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Infectious Diseases

  • Joseph Varon
Chapter
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Abstract

As infectious diseases are very commonly seen in the ICU, this chapter covers both typical and atypical infections found in this setting. If the patient has been transferred to the ICU after a prolonged stay in the hospital, the treatment should be focused on a nosocomial infection. This chapter emphasizes that the first thing to do is to identify the organisms causing the patients’ infection, keeping in mind frequently found organisms. Pneumonia, severe adult respiratory syndrome (SARS), sepsis, toxic shock syndrome, and infections in patients with AIDS are among the most common infectious diseases treated in the ICU. An appropriate initial empiric therapy and correct treatment once cultures and susceptibility become available are crucial for a successful treatment.

Keywords

AIDS Infectious diseases Pneumonia Sepsis Nosocomial infections Meningitis Antibiotics 

The number of infectious complications encountered in the intensive care unit (ICU) continues to increase. Patients who otherwise would have not survived in the past are now improving due to new technical advancements. However, the length of stay, as well as the large number of devices employed for this purpose, predisposes patients to difficult and often fatal infections. Clinical characteristics of patients who are treated in the ICU have evolved in recent years. Those who are immunocompromised, posttransplant, and the geriatric population are now regularly treated in the ICU with the consequent increase in morbidity, mortality, and cost.

From the infectious disease point of view, the approach to a critically ill patient who is admitted to the ICU should immediately differentiate if the patient was transferred from the floor versus if the patient was directly admitted to the ICU from the community. This constitutes a paramount parameter to categorize the etiologic agents, to understand the pathophysiology of their processes, and mostly to decide which therapeutic antimicrobial interventions are needed.

■ I. Pneumonia (Nosocomial)

  1. A.
    If the patient is transferred to the ICU after being in the hospital for several days, then treatment should address the nosocomial aspect of infection and the following important facts:
    1. 1.

      Mortality rates among these patients are 20–60 %.

       
    2. 2.

      These patients represent 15 % of all hospital deaths.

       
    3. 3.

      Successful treatment depends upon underlying disease, specific causative organisms, and timely institution of therapy.

       
     
  2. B.
    Predisposing Factors
    1. 1.

      Intubation.

       
    2. 2.

      ICU: Especially the patient who is receiving sedation.

       
    3. 3.

      Antibiotics: Broad-spectrum agents will rapidly change normal flora of the mouth and gastrointestinal (GI) tract.

       
    4. 4.

      Surgery: Especially thoracic, abdominal, or neurosurgery, which increases the risk of aspiration.

       
    5. 5.

      Chronic lung disease.

       
    6. 6.

      Advanced age.

       
    7. 7.

      Immunosuppression.

       
     
  3. C.
    Etiologic Agents
    1. 1.
      Common
      • Gram-negative bacteria such as Klebsiella sp., Escherichia coli, Pseudomonas aeruginosa, Enterobacter sp., and Acinetobacter sp.

      • Gram-positive bacteria: Staphylococcus aureus.

       
    2. 2.
      Less Common
      1. (a)

        Anaerobic mouth flora (i.e., streptococci)

         
      2. (b)

        Other gram-negative bacilli (i.e., Serratia sp., Xanthomonas sp.)

         
      3. (c)

        Haemophilus influenzae

         
      4. (d)

        Legionella sp.

         
      5. (e)

        Candida sp.

         
      6. (f)

        Aspergillus sp.

         
      7. (g)

        Influenza virus

         
      8. (h)

        Streptococcus pneumoniae

         
      9. (i)

        Miscellaneous: According to prevalent organisms in each hospital

         
      10. (j)

        Tuberculosis (TB, typical and atypical)

        Another helpful approach is to consider the likely pathogens according to the time after hospitalization the pneumonia developed. Late-onset pneumonia (after more than 5 days of hospitalization) is usually characterized with more resistant organisms.

         
       
     
  4. D.

    Clinical Manifestations. Patients in the ICU, especially those who are intubated or sedated, will not manifest the usual symptoms of pneumonia such as cough, chest pain, or dyspnea. Patients who are neutropenic cannot mount an inflammatory response, and, therefore, the sputum will not show purulent material. Subtle changes in oxygenation, fever, and clinical deterioration are clues for the diagnosis of pneumonia in intubated patients. Leukocytosis or leukopenia can be the first manifestation of occult pneumonia. In some instances, i.e., Pneumocystis pneumonia, the presence of spontaneous pneumothorax can be the first indication of pulmonary involvement. Thick, foul-smelling sputum is characteristic of anaerobic and aspiration pneumonia.

     
  5. E.
    Diagnosis
    1. 1.

      On chest X-ray, look for new or changing infiltrates.

       
    2. 2.

      Obtain sputum for Gram’s stain immediately on every patient.

       
    3. 3.

      Remember the concept of colonization versus true infection; this distinction is sometimes very difficult.

       
    4. 4.

      Be aggressive in trying to obtain diagnosis (i.e., bronchoalveolar lavage [BAL]). Transtracheal aspirates are not commonly employed.

       
    5. 5.

      Obtain other stains (i.e., acid-fast bacilli stain [AFB], Giemsa, wet prep).

       
    6. 6.

      Order serologies, if appropriate (i.e., Legionella, fungal serologies, cryptococcal antigen, CIE).

       
    7. 7.

      Remember the microbiological pattern of your hospital.

       
     
  6. F.
    Treatment Options
    1. 1.
      Empiric options most commonly utilized in the ICU
      1. (a)

        Beta-lactam plus aminoglycoside (i.e., piperacillin and tobramycin).

         
      2. (b)

        Cephalosporin plus aminoglycoside (i.e., ceftazidime and gentamicin).

         
      3. (c)

        Clindamycin plus gentamicin.

         
      4. (d)

        Clindamycin plus quinolone (i.e., ciprofloxacin).

         
      5. (e)

        Imipenem/cilastatin plus aminoglycoside.

         
      6. (f)

        Cephalosporin plus fluoroquinolone.

         
      7. (g)

        Add trimethoprim–sulfamethoxazole [TMP-SMX] if Pneumocystis carinii pneumonia is suspected.

         
      8. (h)

        Add erythromycin or azithromycin 500 mg IV qd or erythromycin 0.5–1 g IV q6 h if Legionella is suspected.

