Critical Care Medicine

Infections of the central nervous system (CNS) encompass a range of potentially life-threatening infections. They often require acute management and careful monitoring in an intensive care setup. The most common causes of ICU admission due to CNS infections include acute bacterial meningitis, acute viral encephalitis, tuberculous meningitis, fungal meningitis, neurocysticercosis, abscess, and myelitis.

Involvement of the CNS may be through direct involvement or via the hematogenous route. Direct inoculation occurs via traumatic breach of the natural defenses of skin, soft tissue, and bone. Hematogenous spread may occur via arterial or venous dissemination, which breaches the blood–brain and blood–CSF barriers. Once the organism gains access to the subarachnoid space, there is proliferation due to the immune-deprived nature of the subarachnoid space.

List of etiological agents causing CNS infections

Table 8.1 List of etiological agents causing CNS infections, from Vibha, D., Garg, D. (2020). Infections of the Central Nervous System (CNS) in the ICU. In: Soneja, M., Khanna, P. (eds) Infectious Diseases in the Intensive Care Unit. Springer, Singapore.

Diagnosis

Patients with CNS infections usually present with fever, headache, and altered mental status. This triad may be seen in patients with encephalopathy due to sepsis as well. Hence, other clinical clues must be sought to establish a clinical diagnosis of meningitis, encephalitis, or cerebral abscess. Patients with meningitis may complain of neck stiffness in addition, may demonstrate signs of meningeal irritation in the form of neck stiffness, Kernig’s and Brudzinski’s signs. Chronic meningitis such as tuberculous or fungal may lead to basal exudates and entrapment of the cranial nerves. Patients with acute viral encephalitis like herpes simplex may have additionally seizures. Focal neurological signs may be found in patients with abscesses, and in these patients, signs to suggest a focus such as chronic suppurative otitis media, and sinusitis should be sought.

Differential Diagnoses

• Encephalopathy - diffuse cerebral dysfunction in the absence of infection of the central nervous system, including toxins (most commonly alcohol and illicit drugs), metabolic factors, and sepsis
• Subarachnoid Hemorrhage (SAH) - differentiating features from bacterial meningitis include severe headache at onset and the absence of fever
• Non-infectious Meningitis - drugs-induced, non-infectious inflammatory diseases like sarcoidosis, systemic lupus erythematosus (SLE), Wegener’s granulomatosis, etc.
• Acute Disseminated Encephalomyelitis (ADEM) - usually monophasic post-infectious or post-vaccinal immune-mediated demyelinating process that is a differential for viral encephalitis
• Autoimmune Encephalitis - antibody-mediated immune process predominantly affecting the limbic system, which may be paraneoplastic or non-paraneoplastic

Skin and soft tissue infections (SSTIs) encompass various infectious conditions involving the skin, subcutaneous layer, fascia, and muscle layer. Lower extremities and perineum are most commonly involved but any part of the body may be involved.

Patients with uncomplicated superficial SSTIs are treated as outpatients and are rarely encountered in intensive care settings. Surgical infections, necrotizing infections, or complicated infections with systemic features of toxemia or sepsis are of relevance in intensive care settings.

Erysipelas and Cellulitis

Erysipelas is nonpurulent bacterial infection of superficial dermis and lymphatics presenting as well-demarcated raised erythematous plaques. Cellulitis involves the deeper dermis and subcutaneous fat, and may present with or without purulence. Cellulitis and erysipelas present with local signs of inflammation, such as erythema, tenderness, lymphangitis and warmth, with or without systemic symptoms like fever, tachycardia, and raised leucocyte counts. Erysipelas and cellulitis are caused by the entry of microbes through breach in skin.

In most cases, the offending organisms are streptococci with only a small proportion of cases, mostly in open wound or previous penetrating injury, caused by S. aureus. Treatment involves antibiotic therapy targeting streptococci and MSSA, such as penicillins, first or second generation cephalosporins, or clindamycin. Antibiotics active against MRSA (vancomycin, daptomycin, linezolid) may be considered in cellulitis associated with penetrating trauma, illicit drug use, purulent drainage, or with concurrent evidence of MRSA infection elsewhere. The affected limb should be elevated to facilitate gravity drainage of edema.

