# 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, conside&#x72;**:**

* **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.\
&#xNAN;_&#x47;entamicin 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.&#x67;**. 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&#x20;**_**Chlamydia**_**&#x20;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**”:

* **M**icrocephaly vs. the macrocephaly secondary to hydrocephalus in congenital toxoplasmosis
* **M**ental **R**etardation
* **D**eafness (sensorineural) — also seen in congenital rubella
* **I**ntracranial **C**alcifications (periventricular) — vs. the intracranial calcifications distributed throughout the cortex and basal ganglia in congential toxoplasmosis
* **S**eizures (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.