         
      9. (i)

        TMP-SMX 15–20 mg/kg/day TMP.

         
      10. (j)

        Doxycycline 100 mg IV q12 h.

         
      11. (k)

        Rifampin 300 mg IV q12 h.

         
      12. (l)

        Amphotericin B 0.6–1 mg/kg/day.

        Duration of therapy is not well defined, but most authors agree on treating gram-negative and anaerobic pneumonia for 10–21 days. Gram-positive processes are usually treated between 10 and 14 days, and atypical pneumonias receive 2 weeks of antimicrobial therapy. Candida pneumonia requires prolonged treatment with up to 1.5 g of amphotericin B as a total dose.

         
       
     
  7. G.
    Prevention
    1. 1.
      Preoperative and postoperative measures for prevention of pneumonia
      1. (a)

        Identification of high-risk patients

         
      2. (b)

        Treatment of respiratory infections, removal of respiratory secretions

         
      3. (c)

        Instruction and therapy to expand patients’ lungs (i.e., chest physiotherapy, incentive spirometry)

         
       
    2. 2.

      Proper handwashing

       
    3. 3.
      Appropriate maintenance of in-use respiratory therapy equipment
      1. (a)

        Use of sterile fluids in nebulizers

         
      2. (b)

        Proper use of single-dose and multidose medications for respiratory therapy

         
       
    4. 4.

      Proper sterilization and disinfection of reusable respiratory equipment

       
    5. 5.

      Proper suctioning of the respiratory tract

       
    6. 6.

      Protection of patients from other infected patients or staff

       
     

■ II. Community-Acquired Pneumonia

  1. A.
    Common Organisms
    1. 1.

      Streptococcus pneumoniae

       
    2. 2.

      Mycoplasma pneumoniae

       
    3. 3.

      Haemophilus influenzae

       
    4. 4.

      Klebsiella sp.

       
    5. 5.

      Respiratory viruses (influenza A and B)

       
    6. 6.

      Adenovirus, respiratory syncytial virus, parainfluenza

       
    7. 7.

      Legionella sp.

       
     
  2. B.
    Other Less Common Organisms
    1. 1.

      Pneumocystis carinii

       
    2. 2.

      Mycobacterium tuberculosis

       
    3. 3.

      Cryptococcus sp.

       
    4. 4.

      Chlamydia psittaci

       
    5. 5.

      Histoplasma sp.

       
    6. 6.

      Nocardia sp.

       
     
  3. C.
    Common Manifestations
    1. 1.

      Fever, cough, dyspnea, sputum production usually purulent but not in all cases.

       
    2. 2.

      Hypoxemia is common.

       
    3. 3.

      Anxiety.

       
    4. 4.

      Leukocytosis; also leukopenia in severe infections.

       
    5. 5.

      Pulmonary consolidation and presence or absence of pleural effusion.

       
     
  4. D.
    Uncommon Presentations in Patients Who Are 1/4
    1. 1.

      Elderly

       
    2. 2.

      Immunocompromised (especially neutropenic)

       
    3. 3.

      Posttransplantation

       
     
  5. E.
    Clinical Clues for Diagnosis
    1. 1.

      Acute onset: Bacterial, viral, aspiration, tularemia, Pneumocystis

       
    2. 2.

      Subacute onset: Viral, Legionella, Haemophilus sp., Mycoplasma, Q fever, Psittacosis, Chlamydia, Pneumocystis

       
    3. 3.

      Aerogenous route: Any segment

       
    4. 4.

      Hematogenous: Most commonly in both bases, as blood flow is preferential to these areas

       
     
  6. F.
    Associations
    1.  1.

      Birds: Psittacosis

       
    2.  2.

      Turtles: Typhoid

       
    3.  3.

      Dogs: Pasteurella multocida

       
    4.  4.

      Cattle: Q fever

       
    5.  5.

      Rabbits: Tularemia

       
    6.  6.

      Air conditioners: Legionella

       
    7.  7.

      COPD and smoking: H. Influenzae, Pseudomonas aeruginosa

       
    8.  8.

      Hides: Anthrax

       
    9.  9.

      Foreign travel: Echinococcus, paragonimiasis

       
    10. 10.

      Barracks: Neisseria meningitidis, group A Streptococcus

       
     
  7. G.
    Treatment. Empiric treatment is usually dictated by the geographical background, clinical presentation, and host status.
    • Levofloxacin 750 mg IV daily

      or

      Ceftaroline 600 mg IV q 12 h (adjust in renal dysfunction patients)

      or

    • Ceftriaxone 1 g IV plus azithromycin 500 mg IV
      1. 1.
        Streptococcus pneumonia and Haemophilus influenza
        1. (a)

          Quinolone (moxifloxacin or levofloxacin)

           
        2. (b)

          Ertapenem (1 g q24 h)

           
        3. (c)

          Ceftriaxone (1 g q24 h)

           
         
      2. 2.
        Legionella sp., Mycoplasma pneumoniae, Chlamydia pneumoniae
        1. (a)

          Moxifloxacin (400 mg IV qd)

           
        2. (b)

          Levofloxacin (500 mg IV qd)

           
        3. (c)

          Doxycycline (200 mg IV qd)

           
         
      3. 3.
        Pseudomonas aeruginosa
        1. (a)

          Meropenem (2 g IV q8 h)

           
        2. (b)

          Cefepime (2 g IV q8 h) and amikacin (1 g IV q24 h)

           
        3. (c)

          For multidrug resistant P. aeruginosa Colistin (80 mg IV q8 h)

           
         
      4. 4.
        Influenza A/B, avian influenza
        1. (a)

          Oseltamivir (Tamiflu) 75 mg PO q24 h plus rimantadine 100 mg PO.

           
        2. (b)

          Avian influenza (influenza virus type A H5N1)—influenza following close contact with infected poultry. Several outbreaks in humans have been identified in Asia: Flu-like symptoms with vague gastrointestinal complaints that rapidly progress to acute respiratory failure. Diagnosis is by hemagglutinin-specific RT-PCR for avian influenza. Treatment with antivirals should be given early, and it includes oseltamivir (150 mg), with amantadine and rimantadine.

           
         
     
  8. H.
    Complications After 72 h
    1. 1.

      Persistent fever

       
    2. 2.

      Empyema

       
    3. 3.

      Obstruction

       
    4. 4.

      Lung abscess

       
    5. 5.

      Resistant organism

       
    6. 6.

      Focus of infection

       
     

■ III. Severe Adult Respiratory Syndrome (SARS)

Term given by the World Health Organization which describes a rapidly progressive respiratory illness with documented outbreaks in China, Hong Kong, Vietnam, Singapore, and Canada. The presumable pathogen is a Coronavirus that spreads person to person via droplets, sewage, and water and potentially through human feces. It is hypothesized that bats are the primary reservoir for the disease. The mortality rate from SARS is high (up to 20 %). In severe cases, respiratory function may worsen during the second week of illness and progress to ARDS. This is a two-stage illness:
  1. 1.

    Prodrome (2–7 day): Includes fever, malaise, headache, and myalgias, and diarrhea may occur

     
  2. 2.

    Respiratory phase (8–12 day): Nonproductive cough and dyspnea that rapidly progress to respiratory failure

     

A rapid diagnosis of SARS can be made by reverse transcriptase PCR of respiratory tract, samples, and plasma early in illness.

There is no current treatment available for this illness, except for supportive care in the intensive care unit. Preventive measures against SARS are mainly focused on travel advisories to countries and cities with active outbreaks. Efforts are underway to prepare a vaccine for the prevention of SARS.

■ IV. Sepsis

  1. A.

    More than 750,000 cases of sepsis, with an associated mortality of 20–60 %, are estimated to occur annually. Despite improvements in antimicrobial therapy and supportive care, the incidence of and mortality associated with sepsis have not declined. This is, in part, a consequence of an array of medical advances that can place patients at increased risk for development of infection and, potentially, sepsis.

     
  2. B.
    Sepsis and Related Disorders
    1. 1.
      Definitions
      1. (a)

        Bacteremia: Positive blood cultures (may be transient)

         
      2. (b)
        Sepsis: Clinical evidence suggestive of infection plus signs of a systemic response to the infection (all of the following):
        1. 1.

          Tachypnea (respiration 20 breaths per minute; if patient is mechanically ventilated, minute volume 10 L/min)

           
        2. 2.

          Tachycardia (heart rate >90 beats per minute)

           
        3. 3.

          Hyperthermia or hypothermia (core or rectal temperature >38.4 °C [101 °F] or <35.6 °C [96.1 °F])

           
         
      3. (c)
        Sepsis Syndrome (may also be considered incipient septic shock in patients who later become hypotensive): Clinical diagnosis of sepsis outlined above, plus evidence of altered organ perfusion (one or more of the following):
        1. 1.

          PaO2/FiO2 no higher than 280 (in the absence of other pulmonary or cardiovascular diseases).

           
        2. 2.

          Lactate level above the upper limit of normal.

           
        3. 3.

          Oliguria (documented urine output <0.5 mL/kg body weight for at least 1 h in patients with urinary catheters in place).

           
        4. 4.

          Acute alteration in mental status.

           
        5. 5.

          Positive blood cultures are not required.

           
         
      4. (d)

        Early Septic Shock: Clinical diagnosis of sepsis syndrome as outlined above, plus hypotension (systolic blood pressure <90 mmHg or a 40-mmHg decrease below baseline systolic blood pressure) that lasts for <1 h and is responsive to conventional therapy (intravenous fluid administration or pharmacologic intervention)

         
      5. (e)

        Refractory Septic Shock: Clinical diagnosis of the sepsis syndrome outlined above, plus hypotension (systolic blood pressure <90 mmHg or a 40-mmHg decrease below baseline systolic blood pressure) that lasts for >1 h despite adequate volume resuscitation and that requires vasopressors

         
       
     
  3. C.

    Pathophysiology. Cell walls of gram-negative bacteria contain proteins, lipids, and lipopolysaccharides. Endotoxin (lipopolysaccharide) has three components: an O-specific polysaccharide, the R-core, and lipid A. Lipid A may be the major culprit in initiating the endotoxic symptoms. It is this component of endotoxin that stimulates the release of tissue necrosis factor (TNF) and can also activate the complement pathway. The sepsis syndrome is caused by endothelial damage following endotoxin-stimulated activation of neutrophils, coagulation, complement, and macrophages. Macrophages are stimulated to release TNF, interleukins, leukotrienes, thromboxane, and other cardioactive substances. Endotoxemia markedly increases the risk of myocardial depression and multiple organ failure. In patients who have positive blood cultures, those with severe endotoxemia have five times the mortality of those who do not have endotoxemia.

     
  4. D.
    Priorities in the Treatment of Sepsis
    1. (a)

      Early recognition.

       
    2. (b)

      Cardiovascular/pulmonary support.

       
    3. (c)

      Fluid resuscitation.

       
    4. (d)

      Pressor agents.

       
    5. (e)

      Empiric antibiotic therapy.

       
    6. (f)

      Other immunotherapeutic agents (investigational).

       
    7. (g)

      Corticosteroids are not effective. However, if the patient has acute adrenal insufficiency due to sepsis, steroid replacement therapy is a must.

       
    8. (h)

      Drainage of any foci of infection.

       
     
  5. E.

    Prognosis. Mortality in sepsis is a function of the severity of physiologic derangements, the duration of illness, and the number of organ system failures. These organ systems include, but are not limited to, the lungs, kidneys, and liver. When the pulmonary system becomes dysfunctional, the resultant clinical entity is known as the adult respiratory distress syndrome (ARDS). The sequence has been termed the multiple organ dysfunction syndrome (MODS). MODS is the most common cause of demise in patients who experience uncontrolled inflammation and infection.

     

■ V. Toxic Shock Syndrome

  1. A.
    Clinical Case Definition (See Table 8.1)
    Table 8.1.

    Toxic shock syndrome

    Criteria for diagnosis

     Temperature <38.9 °C

     Systolic blood pressure <90 mmHg

     Rash with subsequent desquamation, especially on palms and soles

    Involvement of >3 of following organ systems:

     Gastrointestinal: vomiting or severe diarrhea

     Muscular: severe myalgias or fivefold increase in creatine kinase

     Mucous membranes: frank hyperemia

     Renal insufficiency: serum urea nitrogen, creatinine, double of normal

     Liver: enzymes, twice upper limits of normal

     Blood: thrombocytopenia <100,000/mm3

     CNS: disorientation without focal findings

     Negative tests for leptospirosis, Rocky Mountain spotted fever, and measles

    1. 1.

