Bacterial infections

What are bacterial infections?

For an infectious agent, infectivity refers to the proportion of exposed persons who become infected. Pathogenicity refers to the proportion of infected individuals who develop clinically apparent disease. Virulence refers to the proportion of clinically apparent severe or fatal cases. The disease process may never progress to clinically apparent illness or result in illness that ranges from mild to severe or fatal. This range is called the spectrum of disease. Ultimately, the disease process ends in recovery, disability, or death (see Figure 2).

A bacterial infection is classified according to the site of infection and sometimes also the source of infection (see Figure 1). Some examples include:

• Skin infections
  • Acute bacterial skin and skin structure infection (ABSSSI)
• Lung infections
  • Community-acquired pneumonia (CAP)
    • Probably Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae)
  • Hospital-acquired/ventilator-associated pneumonia (HAP/VAP)
    • Probably S. aureus, Pseudomonas aeruginosa, Enterobacteria
    • Pseudomonas aeruginosa lives in moist hospital environments such as sinks and shower heads, and can also colonize the gut. It mainly infects vulnerable patients, such as those on ventilators, with burns or with weakened immune systems, and earlier antibiotic treatment raises the risk.
• Intra-abdominal infection (IAI)
• Blood-stream infection (BSI)
• Urinary-tract infection (UTI)

Symptoms

Periods of disease

The progression of an infectious disease can be divided into five periods, which are related to the number of pathogen particles and the severity of signs and symptoms (Figure 2). Infectious diseases can be contagious during all five of the periods of disease.

#	Period/Phase/Stage	Description
1	Incubation/latency	Pathogen replicates. No signs or symptoms.
2	Prodromal (subclinical disease)	Pathogen replicates. General signs and symptoms. The immune system is active.
3	Illness (clinical disease)	Most severe and characteristic signs and symptoms. Usual time of diagnosis is early in this period.
4	Decline	Pathogen particle-count declines. Signs and symptoms improve. Immune system possibly weakened—susceptibility to secondary infection.
5	Convalescence	Patient returns to normal function. Signs and symptoms resolve. Some permanent damage might have occurred.

Stages might overlap. The onset of symptoms marks the transition from subclinical to clinical disease.

Diagnosis

• Biomarkers not specific
  • 3 markers + white blood cell count (WBC, but unspecific)
    • C-reactive protein (CRP, comes late)
    • Procalcitonin (PCT, quicker than CRP)
    • IL-6
• Broth microdilution susceptibility testing (microbroth)
  • Accurate + expensive
• Vitek (automated susceptibility testing by turbidity)
  • Not as accurate as microbroth
• MALDI-TOF (mass spectrometry)
  • Identifies the species quickly, but does not test susceptibility

In the laboratory, bacteria are grown in broth, a liquid growth medium, or on agar plates, which hold a solid growth medium. On agar, a cell that divides again and again gives a heap of cells visible to the eye (a colony), although two cells that land on the same spot, or a clump of cells, also give a single colony [3].

A pure culture grown from a single colony is called an isolate, and it usually descends from a single bacterium. Below the species, a strain is a set of genetically similar descendants of one colony or cell, although the word is often used loosely. In classic microbiology, a subspecies is a named group of strains within one species that differ from the rest genetically or in their observable traits, such as Bacillus subtilis subsp. subtilis. In medicine and epidemiology, bacteria are also grouped by the molecules on their cell surface (antigens) into serotypes, or serovars, and different strains can share a serotype. The type strain of a species is the living culture its name is tied to, descended from the isolate used to describe the species [4]. The name of a species includes its genus, so Staphylococcus aureus is a species of the genus Staphylococcus. Species are grouped into genera, genera into families, families into orders and orders into classes, up to the domain [5].

An isolate from a patient’s sample is a clinical isolate. PK/PD studies are recommended to test several clinical isolates alongside a reference strain, kept in a culture collection such as the American Type Culture Collection (ATCC) and used throughout to show that results are reproducible [6]. In the protocol of one antibiotic trial, the index isolate is the one from the culture that qualified the patient for the trial, and repeat isolates from later samples are kept alongside it for analysis [7].

An isolate is wild type for a drug when it has no resistance to that drug gained through mutation or from other bacteria (acquired resistance) [8], so the same isolate can be wild type for one drug and resistant to another. How the MICs of wild-type isolates spread, and where the epidemiological cut-off falls, is covered under antibacterials.