Antibiotic Therapy: Diagnosis, Synergistic Activity, Prevention of Resistance, Factors and Types of Therapies

The problem of antimicrobial resistance to antibiotics has led to antibiotic therapy to focus on the use of antibiotics.

In a way that ensures not only a favorable effect for the individual patient, but also the minimization of the subsequent antimicrobial resistance.

Although adequate antibiotic therapy may generate resistance, inadequate therapy can also have adverse effects on bacterial ecology.

To achieve adequate therapy, treatment must be initiated correctly, using microbiological data faithfully and subsequent evaluations.

Until you achieve an adequate response that may involve decreasing therapy or even interrupting it.

Precise diagnosis

The diagnosis of the infectious disease is achieved by determining the site of infection, define the host: Immunocompromised, diabetic, elderly among others and establish, when possible, a microbiological diagnosis.

It is essential to isolate the pathogen in serious infections, mainly in situations that may require prolonged therapy, such as endocarditis , septic arthritis or meningitis.

Similarly, when a patient does not present favorable results to the chosen antimicrobial therapy, additional studies are required to determine the agent or exclude noninfectious diagnoses.

To optimize the diagnosis it must be ensured that the samples for the east are obtained and processed properly.

The microbiological diagnosis is based on bacterial or fungal cultures or serological tests, it is possible to make an accurate diagnosis, because it can be inferred from the clinical presentation as a cellulitis.

This is caused by streptococci or staphylococci, and an antibacterial treatment can be administered without the need for culture.

The first step to perform an antibiotic therapy is a specific diagnosis, whether it is a tentative clinical diagnosis or not.

Moment of the start

The time to start therapy should correspond to the urgency of the situation.

In patients with septic shock , febrile neutropenic patients and patients with bacterial meningitis, empirical therapy is started immediately, simultaneously with the collection of diagnostic samples.

In more stable clinical conditions, antibiotic therapy should be initiated deliberately after the appropriate samples have been collected and the results obtained.

With this principle therapies are initiated in cases of subacute bacterial endocarditis and osteomyelitis , vertebral discitis, in which the administration of antibiotics is delayed until the results of the blood cultures, aspiration of the infected intervertebral disc space or bone biopsy samples.

The premature initiation of antimicrobial therapy in these circumstances can suppress bacterial growth and impede the opportunity to establish a successful microbiological diagnosis.

Empirical or definitive antibiotic therapy

Microbiological results may be available 24 to 72 hours after the sample is taken, so the initial therapy for the infection is usually empirical and guided by the clinical history.

A common approach is to use broad spectrum antimicrobial agents or combinations as initial empirical therapy, with the intention of covering multiple potential pathogens that are commonly associated with a specific clinical symptom.

When the results of microbiology have identified the pathogen and the antimicrobial susceptibility data are available, the spectrum of antibiotics should be reduced.

This is a very important factor in antibiotic therapy because it reduces the toxicity and prevents the emergence of resistance of microbes in the body.

Bacteriostatic and bactericidal therapy

Bactericidal drugs cause death and alteration of the bacterial cell, include drugs that act mainly on the cell wall, cell membrane or bacterial DNA.

Bacteriostatic agents inhibit bacterial replication without killing the organism.

Most bacteriostatic drugs act by inhibiting protein synthesis.

This distinction is not absolute, since some agents that are bactericidal against certain organisms can only be bacteriostatic against others and vice versa.

In the case of serious infections such as endocarditis and meningitis, bactericidal agents are preferred for rapid healing.

Use of antimicrobial combinations

Antimicrobial therapy with a single agent is generally preferred, but there are cases in which a combination of 2 or more antimicrobial agents is recommended, as in the case of tuberculosis .

Synergistic activity

The synergy between antimicrobial agents results in the fact that the combined effect of agents is greater than the sum of their independent activities when measured separately.

The combination of certain β-lactams and aminoglycosides shows a synergistic activity against a wide variety of gram-positive and gram-negative bacteria, is used in the treatment of serious infections, for which rapid death is essential.