      Severe febrile (38.9 °C) illness with rash (erythroderma followed by desquamation), hypotension or syncope, and multiple organ system involvement (at least four of the following: mucous membrane, GI, muscular, central nervous system [CNS], renal, hepatic, hematologic, cardiopulmonary, metabolic).

       
    2. 2.

      Hypotension: Probably due to small-vessel and capillary leakage with extravascular accumulation of fluid (edema).

       
    3. 3.

      Blood cultures are usually negative.

       
    4. 4.

      Acute episode followed by desquamation.

       
    5. 5.

      No evidence of other causes: Scarlet fever, Kawasaki’s disease, Rocky Mountain spotted fever, etc.

       
     
  2. B.
    Epidemiology and Other Clinical Features
    1. 1.

      Affects mostly young menstruating women. Tampon use, especially continuous use and Rely brand in some studies. S. aureus colonization of the vagina. Recurrence rate of 30 %. Decrease in the number of reported cases

       
    2. 2.

      Also occurs in non-menstruating women, men, and children (colonization or focal infection with S. aureus, including postoperative infections). Common occurrence after surgery. Fatality rate, 5–10 %

       
     
  3. C.

    Etiology. Exotoxin(s) of S. aureus appear to cause the disease. Recently, streptococci have been shown to cause the same syndrome.

     
  4. D.

    Differential Diagnosis. Kawasaki’s disease, scarlet fever, leptospirosis, Rocky Mountain spotted fever, measles

     
  5. E.

    Treatment. The most important treatment is volume expansion and correction of hypotension; removal of the tampon, if present, in menstruating women; debridement of wounds, etc.; and administration of antistaphylococcal antibiotics (after cultures have been obtained). Steroids have not been proven to be effective or to alter outcome.

     

■ VI. Meningitis

  1. A.
    Acute meningitis is a medical emergency that requires early recognition, rapid diagnosis, precise antimicrobial therapy, and aggressive ICU support.
    1. 1.
      Etiologic Agents
      1. (a)

        Streptococcus pneumoniae: The most common cause in adults.

         
      2. (b)

        Neisseria meningitis: Common among groups of young individuals and children.

         
      3. (c)

        Haemophilus influenzae: Common in children up to 12 years of age.

         
      4. (d)

        Staphylococcus aureus and S. epidermidis: Seen in the elderly or postoperatively (CNS shunts).

         
      5. (e)

        Listeria monocytogenes: Usually mistaken with diphtheroids or contaminants.

         
      6. (f)

        Streptococci other than S. pneumoniae: Especially group B in neonatal disease.

         
      7. (g)

        Gram-negative bacilli: After surgery or trauma.

         
      8. (h)

        Mycobacterium tuberculosis: Increasing in frequency.

         
      9. (i)

        Cryptococcus: Usually in immunosuppressed patients (i.e., those with acquired immune deficiency syndrome [AIDS] or impaired cell-mediated immunity).

         
      10. (j)

        Syphilis: Presentation variable.

         
      11. (k)

        Herpes simplex.

         
      12. (l)

        Toxoplasma: Can present as meningoencephalitis or brain abscess.

         
      13. (m)

        Naegleria: Epidemiological history is paramount.

         
      14. (n)

        Other viruses (i.e., echovirus, St. Louis, equine, and Western encephalitis).

         
       
    2. 2.
      Associations: Epidemiology and Organisms
      1. (a)

        Summer and fall: Coxsackie or echovirus; leptospira

         
      2. (b)

        Previous meningitis: S. pneumoniae

         
      3. (c)

        Alcoholism: S. pneumoniae

         
      4. (d)

        Young adults: N. meningitis

         
      5. (e)

        Elderly: S. pneumoniae, Listeria, gram-negative bacilli

         
      6. (f)

        Lymphoma: Cryptococcus sp.

         
      7. (g)

        Petechia: N. meningitidis, echovirus

         
      8. (h)

        Sinusitis: H. influenzae, S. pneumoniae, anaerobic bacteria

         
      9. (i)

        Cellulitis: Aerobic, gram-positive cocci

         
      10. (j)

        Brain abscess: Mixed flora

         
      11. (k)

        Swimming in fresh water: Amoebas

         
      12. (l)

        Other family members with meningitis: N. meningitidis

         
      13. (m)

        Water contact: Leptospira

         
      14. (n)

        Hospital acquired: Gram-negative bacilli, staphylococcus, Candida

         
      15. (o)
        Head trauma
        1. 1.

          Close fracture: S. pneumoniae, gram-negative bacilli

           
        2. 2.

          Craniotomy: Gram-negative bacilli, staphylococci

           
        3. 3.

          Cerebrospinal fluid rhinorrhea: S. pneumoniae

           
         
       
    3. 3.
      Cerebrospinal Fluid (CSF) Findings (See Table 8.2)
      Table 8.2.

      CSF findings in meningitis according to etiology

      Bacterial

      Tuberculous

      Viral

      Chronic

      Glucose >40 mg/dL (blood ratio <0.4)

      30–45 mg/dL

      20–40 mg/dL

      30–40 mg/dL

      Protein 100–500 mg/dL

      100–500 mg/dL

      50–100 mg/dL

      100–500 mg/dL

      White blood cells 1,000–10,000/cc3

      100–400/cc3

      10–1,000/cc3

      100–500/cc3

      Gram’s stain (+) 60–80 % (untreated) 40–50 % (previously treated)

      AFB smear (+) in up to 40 %

      Smears are usually negative

      Special stains needed: India ink (+)75 % AFB (+)30 %

       
    4. 4.
      Diagnostic Approach
      1. (a)

        Order antigen detection for H. influenzae, S. pneumoniae, and N. meningitidis.

         
      2. (b)

        Obtain high-volume CSF for AFB concentrate and fungal cultures (20–30 mL).

         
      3. (c)

        If CSF is normal or viruses are suspected, repeat lumbar puncture (LP) in 24–36 h.

         
      4. (d)

        Upon admission, obtain serologies for viral infections (i.e., St. Louis encephalitis, California encephalitis).

         
      5. (e)

        Obtain serologies in serum and CSF for fungal infections.