Cutaneous Abscesses

Cutaneous abscesses are collections of pus in dermis and underlying subcutaneous tissue. They present as tender and erythematous fluctuant nodules with varying degree of surrounding cellulitis. It is usually of polymicrobial etiology. Treatment is incision and drainage of pus and exploration of cavity to break all loculations. Packing of the cavity with gauze may be done, although its usefulness in wound healing has not been demonstrated. Antibiotics are to be considered in the presence of systemic features of infection or in immunocompromised patients.

Although the 2014 IDSA guidelines on management of skin and soft tissue infections do not recommend routine use of antibiotic therapy as adjunct to incision and drainage of uncomplicated abscesses, multiple randomized placebo controlled trials have demonstrated improved clinical cure and/or decreased recurrences with empiric adjunctive antibiotics active against MRSA

Necrotizing Fascitis

Necrotizing fasciitis (NF) is a rapidly progressive necrotizing infection of superficial fascia of muscles and the overlying subcutaneous fat. NF is caused by an inoculum of pathogenic microorganisms through a breach in the integrity of skin in susceptible individuals, resulting in rapid spread of infection along the fascia.

As the infection spreads, the penetrating cutaneous vessels get thrombosed leading to necrosis of overlying tissue. Reported antecedent events range from major trauma, surgery to minor injuries such as insect bites and drug injections. However, a significant number of cases (15–52%) have been reported without any antecedent cause.

Necrotizing infections most commonly involve the extremities and perineum, but may involve any site. NF is difficult to diagnose due to absence of specific clinical features. The severity of pain is frequently out of proportion to physical findings.

As the disease progresses, thrombosis of cutaneous blood vessels and destruction of nerves lead to anesthesia of the skin, accompanied by features of systemic toxemia and sepsis. Fever, malaise, nausea and vomiting, diarrhea, altered mentation is followed by circulatory shock without timely intervention.

NF is an uncommon disease with an annual incidence of 0.3–5 cases per 1,00,000 in developed nations. It is a potentially fatal disease with a high mortality rate of 20–30%.

Early empirical antibiotic therapy should be broad spectrum with coverage of MRSA, gram negative bacilli, and anaerobes. Antibiotic therapy should be guided by local antibiogram. Empiric antifungal is not warranted. The current guideline published by the Infectious Diseases Society of America (IDSA) recommends vancomycin or linezolid, plus carbapenem/piperacillin-tazobactam/combination of ceftriaxone and metronidazole.

Intravenous immunoglobulin (IVIG) has been advocated as a treatment of toxic shock syndrome due to streptococcal or staphylococcal NSTIs but the evidence behind its use is lacking.

Risk Factors for NSTIs

The most common risk factors for the development of NF and other NSTIs are as follows:

• Old age
• Diabetes mellitus
• Peripheral vascular disease
• Liver cirrhosis
• IV drug abuse
• Malignancy
• Immunosuppression
• Use of NSAIDs

Tropical and emerging infectious diseases encompass a multitude of viral, bacterial, fungal and parasitic infections that are often endemic in the developing world and with the ease of international travel are no longer only a concern in these endemic countries.

Many tropical and emerging diseases are zoonotic or vector-borne. As climate change and population growth bring humans closer to animal species, the risk of spillover events and proximity to vectors (arboviruses) increases the risks of these diseases causing outbreaks and moving beyond their endemic areas.

Complications of common Tropical/Emerging infections requiring critical care

Table 3.1 Complications of common tropical infections requiring critical care, from Niyas, V.K.M., Soneja, M. (2020). Tropical Infections in ICU. In: Soneja, M., Khanna, P. (eds) Infectious Diseases in the Intensive Care Unit. Springer, Singapore.