative bacteria, infections with anaerobic organisms, and polymicrobial infections, so, and this is a very common presentation for diabetic patients. Now, HIV patients, we see more of these individuals. They're living longer as well because of their treatment options have improved. They're predisposed to hand infections. Presentation is similar to non-HIV patients, yet the course is much more severe. Soft tissue abscesses are very common in this patient population, and they're often polymicrobial as well, which make it difficult to treat. 12% of this patient population require amputation for treatment, and these AIDS patients tend to have even more serious infections, particularly with spontaneous infections. If you have a patient that presents with spontaneous multiple septic arthritis, you should evaluate them for undiagnosed HIV or AIDS. Most common organisms are staph and strep, but herpetic, Whitlow or herpetic viral infections are very common, and they tend to be much more difficult to treat than in a non-immunocompromised patient. Necrotizing fasciitis is also more common than in a non-immunocompromised host, and treatment is, as you can imagine with all of these patients, is a very aggressive surgical debridement, culture-specific antibiotics, and obviously, all of these patients, you should get an ID consult. Organ transplant patients, at my hospital, we do a lot of organ transplants, so these are very frustrating patients to take care of as well. They all are immunocompromised because of the medications they're taking, and they get unusual infections, so you know they're infected, but it takes a while to get the organism that they have. Often, they have fungal infections or mycobacterial infections, and those of you know, mycobacterial infections tend to take a long time to grow out in culture, so they're on broad-spectrum antibiotics for a period of time. And then, this other class of patients, antitumor necrosis factor patients on these medications, I've had some terrible infections referred in when individuals who have RA who are on these medications, and serious infection rates have been reported as high as 18%. These medications predispose to wound breakdown, particularly after surgical intervention, so you have to be careful. You have to stop these medications until these patients' wounds have healed because they do have a high chance of wound breakdown and infection. Remember, these rheumatoid patients have a baseline immunologic deficiency, so they're already immunocompromised, and if they have wound breakdown problems, they have a higher risk of infection. So once again, the take-home point from this talk about immunocompromised hosts is that you've got to make the diagnosis early, treat them more aggressively than you would a non-immunocompromised patient. So there's a list of common hand infections, and most of these are covered in other talks, and really, they're not much different in terms of treatment than a non-immunocompromised host, other than being more aggressive, getting ID consult involved. You may not always get an individual who has a paronychia or a felon. You may not get an ID consult, but I urge you, an immunocompromised host, you do so. But the infections I'm going to focus on are the ones that are more common in this population and less common in the non-immunocompromised hosts, and that's atypical mycobacterium fungal, necrotizing fasciitis, osteomyelitis, and septic arthritis. So the mycobacterium infections usually present as tenosynovitis. They're pretty rare in the non-immunocompromised patient, but they can be an indolent infection. They get dactylitis or swelling of the digit. They may get synovitis of the wrist. They don't really act like a standard infection, but they do have chronic swelling, and they will obviously develop pain over time, and treatment of this is tenosynovectomy and waiting until you get appropriate cultures that identifies the organism and then treating them appropriately with a lot of medications that I'm not that comfortable prescribing. So that's when Russ comes on board and prescribes for us. These are the atypical mycobacterium is 50 percent of the musculoskeletal infections we see in this population. There's several variants of these atypical mycobacterium. They often follow puncture wounds. There's indolent inflammation. You have to have a specific biopsy stain, the zeol-Nielsen stain, and there's granulomas noted on biopsy. So the treatment for this is surgical debridement and empiric antibiotics until you have a definitive organism. There are skin lesions only in this patient population, so antibiotics alone can be used to treat these, but most of these become subcutaneous or deep infections or tenosynovitis or synovitis that require debridement and antibiotics, and the most common antibiotics, and you know, you can look at that list, and I'm sure many of you would not feel comfortable prescribing these for six months to even a year, so getting your ID colleagues involved in these patients is very important early on. Fungal infections are true pathogens or opportunists, and histoplasmosis, aspergillosis, candida, this is the type of infections I see in our organ transplant patients. The most common that we see even in the standard population is a chronic peronichia or candida but they often, subcutaneous fungal infections occur from puncture wounds, that you can have skip lesions such as sporotrichosis, which