In the case of certain streptococci, synergistic combinations can also be used that more rapidly eliminate the infecting microorganism and shorten the course of antimicrobial therapy.

Prevent resistance

The use of a combination therapy provides a greater possibility that at least one drug is effective, thus preventing a resistant mutant population from emerging as a dominant strain and causing a therapeutic failure.

This principle is based on the use of combined pharmacotherapy for the treatment of infections such as tuberculosis and the human immunodeficiency virus ( HIV ).

Since it is likely that the duration of treatment is prolonged, and resistance can arise with relative ease, coupled with the fact that in these cases the therapeutic agents are limited.

Factors of the host

Although it is useful for physicians to become familiar with some specific antimicrobial agents, a general approach is not appropriate in the selection of antimicrobials, and several factors of the host should be taken into account, such as:

Kidney and liver function

Because the kidney and liver are the main organs responsible for the elimination of toxins from the body, including the residues of drugs.

It is essential to determine that they are functioning normally during the administration of antimicrobials.

In most cases, to prevent accumulation and toxicity in patients with reduced renal or hepatic function or in cases of rapid hepatic metabolism.

This is due to the enzymatic induction due to the concomitant use of drugs such as rifampin or phenytoin, the concern is the dose to be administered.

Years

In patients at both ends of age groups, drugs operate differently, especially due to differences in body size and renal function.

Pediatric doses of medication are usually governed by weight.

In the case of geriatric patients, the serum creatinine level and creatinine clearance should be estimated, as well as age and weight.

Genetic variation

The genetic susceptibility to the adverse effects of antimicrobial agents is occasionally significant enough to justify testing for such variability before the administration of certain medications.

This is the case of the antiretroviral abacavir, which is part of the standard combination treatment for HIV infection, is associated with a life-threatening hypersensitivity reaction that can manifest itself with symptoms such as:

  • Fever.
  • Acne.
  • Abdominal pain.
  • Dyspnoea.

This reaction has been shown to be significantly greater in patients who have the human leukocyte antigen allele HLA-B * 5701.

Therefore, the current HIV treatment guidelines recommend the detection of this genetic susceptibility before prescribing this drug.

Pregnancy and lactation

Considerations for the use of antimicrobial agents during pregnancy are related to both the mother and the fetus.

In the mother, it is related to elevations in plasma volume and renal blood flow, especially in the third trimester, which may result in more rapid elimination and lower serum levels of antimicrobial agents.

Given this possibility, very high antimicrobial doses are generally not recommended during the third trimester of pregnancy.

In the developing fetus, many antimicrobial agents can be teratogenic or toxic to him.

In general, human studies on the safety of many antimicrobial agents during pregnancy and lactation are limited, and antimicrobial agents should be prescribed with great caution during these periods.

Allergy or intolerance

Information should normally be obtained in the evaluation when the medical history of the patient is made, to adverse reactions due to allergy or intolerance to antimicrobials, in order to define the treatment of the infection.

Oral vs. intravenous therapy

Hospitalized patients with serious infections are often treated with intravenous antimicrobial therapy, but patients with mild to moderate infections and normal gastrointestinal function are candidates for oral treatment.

On the other hand, patients who are initially treated with parenteral therapy can safely switch to oral antibiotics when they are clinically stable.

But in the case of more serious infections, such as infectious endocarditis and central nervous system infections such as Meningitis, a switch to oral therapy is unreliable and is usually not recommended.

Resistant bacteria

The WHO published a list of bacteria resistant to current treatments.

Classifying them into three groups called:

  • Priority pathogens.

They are those that cause infections in blood, lungs, brain and urinary tract and can be deadly: Acinetobacter baumannii, (with resistance to carbapenems), Pseudomonas aeruginosa, (with resistance to carbapenems), Enterobacteriaceae, (with resistance to carbapenems) .

  • Pathogens of high and medium priority.

In these bacteria the drug resistance is increasing and cause common diseases such as gonorrhea or food poisoning among others.

Of high priority we have:

  • