17 Infectious Disease

Empiric Antibiotics

Empiric antibiotics are administered in disease states which require intervention before culture and sensitivity results are available.

For suspected MRSA include:

• Vancomycin

• Linezolid

• Daptomycin

For suspected VRE include linezolid or daptomycin.

For extended-spectrum β-lactamase producing gram negative bacteria use a carbapenem.

For Pseudomonas consider the use of:

• Piperacillin-tazobactam

• Cefepime

• Imipenem

• Meropenem

Cellulitis

Cellulitis is most often caused by Staphylococcus aureus or group A streptococci. Simple infections can be treated with 1st-generation cephalosporins (e.g. cephalexin) or penicillinase-resistant β-lactams (e.g. dicloxacillin, nafcillin).

In diabetics, non-responders, or patients with signs of systemic toxicity/bacteremia, add vancomycin or linezolid for MRSA.

Cholecystitis

For cholecystitis, consider:

• Ampicillin/sulbactam or pipercillin/tazobactam (non-life threatening cases)

• Imipenem/cilastatin or meropenem (life threatening cases)

• Alternatives include metronidazole + 3rd generation cephalosporin, ciprofloxacin, or aztreonam

Endocarditis

For endocarditis, consider a penicillin OR vancomycin, PLUS gentamicin. In injection drug users and those with prosthetic valves, always cover for MRSA with vancomycin. Gentamicin may hasten clearing of bacteria from the blood, and provides coverage for VRE. Gentamicin should be added for patients with prosthetic valves. However, using both vancomycin and gentamicin for native valves is more recent and some sources may consider vancomycin alone sufficient for the majority of patients.

Epiglottitis

For epiglottitis (most often caused by Haemophilus influenzae or Streptococcus pneumoniae), use 10 days of ceftriaxone or cefotaxime.

Meningitis

For meningitis (ages 1 month - 50 years, Usually caused by Neisseria meningitidis or Streptococcus pneumoniae), use vancomycin and a third-generation cephalosporin (e.g. ceftriaxone or cefotaxime).

If patient is suspected of having Streptococcus pneumoniae meningitis, add steroids to the antibiotic regimen to reduce inflammation.

For meningitis (age >50) use vancomycin AND ampicillin AND a third-generation cephalosporin (ceftriaxone or cefotaxime).

Most often caused by N meningitidis, S pneumoniae, L monocytogenes, or aerobic gram-negative bacilli.

For meningitis (neonatal), use ampicillin AND an aminoglycoside (gentamicin) or a third-generation cephalosporin (cefotaxime).

Group B strep, E coli, L monocytogenes, and Klebsiella species

Cancer

Neutropenic cancer patients with fever should be stratified into high- and low- risk. High-risk patients have an anticipated prolonged neutropenia >7 days, ANC <100, and/or significant medical comorbidites. High-risk patients receive empiric IV therapy, low-risk receive oral therapy.

For high-risk patients, start with monotherapy with either IV:

• Anti-pseudomonal β-lactam (e.g. cefepime)

• Carbapenem (meropenem or imipenem-cilastatin)

• Or piperacillin-tazobactam

Add additional agents depending on clinical presentation.

For low-risk patients use oral ciprofloxacin plus amoxicillin-clavulanate.

Pharyngitis, Tonsilitis

For bacterial pharyngitis and tonsillitis, use β-lactams (e.g. amoxicillin) to reduce infection time and prevent sequelae such as rheumatic fever.

Most often caused by group A hemolytic Streptococcus

Pneumonia

If there is confusion about the type of pneumonia (typical vs. atypical), treat with azithromycin to cover Steptococcus pneumoniae, Mycoplasma pneumoniae, Legionella and Haemophilus influenza.

Typical community-acquired pneumonia in previously healthy patients is usually caused by _Streptococcus pneumoniae,_and should be treated with a β-lactam OR macrolide (e.g. azithromycin).

In patients with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes; alcoholism; asplenia; or immunosuppression; use a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin), or β-lactam AND a macrolide.

In ICU patients, use a β-lactam AND either azithromycin or a respiratory fluoroquinolone.

For atypical community-acquired pneumonia, use:

• Azithromycin, clarithromycin, or doxycycline in the outpatient setting

• Levofloxacin or moxifloxacin in the inpatient setting

Most often caused by Mycoplasma pneumoniae.

If concurrent gastrointestinal symptoms are present, consider Legionella, which can be treated with a macrolide or fluoroquinolone.

Septic Arthritis

For septic arthritis, treat based on gram stain.

For gram-positive cocci,(Staph aureus), use vancomycin.

For gram-negative cocci (Neisseria), use ceftriaxone (plus doxycycline for likely Chlamydia coinfection).

For gram-negative rods, use ceftazidime, cefepime, or piperacillin-tazobactam.

Sepsis

For adult Sepsis without a Clear Source, the first line antibiotics are piperacillin-tazobactam PLUS vancomycin.

For childhood sepsis without a clear source, use ceftriaxone PLUS ampicillin OR vancomycin.