         
      6. (f)

        Polymerase chain reaction (PCR) may be helpful (especially for TB and cytomegalovirus [CMV] infections).

         
       
    5. 5.

      Treatment

      In acutely ill patients, the goal of therapy is to institute treatment before the pathologic process of inflammation can produce irreversible progression and/or death. Time is essential in this situation. Empiric therapy is instituted immediately after diagnosis is made, and it is based on the recognition of a community versus hospital and/or postoperative process. For community-acquired meningitis, usual treatment includes a third-generation cephalosporin (i.e., cefotaxime 3 g IV q6 h or ceftriaxone 2–4 g q12–24 h). Vancomycin should be added to this regimen until culture and susceptibility results are available.

       
     
  2. B.
    Pneumococcal Meningitis
    1. 1.

      Pneumococcal meningitis is still the most common cause of bacterial meningitis in adults. Underlying diseases: sickle cell disease, splenectomy and splenic dysfunction, hypogammaglobulinemia, alcoholism, head trauma (CSF fistula), and chronic pulmonary, hepatic, or renal disease.

       
    2. 2.

      Associated infections: Pneumonia, otitis, bacteremia, endocarditis, mastoiditis.

       
    3. 3.

      Therapy: Ceftriaxone 4 g/day and vancomycin 2 g/day should be given if there has been beta-lactam resistance noted locally.

       
     
  3. C.
    Haemophilus Meningitis
    1. 1.

      Underlying disease (adults): Alcoholism, compromised host defenses, head trauma.

       
    2. 2.

      Associated infections: Pneumonia, sinusitis, otitis. Secondary cases can occur in close contacts.

       
    3. 3.

      Therapy: Cefotaxime (2 g IV q6 h), ceftriaxone (2 g IV q12 h), and chloramphenicol (500 mg PO q6 h for 2 weeks) as IV to PO switch.

       
     
  4. D.
    Meningococcal Meningitis
    1. 1.

      Meningococcal meningitis is seen primarily in children, adolescents, and young adults. Secondary infection in close contacts can occur. Predisposing factors include complement defects.

       
    2. 2.

      Disseminated neisserial infection (often recurrent in persons with C5–C8 deficiency). Waterhouse–Friderichsen syndrome is an acute, often fatal, syndrome of septic shock associated with massive adrenal necrosis, associated with bacteremia due to this organism. It requires early recognition, antibiotic therapy, and especially aggressive ICU/hemodynamic support.

       
    3. 3.

      Early antimicrobial therapy is needed. Ceftriaxone 2 g IV q12 h is the preferred IV therapy; as an alternative, meropenem 2 g q8 h can be administered.

       
     
  5. E.

    Listeria Meningitis. Listeria is an important cause of bacteremia and meningitis, particularly in the elderly. Epidemiological history is important. Therapy is with ampicillin (2 g q4 h) or meropenem (excellent in vitro activity against Listeria).

     
  6. F.
    Staphylococcus aureus and Staphylococcus epidermidis. Infection with these organisms is common after neurosurgery and/or ventricular peritoneal shunt placement.
    1. 1.
      Therapy
      1. (a)

        Methicillin sensitive: Cefotaxime (3 g IV q6 h) or cefepime (2 g IV q8 h).

         
      2. (b)

        Methicillin resistant: Linezolid (600 mg IV q12 h) or vancomycin (2 g IV q12 h).

         
      3. (c)

        An infected shunt may need to be removed early in the course of therapy if the patient is not responding. Repeat LP at 2–3 days is needed in order to reach this decision (persistent growth of organisms, despite adequate therapy).

         
       
     
  7. G.
    Gram-Negative Bacilli
    1. 1.

      Infections with gram-negative bacilli are challenging to treat due to their high morbidity and mortality. Development of resistance can occur while on therapy (especially with Enterobacter sp.). Most organisms will respond to ceftriaxone, cefotaxime, or ceftazidime. For Pseudomonas aeruginosa, ceftazidime 2 g IV q8 h is the drug of choice. It should be given with gentamicin (1–2 mg/kg/8 h).

       
     
  8. H.
    Complications of Bacterial Meningitis
    1. 1.

      Brain Abscess: Usually follows trauma, contiguous infection, hematogenous dissemination.

       
    2. 2.

      Subdural Empyema: Primarily disease of the young but, in elderly, may complicate neurosurgery or subdural hematoma.

       
    3. 3.

      Epidural Abscess: Usually accompanied by focal osteomyelitis and subdural empyema.

       
    4. 4.

      All of the above are caused by mixed bacteria and usually require drainage, as well as prolonged IV antibiotic therapy.

       
     
  9. I.

    Herpes Meningitis/Encephalitis. Herpes meningitis/encephalitis is a devastating necrotizing type of encephalitis. Temporal spikes on electroencephalogram (EEG) are characteristic. Treatment is given with acyclovir 15 mg/kg q8 h (high dose) for 2 weeks. Careful attention to hydration is mandatory to avoid renal insufficiency.

     

■ VII. Infections in Patients with Aids

  1. A.
    Opportunistic infections are the most common causes of morbidity and mortality in patients with human immunodeficiency virus (HIV). Patients with CD4 cells <250 are at risk for developing severe infectious complications. Their approach is depicted in Table 8.3.
    Table 8.3.

    Approach to HIV patients with opportunistic infections

    Clinical presentation

    Common organisma

    Diagnostic procedure

    Pulmonary infiltrates

    P. carinii (PCP); tuberculosis (TB); Mycobacterium avium–intracellulare (MAI); histoplasma, aerobic bacteria, Legionella

    BAL and/or lung biopsy; appropriate serologies

    Seizures, headache, vertigo, facial palsy

    Toxoplasma, Cryptococcus MAI, herpes, CMV

    MRI, head CT, LP, and appropriate serologies

    Esophagitis

    Candida, herpes, CMV, cryptosporidium

    Endoscopy with biopsy and washings

    Diarrhea

    CMV, Cryptosporidium, Giardia, MAI, Isospora, C. difficile, Salmonella

    Stool culture (initially)b AFB stain, colonoscopy, and biopsy

    Persistent fever

    MAI, Histoplasma, TB, Cryptococcus

    CT abdomenc

    Bone marrow

    Blood cultures with special stains (AFB)

    aRemember that each one of these syndromes can be caused by noninfectious processes

    bAlso useful to obtain fecal leukocytes for diagnosis of colitis

    cPerformed when fever persists despite initial evolution

     
  2. B.
    Summary of Current Therapeutic Approaches
    1. 1.
      Pulmonary Disease
      1. (a)
        Disease Due to Pneumocystis carinii (Pneumocystis jirovecii) Pneumonia (PCP) (Table 8.4)
        Table 8.4.

