Lyme Disease

Review here and NEJM reviews here and here. IDSA 2006 guidelines on tick borne illness here.

Transmitted by ticks of the Ixodes family, usually nymphs (see photos), this spirochete infection causes the following recognized syndromes:

1. Early localized infection: characteristic rash (erythema chronica migrans) with cleared centre, of at least 5cm diameter, in context of possible fever, chills, headache, malaise, myalgias.
   
2. Early disseminated infection: few days to weeks post infection. Additional ECM lesions in presence of musculoskeletal symptoms (60% - i.e. migratory arthritis, muscle and joint pain), neurological (15% -- i.e. facial nerve palsy, menigoencephalitis, radiculopathies) or cardiac (10% -- i.e. AV block)
3. Late disseminated infection: up to 60% untreated. Arthritis of knees and hips, occasionally a slowly progressive encephalopathy or polyradiculopathy.

Recent article on the emergence of this disease in Canada. This article has probably caused more phone calls to the ID service for 'Lyme' in the past few months than in the past few years. The article demonstrates the expansion of the territory of the Ixodes tick and the concern is that where the tick goes, the pathogen will eventually follow.

Treatment for early disease is oral doxycycline (or amoxicillin in patients whom doxycycline is contraindicated) for 14-21 days. EDIT: 10 days is sufficient

Remember: to get Lyme disease you need to be bitten by the right tick (see below), at the right time of year, in the right place in the world. The majority of consults seen outside endemic areas (or travel to) involve the wrong tick and the wrong place. In these cases Lyme serology will *not* be helpful due to the low specificity.

NB: NEJM review of 'chronic lyme disease' that is worth a read....


I found this site useful as well...

Addendum -- Death from chronic lyme treatment...

Latent Tuberculosis

From the Canadian TB standards:

Who to test for LTBI?

• Contacts of a known case
• Immigrants to Canada within the past 2 years
• Healthcare workers or those at high risk of nosocomial exposure
• Immunosuppressed patients (HIV, transplant, high dose steroids, TNF-alpha, etc.)
• Radiographic evidence of possible old TB without symptoms and no diagnosis

Diagnosis:

• Mantoux test (PPD) 5-TU intradermal injection
• Read at 48-72 hours
• Record the number of millimetres of induration (raised area, not just red) without rounding
  

False negative:

• Severe illness including active TB
• Malnutrition
• Immunosuppression (iatrogenic, HIV, etc)
• Major viral illness

False positive:

• Allergy to PPD
• Previous fully treated TB
• BCG (see below)
• Non-TB mycobacterial sensitization

Treatment:

1. Exclude active disease
2. INH 300mg PO OD x 9 months +/- Vitamin B6 25mg PO OD
   OR
   RIFAMPIN 600mg PO OD x 4 months
   

NNT~10 for reactivation in the general population. Risk reduction from ~10% to 1% lifetime of reactivation. Lower NNT in at-risk groups.

C. difficile

Previous blog here.

Some more "novel stuff":

• Case reports (poor quality really) of the use of tigecycline for the treatment of severe CDAD.
• Article discussing the use of the non-absorbable rifamycin, rifaximin, for the treatment of CDAD -- AKA the "rifaximin chaser"
  

Stenotrophomonas maltophilia

Today we saw a patient with S. maltophilia catheter related bacteremia.

Review of the microbiology of this organism here.

• Straight or slightly curved, motile gram negative rod
• Obligate aerobe, will grow best at 35 degrees
• Non-lactose fermenter, catalase positive, oxidase negative
• Will grow on blood agar and MacConkey -- and can be selected for using imipenem innoculated plates as they are carbepenem resistant organisms.

Can be found in the environment -- and in the hospital in multiple places, usually involving water. Patients who are infected are more likely to have:

• Prior antibiotic therapy
• Central venous catheters
• Neutropenia or cytotoxic chemotherapy
• ICU/Mechanical ventillation/Tracheostomy
• Malignancy or steroid use

The majority of cases are nosocomial; however, community acquired infections can occur.

Distinguishing between colonization and infection can be difficult, particularly for respiratory isolates. Bacteremia is a common presentation with an attributable mortality of up to 60%. ICU admission (APACHE more than 15), shock and thrombocytopenia are associated with mortality.

Endocarditis can occur, as can hospital acquired pneumonia, nosocomial meningitis, cellulitis and urinary tract infection.

TMP-SMX is the antimicrobial agent of choice (greater than 90% are sensitive). Combination with ticarcillin/clavulanate should be considered for serious infections. Quinolones may be a reasonable alternative in the TMP/SMX resistant or intolerant but consideration should also be given to combining them with ticarcillin/clavulinate.

Nodular Lymphangitis

This weekend we saw a case of nodular lymphangitis presenting with a chronic draining infection of the hand and ascending nodular lymphangitis. This was in the context of significant animal exposures and fish tank exposures.

Acute Respiratory Distress Syndrome

Today we saw a case of a patient with subacute progressive hypoxemic respiratory failure for which no infectious etiology could be confirmed.

Many different pathogens can cause sepsis, which in turn can be associated with ARDS. In terms of specific pathogens, the following are reported to cause ARDS (outside of the usual pneumonia --> sepsis --> ARDS):

• Bacterial
  
  • S. pneumoniae
  • Gram negative rods including Pseudomonas
  • Legionella, Chlamydophilia, Mycoplasma
  • Tuberculosis
• Viral
  
  • Influenza A (and B) particularly H5N1 but also H1N1 and seasonal
    
  • Coronavirus (SARS)
  • Varicella Zoster (in primary infections)
• Parasite
  
  • Plasmodium Falciparum

A non-infectious syndrome, Acute Interstitial Pneumonia (AIP) can mimic the features of ARDS pathophysiologically, radiographically, and on biopsy. Some studies suggest that AIP is as common as the infectious causes.

Guidelines for the management of severe sepsis (including ARDS) are available here.

Foley Catheter Related Urinary Tract Infection

Its not sexy -- but we saw a case of foley catheter related urinary tract infection. These two articles discuss this phenomenon (#1 #2)

The risk is approximately 5% per day of insertion and strategies aimed at minimizing this infection (as article above) are important to reduce cost, morbidity and mortality.

TB vs PCP

See previous blogs on TB here and PCP here. (NB the search function is behaving a little wonky this week -- known blogger issue). Article on PCP in acute seroconversion here -- it is very rare

Group B Streptoccal Bacteremia

Reviews here and here.

Also known as Streptococcus agalactiae, group B streptococcus is a pathogen that causes a variety of infectious syndromes. It colonizes the human GI tract and causes infection usually through a breach of the epithelial barriers.

In pregnant women it can cause choramnionitis and post-partum endometritis. In the neonate, it is a significant cause of neonatal sepsis and meningitis and this is why women are screened for carriage and given peri-partum antibiotics.

In the non-pregnant adult, it is commonly associated with:

• Bacteremia without focus (~40-50%)
• Skin/soft tissue infections (~20%)
  
• Pneumonia (~10-15%)
  
• Osteomyeltis or Septic Arthtitis (~10-15%)
• Other (Endocarditis, Peritonitis, Meningitis)
  

Diabetes is the most common underlying condition; however, other illnesses which likely pre-dispose to skin/soft tissue foci for bacterial entry including congestive heart failure is also a risk factor. Patients with underlying malignancy are also at increased risk.

Treatment includes a beta-lactam antibiotic (vancomycin in the penicillin allergic) pending sensitivities to other agents like the quinolones or clindamycin. GBS is universally penicillin sensitive at present. Source control is also important.

Staphylococcus Aureus Bacteremia

I direct you to previous posts here and here which discuss this entity. My often quoted articles including the ones on prognosis are available there. A new article on complications is available here.

This is a new review, which seems to be useful.

This article discusses the challenges of MRSA bacteremia. The challenges of MRSA are also covered here.

Adult Epiglotitis

Reviews here, here and JAMA case series here.

While the introduction of the Haemophilus influenzae type B vaccine has reduced the incidence in children, acute epiglotitis continues to occur in adults.

Patients present with sore throat, odynophagia , fever, dyspnea, drooling, dysphagia, foreign body sensation, and stridor.

Diagnosis can be made on the lateral neck radiograph (thumb-print sign) or on direct fiberoptic laryngoscopy.

The most common pathogens are oral flora including non-typable haemophilus species and group A streptococci. Treatment includes a third generation cephalosporin in association with close monitoring and airway management. Steroids (dexamethasone) are commonly used to decrease swelling, but the evidence for their use is actually limited.

About 40-50% will need invasive airway management (intubation, tracheostomy)

Catheter Related Bacteremia

Guidelines available here (excerpts below). Article on prevention here.

Diabetic Foot

Common presentation. Sometimes very difficult to treat. Would direct you to excellent guidelines here and to the JAMA Rational Clinical Exam Series here (related CID article here)

Dog Bite Infection

Good review on dog and cat bite infections here.


Prophylaxis: Amoxicillin-clavulinate or in penicillin allergic doxycycline + metronidazole (or clindamycin and moxifloxacin/levofloxacin).