For neonatal sepsis, use ampicillin PLUS either gentamicin (preferred) or cefotaxime; add vancomycin if concerned for MRSA.

For acute bacterial sinusitis, use amoxicillin-clavulanate.

Usually caused by Streptococcus pneumoniae

UTI

For simple urinary tract infection, use ONE of the following:

• Trimethoprim-sulfamethoxazole

• Ciprofloxacin

• Levofloxacin

• Nitrofurantoin

For pyelonephritis, use ciprofloxacin or levofloxacin.

Patients with true anaphylactoid penicillin allergies can often be treated with combinations avoiding penicillins or cephalosporins such as:

• Ciprofloxacin plus clindamycin

• Aztreonam plus vancomycin

CMV

Cytomegalovirus (CMV) is a viral infection characterized by a large intranuclear basophilic inclusion surrounded by a halo and small intracytoplasmic basophilic inclusion, often referred to as an “owl eye” inclusion.

The virus can be transmitted in the following way:

• Organ transplantation

• Blood transfusion

• Saliva

• Breast milk

• Sexual — semen, cervical secretions

• Congenital — transplacental; within birth canal during birth

Epidemiology of congenital CMV:

• #1 congenital infection in the developed world

• #1 viral cause of mental retardation in the U.S.

• #1 cause of sensorineural hearing loss

Immunocompetent patients are usually either asymptomatic or experience heterophile-negative mononucleosis (fatigue, fever, abnormal lymphocytes on peripheral smear).

Immunocompromised patients may develop GI, pulmonary, renal or adrenal disease. CMV retinitis is considered an AIDS defining illness.

CMV disease of the GI tract is most likely in HIV patients with a CD4 count <50/mm3.

Gastrointestinal manifestations of CMV infection in immunocompromised patients may include:

• CMV esophagitis (especially in AIDS patients) with linear ulceration (vs. “punched out” ulceration characteristic of HSV-1 esophagitis). This results in painful swallowing

• CMV colitis, which is seen often in CMV reactivation in immunosuppressed patients

• CMV hepatitis, which leads to granulomatous liver disease

Patients with CMV colitis present with low-grade fever, abdominal pain, unintentional weight loss, and frequent, small-volume, bloody diarrhea.

All patients diagnosed with CMV of the GI tract should have a ophthalmologic exam to rule out concurrent CMV retinitis.

Pulmonary manifestations of CMV infection in immunocompromised patients include interstitial (atypical) pneumonia.

Renal manifestations of CMV infection in immunocompromised patients involves progressive renal failure, leading to increased BUN and creatinine and a urinalysis demonstrating renal tubule cells with intranuclear inclusions.

Primary adrenal insufficiency (Addison’s disease) is associated with CMV infection in immunocompromised patients.

CMV is the most common cause of progressive lumbosacral polyradiculopathy in individuals with HIV and severe immunosuppression (CD4 <50/ul). CMV-related polyradiculopathy presents as a cauda equina syndrome with:

• Saddle anesthesia (anesthesia in perineal region)

• Bowel and/or bladder dysfunction

• Lower extremity weakness​ and numbness

In primary infection in a pregnant woman who does not have antibodies against the virus, CMV crosses the placenta and can infect the fetus, which results in congenital CMV. 90% of newborns with congenital CMV have no clinical evidence of disease as newborns.

Signs and symptoms that may be present at birth, but resolve within the first few weeks of life include:

• Thrombocytopenic purpura (“blueberry muffin” rash) — similar to the rash of congenital rubella

• Jaundice

• Hepatosplenomegaly

Signs and symptoms that can be permanent and devastating can be remembered with the mnemonic “MR DICS”:

• Microcephaly vs. the macrocephaly secondary to hydrocephalus in congenital toxoplasmosis

• Mental Retardation

• Deafness (sensorineural) — also seen in congenital rubella

• Intracranial Calcifications (periventricular) — vs. the intracranial calcifications distributed throughout the cortex and basal ganglia in congential toxoplasmosis

• Seizures (likely due to the intracranial calcifications)

CMV can be diagnosed with urinalysis, culture buffy coat (WBCs), PCR, or serology.

CMV can be diagnosed based on serology if:

• Positive for CMV specific IgM antibody

• 4 fold increase in CMV specific IgG antibody in samples obtained 2-4 weeks apart

CMV disease of the GI tract is diagnosed by endoscopy or colonoscopy with biopsy demonstrating histological evidence of the disease (large cells with characteristic eosinophilic intranuclear inclusions and basophilic intracytoplasmic inclusions).

Treatment of CMV involves IV Ganciclovir (levels of oral ganciclovir are 5-10 folds less than its IV counterpart). Ganciclovir is used for CMV prophylaxis in transplant patients.

Major adverse effects of ganciclovir are hematologic effects (ie, neutropenia, anemia, thrombocytopenia).

Foscarnet is used in Ganciclovir resistant cases. Side effects include hypocalcemia, hypokalemia, hypomagnesemia and hyperphosphatemia.