is the rose thorn injury, but the difficulty with treating these patients is that they need high dose antifungal medications and antibiotics and often these patients have severe immunocompromised and that's why they have these infections and treatment can be very challenging. Necrotizing fasciitis, I want to spend a few minutes on this diagnosis because while it's rare, it's life-threatening, and a delay in diagnosis has a negative impact and outcome. It was first described during the Confederate War, so the etiology can be from minor trauma, bites, post-op wounds, contusions, burns, penetrating injuries. The reality is, in 45% of the cases, there's no access point defined for this infection. Extremities are the most common site. If it reaches the trunk or the perineum, they're essentially dead. I mean, there's an extremely high mortality rate, so early diagnosis is critical for this, particularly if it starts in the extremities. I unfortunately see this way too much at my institution and often they're referred in and treating them is very challenging because you often have a delay in treatment. Risk factors, diabetes is the most common, but IV drug use, alcohol abuse, and really anything that leads to immunocompromised leads to this. So 50% of the cases across the country are in immunocompromised individuals if you consider diabetes as an immunocompromised state. Initial presentation is inflamed tissue that progresses rapidly to avert fasciitis and systemic life-threatening toxicity. Early diagnosis is challenging because of the paucity of skin findings frequently, and it's often misdiagnosed as a simple cellulitis. But there is a triad that you should be aware of, swelling, erythema, and inordinate pain. You look at this patient and they look sick. Your gut tells you that there's something not right, but you look at their skin and it doesn't look that bad. But they have a severe amount of pain and you're just not sure whether they're, you know, is this, it just doesn't make sense. So and pain is often precedes the skin findings by several hours. So they'll get intense pain and then they'll start getting the bullae and the eruption of the manifestations in the skin. So early diagnosis is critical. There's a rapid migration of erythema and induration of the skin despite use of IV antibiotics because remember the treatment for this is urgent surgical debridement. So just antibiotics alone is not going to solve your problem. Blister and bullae formation with hemorrhagic fluid drainage, rapid development of systemic toxicity. I have watched a patient go from appearing fairly healthy with a skin lesion to becoming hypotensive and sick within six to eight hours. And it's really a scary thing to watch. The systemic toxicity you see is acute renal failure, coagulopathy, elevated LFTs, ARDS, bacteremia. Once they hit this stage, their intensive care unit and getting to the OR is even more challenging because they're so sick. So delay in diagnosis is very common. Many patients lack clinical signs on presentation that leads to the delay as I mentioned. Bullae formation is absent in 47%. Fevers are in only 50% of these patients. So clinical diagnosis is confirmatory but it should never delay surgical intervention. If you suspect necrotizing fasciitis, don't wait on a lab result because that patient may not make it to the OR, may not make it out of your hospital. So you can draw labs and it can show azotemia, hyponatremia, thrombocytopenia. These are in later stages of the process. Often their white count is elevated and you can look at white count and sodium relationship to see if there's some changes that would be sensitive for necrotizing fasciitis. CRP, if it's greater than 16, that could be sensitive and an indicator and if you have abnormal CRP, white count, hemoglobin, sodium, creatinine and glucose, that's a 92% positive prediction for necrotizing fasciitis. Imaging may detect the gas in the soft tissues. CT scan may be beneficial. MRI shows tissue necrosis and inflammatory edema along the fascial planes. When there's no deep fascial involvement, necrotizing fasciitis can be excluded on the MRI. I always get nervous when we're sending a patient that we think has necrotizing fasciitis to an MRI scanner because you're losing critical time. MRI imaging tends to overestimate the extent of deep fascial involvement. So remember, this is a clinical diagnosis. Radiographic analysis should not delay surgical debridement. Entrop biopsy is a diagnostic benchmark. You can actually do a finger test at the bedside, make a small incision, they won't bleed and if you can slide your finger along the fascial planes and there's no tissue resistance, that's a sign, that's a pathognomonic essentially for necrotizing fasciitis. So there's about a thousand cases annually in the U.S. Mortality rates range from six to 76 percent and the reason there's that wide of a range is because of the difficulty in making an early diagnosis. If you make an early diagnosis, you'll cure this and if there's a delayed diagnosis, there's high rates of amputation and mortality, particularly if the infection reaches the trunk and perineum. Patients less than one and greater than 60 have the highest mortality rate. Most important clinical variable, I've said this again several times and I can't emphasize this enough, is time to admission until time of initial debridement. The microbiology, they're polymicrobial. Group