        Recommended management for PCP

        Antibiotic

        Mild to moderate

        Severe (usually in ICU)

        TMP-SMX

        2–3 double-strength tabs PO tid for 14–21 days

        5 mg/kg IV q6 h for 3 weeks

        Pentamidine

        3–4 mg/kg IV–IM qd

        4 mg IV qd (once a day)

        Trimethoprim–dapsone

        Trimethoprim 100 mg PO tid dapsone 100 mg PO qid

        ?

        Clindamycin–primaquine

        Clindamycin 600 mg PO tid Primaquine 30 mg PO qid

        900 mg IV q8 h for 3 weeks

        Atovaquone

        750 mg PO bid

        For 2–3 weeks

        Trimetrexate–leucovorin

        Trimetrexate 45 mg/m2/day IV for 21 days leucovorin 30 mg/m2 IV q6 h for 10 days, and then PO q6 h for 14 days

        Same as mild to moderate

        Solu-Medrol

        Corticosteroid adjunctive therapy

        ?

        40 mg IV or (equivalent PO bid) for 5 days Wean gradually over 10 days

         
      2. (b)
        Disease Due to M. Tuberculosis
        1. 1.

          Start with at least four drugs, preferably five; INH 300 mg/day, rifampin 600 mg/day, pyrazinamide 15/kg/day, ciprofloxacin 750 mg PO bid, ethambutol 15–20 mg/kg/day.

           
        2. 2.

          If TB is sensitive to INH and/or rifampin, continue for 12–18 months (not in the ICU).

           
        3. 3.

          If TB is resistant to either or both drugs (INH and rifampin), multiple drug resistant, continue with five to six drugs, and adjust according to sensitivities. Prognosis is very poor.

           
        4. 4.

          Follow liver function tests, initially weekly and later monthly.

           
        5. 5.

          If patient cannot use PO drugs, give IV INH and rifampin (same dose) and IM streptomycin (1 g/day).

           
         
      3. (c)
        Pulmonary Disease Due To Histoplasma capsulatum
        1. 1.

          Initiate therapy with amphotericin B at 0.8–1 mg/kg/day.

           
        2. 2.

          Search for other sites of involvement (i.e., bone marrow biopsy, lumbar puncture, chest X-ray, barium enema, and small bowel series).

           
        3. 3.

          Once the patient is stable, switch to fluconazole 200 mg PO bid.

           
         
      4. (d)
        Pulmonary Disease Due To Legionella sp.
        1. 1.

          Initiate therapy with erythromycin 3–4 g IV/day.

           
        2. 2.

          If the patient is not responding, add rifampin (600 mg/day) and/or ciprofloxacin 400 mg IV q12 h.

           
         
      5. (e)
        Pulmonary Disease Due To Bacteria. Common Organisms Are:
        1. 1.

          Streptococcus pneumoniae

           
        2. 2.

          Haemophilus influenzae

           
        3. 3.

          Pseudomonas (especially if sinusitis is present)

           
         
      6. (f)
        Add Antibacterial Therapy Empirically on Admission
        1. 1.

          Ticarcillin–clavulanic acid 3.1 g IV q6 h (will also cover anaerobes in the sinuses) or piperacillin–tazobactam 3.375–4.5 g IV q6 h.

           
        2. 2.

          Cefuroxime 1.5 g IV q8 h.

           
        3. 3.

          Adjust when cultures and sensitivities become available.

           
         
      7. (g)
        Pulmonary Disease Due To M. avium–intracellulare
        1. 1.

          Ethambutol 15 mg/kg/day PO plus clarithromycin 500 mg PO q12 h or azithromycin 500 mg PO q24 h plus rifampin.

           
        2. 2.

          Treatment is given for at least 6 months after a negative sputum for MAI.

           
         
       
    2. 2.
      Enteric Pathogens in Patients with AIDS (See Table 8.5)
      Table 8.5.

      Enteric pathogens commonly seen in patients with AIDS

      Organism

      Antimicrobial agent

      Direction of therapy (days)

      G. lamblia

      Metronidazole 250 mg PO tid

      5

      E. histolytica

      Metronidazole 750 mg tid and diiodohydroxyquin 650 mg PO tid

      10

      Shigella sp.

      Fluoroquinolone IV or PO

      3–7

      C. jejuni

      Ciprofloxacin 500 mg IV q12 h

      7

      I. belli

      TMP-SMX 1 double-strength qd

      14

      CMV

      Ganciclovir 5 mg/kg IV q12 h

      30

      Herpes simplex

      Fluconazole 100 mg PO q24 h

      14

      Oral thrush

      Ketoconazole 200–400 mg/day PO

      10

      Candida esophagitis

      Fluconazole 200–400 mg/day IV

      7–10

       
    3. 3.
      CNS Infections in AIDS
      1. (a)
        Cryptococcal Meningitis
        1. 1.

          Acute: Amphotericin B 0.7–1 mg/kg/day plus 5-fluorocytosine 25 mg/kg/day until the patient is stable or improving. Then switch to fluconazole 400 mg/day PO for 3 months.

           
        2. 2.

          Maintenance: Fluconazole 200–400 mg/day PO.

           
         
      2. (b)
        Toxoplasmosis
        1. 1.

          Pyrimethamine 200 mg PO: Loading dose followed by 75 mg PO daily with folinic acid 5 mg PO daily. (No IV presentation available.)

           
        2. 2.

          Sulfadiazine 1.5 g PO q6 h; plus leucovorin 10 mg PO q24 h.

           
         
      3. (c)
        CMV (Including Retinitis)
        1. 1.

          Ganciclovir 5–10 mg/kg IV q12 h for 14 days (initial therapy)

           
        2. 2.

          Foscarnet 60 mg/kg IV q8 h for 14 days (initial therapy)

           
        3. 3.