Treatment of infection: Will require admission, surgical debridement with culture and broad spectrum antibiotics with gram negative and anerobic coverage (i.e. piperacillin-tazobactam, carbepenems, 3rd generation cephalosporin with metronidazole)

Pasturella multilocida, a gram-negative bacilli, is resistant to cephalexin and clindamycin. It is oxidase positve, indole positive, and won't grow well on MacConkey agar.

Capnocytophagia canismorsis, another fastidious gram negative rod is also oxidase and catalase positive. In patients with underlying immunodeficiency (splenectomy, cirrhosis, hypogammaglobulinemia) infections can progress to florid septic shock with multiorgan failure and DIC. It is hard to grow in the laboratory, and treatment should start early.

Vertebral Osteomyelitis

There is a review of osteomyelitis here with some images which I found useful below.

Because of the variety of causative organisms involved, a tissue diagnosis through bone biopsy is preferable to empiric treatment.

This article describes candidal vertebral osteomyelitis, which is also common in the IDU population and requires extended courses of treatment.

Necrotizing Fasciitis

Today we saw a case of necrotizing skin and soft tissue infection (not quite necrotizing fascitis) presenting in the groin area of a diabetic patient.

Patients who inject drugs or who have diabetes, obesity, or immunosuppression are at higher risk of these infections. Pain is an early presenting feature with later development of haemodynamic instability. Early changes resemble cellulitis; however, late changes include tense edema outside the area of compromised skin, pain disproportionate to appearance, skin discoloration, blisters/bullae and necrosis, and crepitus and/or subcutaneous gas.





Necrotizing fascitis (review) can be characterized based on the pathogens involved:

• Type I: Mixed aerobic and anaerobic infection. Often in diabetics. Includes Fornier's gangrene where the infection involves the fascial planes in the perineal area and in males can involve the scrotum and penis.
  
• Type II: Group A Streptococcus and MRSA
• Other organisms (below)
  

Treatment:

• Highly skilled surgical debridement and source control
• Appropriate antibiotics (in GAS penicillin G and clindamycin for Type I broad spectrum anaerobic and gram negative coverage -- i.e. piperacillin-tazobactam)
• IVIG -the case-control study on the use of IVIG in Invasive Group A Streptococcal disease is available here.
• Treatment of close contacts discussed here.
  

Endocarditis

We discussed endocarditis today. I will take this opportunity to 'show off' the search function of the blog and direct you here.

Duke Criteria:

Major Criteria

Microbiologic:

Positive blood cultures (>=2) with an organism that classically causes endocarditis (viridans group streptococci, staphylococcus aureus, enterococcus, HACEK organisms)
OR
Persistantly positive (>=3 or >=2 12h apart) for another organism

Echocardiologic:
Vegetation on valve not otherwise explainable or dehiscence of mechanical valve or abscess

OR

Clinical: *NEW* (not worsening) regurgitant murmur

Minor Criteria

• Predisposition -- known pre-existing valvular disease or IVDU
• Fever
• Evidence of vascular phenomenon -- septic emboli, mycotic aneurysm, Janeway lesions,
• Immunologic: glomerulonephritis (like this case), positive RF, roth spots, Osler nodes,
• Microbiologic: Blood culture not meeting major
• Echocardiographic not meeting major

Diagnosis: 2 Major, or 1 major 3 minor, or 5 minor

The ACC has updated guidelines on the management of valvular heart disease including endocarditis and endocarditis prophylaxis. These address the diagnostic algorithm and treatment in more detail.

Prosthetic Joint Infection

Today we discussed prosthetic joint infection (Recent review here)
UPDATE AUG 20 - NEJM Review Recently Published here.


Treatment options include:

• 2 stage revision -- removal of hardware, insertion of spacer with ~6weeks antibiotics before re-implantation. Highest chance for cure, significant morbidity
  
• 1 stage revision -- removal of hardware, debridement and re-implanataion with concomitant antibiotics. Less morbidiy, less chance of cure
  
• Debridement, Antibiotics and Retention -- chance of failure, little morbidity
  
• Palliation -- i.e. chronic suppressive antibiotics
  

We spent some time discussing debridement and retention (original JAMA article here, review here). In general this can be considered for MSSA, MRSA and CNST prosthetic joint infections provided:

• Relatively short duration of illness
• No loosening of the prosthesis
• Healthy overlying tissues
  
• Full OR debridement occurs
• The organism is susceptible to quinolones and rifampin (and the patient can tolerate both)

In general there is a two week induction with beta-lactam + rifampin or vancomycin + rifampin followed to ~ 3 months for THR and 6 months for TKR with levofloxacin or moxifloxacin with rifampin 450 PO BID. Treatment is continued past 3 (or 6) months if the CRP/ESR fails to normalize. Failure would be recurrent infection, intractable pain, loosening, drug intolerance.