A beta hemolytic strep and staph or the flesh eating type that's reported in the news and is the one that we see in healthy individuals, but you can get marine vibrios, there could be polymicrobial, MRSA cases have been reported as well. Treatment, diagnosis, these are patients from our institution, my institution. Surgical debridement, broad spectrum antibiotics, aggressive resuscitation, frequent evaluation with repeat surgical debridement and comprehensive nutritional support. These people need nutritional support to fight this infection and surgical debridement is the only treatment shown to increase survival. Amputation of the limb may be necessary. Evaluate the wound daily. Wound vax and once the infection is resolved, skin grafting and wound coverage. Antibiotic therapy cannot be the sole treatment. There are some high-powered guns you can use for this in addition to your surgical treatment. When it's strep infections, clinda is all is beneficial and id consult is essential if you're going to help these patients. There is some adjuvant therapies which I don't use a lot of other than the supportive care. I don't use hyperbaric oxygen. I think these have limited benefits and they haven't been supported in the literature. The last two topics are osteomyelitis of the hand and wrist. These are pyogenic infections of the bone from direct inoculation. The immunocompromised patients have a very high incidence of this compared to the general population. Traumatized bone is also susceptible to infection. The pathology is local inflammation, increased tissue pressure, low ph. What it ends up is it creates a nidus of necrotic bone or sequestrum which is a safe harbor for pathogens because of poor vascularity and drug penetration. If you have a nidus, it's very hard to treat this without surgical intervention. If an infected sequestrum is present, non-surgical care is unlikely to be successful. Osteomyelitis in many circumstances can be treated with antibiotics only if there is not a sequestrum. If you have hardware, this is an additional protection to pathogens because there's a biofilm that's around the hardware and you really can't successfully treat osteomyelitis when you have hardware present. Ultimately, the hardware has to be removed if you're going to cure osteomyelitis in this patient population. However, we have to balance the healing and loss of stability that's provided by the hardware if it's still providing stability. Often we treat through the infection until the fracture heals and then remove the hardware and treat the osteomyelitis. Diagnosis can be challenging at times. ESR and CRP are elevated, but they're better for monitoring therapy and not for making the diagnosis. MRI and bone scan do have some variable sensitivity and specificity. The gold standard is bone biopsy with positive cultures. Antibiotics are ideally delayed until cultures are obtained and it's a combined surgical and medical approach for the best outcome. ID consult is recommended and surgical debridement. Remove hardware if you can would be the ideal scenario. Once your causative organism is identified, start your specific therapy and you need several weeks of therapy and often they require PO antibiotics which have good bioavailability. Septic arthritis has a much lower prevalence in the upper extremity except in the case of immunocompromised patients. They have more upper extremity infections. STAF is the most common, but as a theme here, immunocompromised patients have polymicrobial infections which make them difficult to treat. Gonococcal infections are seen in the younger patient population who are sexually active, but they still tend to be rarer in the upper extremity. MRSA prevalence is increasing in septic arthritis, 17% in upper extremity joint septus, and the comorbidities for upper extremity MRSA infections is, as you can imagine, are immunocompromised hosts. Diagnosis, early diagnosis is critical. Physical exam and joint aspiration, ESNR, CRP are elevated and are not specific. Serum white count is not helpful. A white count of 50k and 50,000 in an aspirate used to be the traditional number, but it's not very sensitive as a diagnostic tool. Only 64% of patients with STAF aureus had an aspirate of greater than 50,000 white cells. There's a recent study that shows a correlation of aspirate of greater than 85% PMNs confirmed septic arthritis in 96% of cases. So urgent open or arthroscopic IND with empiric antibiotics and then pathogen specific antibiotics is the treatment. Delay in treatment is actually very problematic because you get irreversible chondrolysis within 72 hours. Arthroscopy of the wrist and elbow are treatment options with limited support in the literature. Mayo has a report of 36 cases of septic arthritis of the wrist and they had good results. Fewer operations compared to open treatment, shorter hospital stays, and effective in treating isolated septic wrist arthritis. But remember, these immunocompromised hosts tend to have multiple septic joints at the same time, and if you have a patient like that, please have them evaluated systemically for the reasons for that. They may have an immunocompromised process that we're not aware of. So thank you very much. Sorry, it's a lot of information, but I hope it was helpful. I'll be around for questions afterwards.

infection

immunocompromised patients

hand infections

diabetic patients

HIV patients

organ transplant patients