          Lifelong suppressive therapy with valganciclovir 900 mg PO q24 h.

           
         
      4. (d)
        Herpes Simplex
        1. 1.

          Acyclovir 10–15 mg/kg IV q8 h

           
         
      5. (e)
        Syphilis
        1. 1.

          Crystalline penicillin 24 million U/day for 14 days

           
        2. 2.

          Ceftriaxone 2–4 g/day IV for 14 days

           
         
       
     
  3. C.
    Important Facts to Remember in Treating HIV-Infected Patients in the ICU
    1. 1.

      Patients may have more than one infection at the same time.

       
    2. 2.

      Blood precautions should be instituted immediately to avoid unnecessary exposure.

       
    3. 3.

      Noninfectious processes (i.e., tumors) can mimic infections.

       
    4. 4.

      Patients require a full physical examination daily, including mouth, perirectal area, and eyes.

       
    5. 5.

      Superinfections are common (i.e., fungal and resistant bacteria).

       
    6. 6.

      When fever persists, consider lumbar puncture, liver, and bone marrow biopsy.

       
    7. 7.

      Obtain CD4–CD8 counts if not recently cloned.

       
    8. 8.

      Code status needs to be established early.

       
    9. 9.

      Privacy of and respect toward patient are essential and mandatory.

       
     

■ VIII. Infections in the Immunocompromised Host

  1. A.
    The number of critically ill patients with impaired host defense mechanisms who are admitted to the ICU has dramatically increased in recent years. The knowledge and recognition of the basic deficiency enable the physician to predict the type and site of infection and allow the institution of early empiric therapy (see Tables 8.6 and 8.7).
    Table 8.6.

    Selected immunological defects and clinical presentations

    Defect

    Organism

    Manifestations

    Phagocytes/neutrophils (i.e., neutropenia)

    Gram-positive cocci

    Bacteremia

    Gram-negative bacilli

    Sepsis

    P. aeruginosa

    Tissue invasion, pneumonia, rhinocerebral and cutaneous

    Candida sp.

    Aspergillus sp.

    Mucor sp.

    Absidia sp.

    Fusarium sp.

    Complement (i.e., C5–C8 deficiency)

    Neisseria sp.

    Fulminant sepsis

    Strep. pneumoniae

    Recurrent infection

    H. influenzae

    Pneumonia

    P. aeruginosa

    Sepsis

    Brucella sp.

    Recurrent fever

    Antibody (i.e., IgA-IgG deficiency)

    Gram-positive cocci

    Pneumonia, otitis

    H. influenzae

    Meningitis

    Herpes simplex

    Encephalitis

    Giardia lamblia

    Liver disease

    Diarrhea

    Cell-mediated immunity (i.e., decrease in CD4 counts)

    Salmonella

    Diarrhea, sepsis

    Listeria sp.

    Meningitis

    Mycobacterium sp.

    Pneumonia

    Nocardia sp.

    CNS/lungs

    Cryptococcus neoformans

    Lungs

    Histoplasma capsulatum

    Mucocutaneous

    Coccidioides immitis

    Disseminated

    Herpes simplex

    Pneumonia

    Varicella zoster

    CNS/myocardium

    CMV

    P. carinii

    Strongyloides stercoralis

    Toxoplasma gondii

    Table 8.7.

    Common clinical presentations in compromised patients in the ICU

    Reason for admission

    Common pathogen

    Initial therapeutic approach

    Fever and neutropenia

    Early:

    Early empiric therapy mandatory

     Gram-negative bacilli and gram-positive cocci (usually catheter related)

    Late:

     Resistant gram-negative bacilli

     Fungi (Candida sp., Aspergillus sp., Fusarium sp., Mucor sp.)

    Sepsis: postsplenectomy

    Encapsulated bacterial organisms

    Emergency institution of antibacterial therapy

    Neurologic deterioration in patient with cell-mediated immune deficit

    Intracellular organisms

    Obtain CT, LP, and treat for bacteria and possibly for Cryptococcus

    Sepsis after solid organ transplantation

    Immediately after surgery: Common local bacteria

    Choose antibacterials according to site. Empiric therapy with extensive workup needed

    Not related to surgery: Virus, fungus, Nocardia

    Bilateral pulmonary infiltrates

    Organism depends on causative defect

    Treat empirically, and obtain BAL and biopsy (if possible)

    Diabetic ketoacidosis

    Bacterial organisms, mucormycosis, Aspergillus

    Treat for mixed bacterial infection

    AIDS

    Depends on sites of infection

    See section on AIDS

    Postoperative status and malnutrition

    Antibiotic-resistant gram-negative bacilli Group D streptococci Candida sp.

    Utilize broad-spectrum therapy

     
  2. B.

    Immunocompromised patients admitted to the ICU should be categorized according to the time of acquisition of infection.

     

Hospital-acquired infections have different etiologic agents compared to those from the community, despite having the same basic immunologic defect.

■ IX. Antimicrobials (See Table 8.8)

Table 8.8.

Selected antimicrobials commonly used in the ICU

Drug

Dose

Renal adjustment: creatinine clearance >80 50–10 <10

Comments and side effects

Aminoglycosides (i.e., gentamicin)

1–2 mg/kg IV q8 h

8–12 h

Monitor levels, renal function, and hearing

12 h

24–48 h

Broad-spectrum penicillin (i.e., piperacillin)

3–4 g IV q8 h

4–6 h

Monitor Na+ and coagulation profile

8–12 h

12–24 h

Imipenem

500 mg to 1 g

6 h

Seizures, twitching, facial palsies

12 h

24 h

Cephalosporins (i.e., ceftazidime)

2 g IV q8 h

6–12 h

Penetrates CSF well

12 h

14 h

Aztreonam

2 g IV q8 h

6–12 h

Tolerated in penicillin-allergic patients

12 h

24 h

Vancomycin

1 g IV q12 h

6–12 h

Monitor levels; interstitial nephritis

2–3 days weekly

Oxacillin

6–12 g IV

4–6 h

Infuse in at least 1 h

6–8 h

8–12 h

Acyclovir

2–3 g/day IV

8 h

Monitor WBC and renal function

12–24 h

24–48 h

Ganciclovir

5 mg/kg IV

12 h

Monitor bone marrow depression

12 h

24–48 h

Clindamycin

600–900 mg IV

8 h

Diarrhea

8 h

8 h

Chloramphenicol

3–4 g IV or PO

6 h

Monitor bone marrow function

6 h

6 h

Metronidazole

30 mg/kg/day IV or PO

6 h

Metallic taste

6 h

6 h

Amphotericin B

0.5–1 mg/kg IV

24 h

Monitor renal function

Once a day

24 h

48 h

Fluconazole

200–400 mg

12 h

Interacts with anticoagulants

q12 h IV or PO

24 h

48 h

Itraconazole

2–4 g PO

12–24 h

 