Also -- here is a review of the use of combination rifampin with other antibiotics for the treatment of Staphyloccal infections.

Severe Falciparum Malaria

We discussed a case of a patient with 3% parasitemia but who had CNS symptoms compatible with cerebral malaria and mild renal failure.

In general, severe malaria is defined as a parasitemia of greater than 5% or disease associated with end-organ dysfuction (see NEJM article and table below)






















We also discussed the use of artesunate in the treatment of malaria. This Cochrane review suggests that as compared with IV quinine, artesunate reduced the risk of death (RR 0.62), cleared parasitemia faster, and had a lower risk of hypoglycemia. Consequently, it is likely currently the therapy of choice for severe malaria in non-pregnant adults.

Dosing is 2.4mg/kg given as an IV push at time 0, 12h, 24h and 48h. It is given in combination with a longer acting antimalarial such as doxycycline 100mg PO BID x 7days.

Generally fewer side effects than quinine or quinadine. Side effects include:

• GI symptoms (relatively common)
• Allergy ~1:3000
• Possible neurotoxicity manifesting as oto/vestibular toxicity (rare)

Candidemia

Today we discussed candidemia. The 2009 IDSA guidelines are available here.

In general:

• If the patient is critically ill, has recently been exposed to azoles, or the local prevalence of azole resistant candida is high initial therapy should be an echinocandin. Otherwise an azole like fluconazole would be appropriate.
  
• Line foci *must* be removed
• You should look for metastatic spread including the eyes or heart valves. Other investigations to look for osteomyelitis or septic thrombophlebitis should be based on history and clinical suspicion.
• Treatment duration varies depending on complication. In general, if there is no evidence of metastatic spread of infection treatment duration is 2 weeks after the last negative culture. There should be some clinical and microbiological follow-up to document relapse.
  

Prevention of Surgical Site Infections

Today we had a case of a post-sternotomy sternal wound infection. This led to a discussion on the prevention of surgical site infections (SSI) -- nosocomial, potentially preventable infections that lead to increased morbidity and mortality, cost, and length of stay.

Keys to prevention of SSI (SHEA guidelines here):

• Encourage smoking cessation
  
• Existing infections, distant from the surgical site should ideally be treated first
• Patient should be freshly showered either before the OR or the night before, often using chlorhexadine body wash (conflicting evidence on utility, see review here)
  
• Hair removal, if absolutely required, should be done with clippers
  
• Surgical site antimicrobial prophylaxis (SSP) should be chosen based on the local epidemiology and the type of surgery
• SSP should be administered within 1 hour of the first incision, ideally before the incision. Repeat doses should be administered based on the half life of the agents involved and the length of the case. Total duration should be less than 24 hours
  
• Maximal attention to sterile technique and the donning of sterile gloves, gowns, masks, and hats
• Avoidance of severe (more than 11.0) hyperglycemia peri-operatively
• Avoidance of intraoperative hypothermia (less evidence)
  

The article I was discussing regarding pre-operative chlorhexadine decolonization was actually older than I thought -- 2006 JAMA, available here. NNT was 16 to prevent nosocomial infection. Relatively high quality study.

Pre-operative mupirocin has not been shown to be beneficial for SSI (Canadian study here, larger study here) but may reduce nosocomial staph aureus infections.

No study has rigorously evaluated full pre-operative staph aureus decolonization with this protocol, which is used in Toronto for MRSA. I would probably choose to do this for elective surgeries for patients with known MRSA if there were no contraindications.

Infection of Cysts in Polycystic Kidney Disease

Today we were challenged by a case of a patient with PKD who had a urinary tract infection with a resistant E. Coli complicated by a presumed infected cyst.

In PKD, renal cyst infections are usually caused by E. Coli or other urinary organisms. They can be difficult to diagnose but often present with fever, abdominal pain, and elevated inflammatory markers. Cysts may enlarge or show evidence of complex septation or debris -- however, imaging is often not helpful in making the diagnosis.

Urine culture is positive in 40%, Blood in 25%, and cyst aspirates in another 12%. Medical therapy includes a relatively prolonged (3+ weeks) course of antibiotics. Usually fluoroquinolones or TMP/SMX are preferred because of cyst penetration. Beta-lactam and aminoglycoside penetration is relatively poor.

In failure of medical therapy (prolonged symptoms, fever, sepsis) or in cases where the presumed culprit cyst is greater than 5cm in diameter, percutaneous or surgical drainage is often required.

See the recently published case series here.

In our case today we elected to use high-dose ceftriaxone (since CIP/TMP-SMZ/AMP/CEF were resistant) to try and maximize intracyst concentration.