24 h

24 h

TMP-SMX

4–5 mg/kg IV (TMP) or higher

6–12 h

Monitor WBC; skin rash

12–24 h

24–48 h

Doxycycline

100–200 mg IV

12–24 h

Impairs neutrophil function

12–24 h

12–24 h

Levofloxacin

500–750 mg IV

24 h

Do not use in children

Azithromycin

500 mg IV

24 h

 

Erythromycin

1–4 g/day IV

6 h

Preferably given through central IV line

6 h

6 h

Ribavirin

Aerosolized

?

Requires special device for medication delivery

190 mg/mL at

?

12.5 L/min over

?

18 h and the rest over 6 h.

Repeat daily for 10 days

■ X. Infectious Diseases: “Pearls” for ICU Care

  1. A.

    Handwashing is the single most important procedure to prevent infection.

     
  2. B.

    Improving the nutritional status is of great importance for the outcome of infections.

     
  3. C.

    Remove bladder catheters as soon as possible.

     
  4. D.

    Complete daily physical examination is mandatory.

     
  5. E.

    Gram’s stain is the single best and least expensive test for early diagnosis of several infections (i.e., pulmonary, soft tissue, meningitis).

     
  6. F.

    Hypothermia, especially in elderly patients, suggests sepsis.

     
  7. G.

    Central catheters should be changed every 5–7 days.

     
  8. H.

    Peripheral lines should be changed every 2–3 days.

     
  9. I.

    If prolonged ICU stay is expected, early placement of subcutaneous catheters is recommended.

     
  10. J.

    Patients with high fever require special attention to fluid management.

     
  11. K.

    Antibiotics interact with many other drugs. (See previous tables.)

     
  12. L.

    Drug-induced fever is not uncommon (common agents are antibiotics, H2-antagonists, and phenytoin).

     
  13. M.

    Fever may last for several days, even when appropriate antimicrobial therapy has been instituted.

     
  14. N.

    Closely follow the clinical situation, which is more important than laboratory results.

     

■ XI. Useful Facts and Formulas

  1. A.

    Antibiotic Kinetics. The pharmacokinetics of antibiotics depends on several factors.

    The volume of distribution (VD) of an antimicrobial is calculated as
    $$ {V}_{\mathrm{D}}=\frac{A}{C_{\mathrm{p}}} $$
    where A = total amount of antibiotic in the body; Cp = antibiotic plasma concentration.
    Repetitive dosing of antibiotics depends on the principle of minimal plasma concentrations (Cmin):
    $$ {C}_{\min }=\frac{D}{\left({V}_{\mathrm{D}}\right)\left({2}^n-1\right)} $$
    where D = dose and n = dosing interval expressed in half-lives.
    The plasma concentration at steady state (Css) of an antimicrobial can be estimated utilizing the following formula:
    $$ {C}_{\mathrm{SS}}=\frac{\mathrm{D}\mathrm{ose}\ \mathrm{per}\ \mathrm{half}\ \hbox{-} \mathrm{life}}{(0.693)\left({V}_{\mathrm{D}}\right)} $$
     
  2. B.

    Antibiotic Adjustments. Renal dysfunction in critically ill patients is common.

    In those patients receiving aminoglycosides, dosage modification is required according to the aminoglycoside clearance:
    $$ \mathrm{Aminoglycoside}\ \mathrm{clearance}=\left({C}_{\mathrm{cr}}\right)(0.6)+10 $$
    where Ccr = creatinine clearance in mL/min.
    To estimate the creatinine clearance, the Cockcroft and Gault formula is utilized:
    $$ {C}_{\mathrm{cr}}\left(\mathrm{mL}/ \min \right)=\frac{\left(140-\mathrm{age}\right)\times \mathrm{weight}}{\mathrm{Cr}\times 72} $$
    where Cr = serum creatinine in mg/dL. Another modification to this formula is the Spyker and Guerrant method:
    $$ {C}_{\mathrm{cr}}\left(\mathrm{mL}/ \min \right)=\frac{\left(140-\mathrm{age}\right)\times \left(1.03-0.053\times \mathrm{C}\mathrm{r}\right)}{\mathrm{Cr}} $$
     
  3. C.
    Antibiotic Levels. Some of the clinically employed antibiotic levels are depicted in Table 8.9.
    Table 8.9.

    Selected antibiotic levels

    Antibiotic

    Level (μg/mL)

     

    Amikacin

    Peak 20–30

    Through <8

    Gentamicin

    Peak 10–20

    Through 5–10

    Chloramphenicol

    Peak 5–10

    Through <2

    Tobramycin

    Peak 5–10

    Through <2

    Vancomycin

    Peak 30–40

    Through 5–10

     
  4. D.
    Other Facts. Some of the atypical mycobacteria commonly encountered in the critical care setting are depicted in Table 8.10.
    Table 8.10.

    Selected atypical mycobacteria

    Category

    Runyon group

    Mycobacterial species

    Photochromogens

    I

    M. kansasii

    M. marinum

    Scotochromogens

    II

    M. scrofulaceum

    Nonchromogens

    III

    M. avium–intracellulare

    Rapid growers

    IV

    M. fortuitum

    M. chelonae ssp. chelonae M. chelonae ssp. abscessus M. ulcerans

     

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Joseph Varon
    • 1
    • 2
    • 3
    • 4
  1. 1.Professor of Acute and Continuing CareThe University of Texas Health Science Center at HoustonTexasUSA
  2. 2.Clinical Professor of MedicineThe University of Texas Medical Branch at GalvestonTexasUSA
  3. 3.Professor of Medicine and SurgeryUAT, UABC, USON, UPAEP, BUAP - MexicoMexicoMexico
  4. 4.President Dorrington Medical Associates, PAHoustonUSA

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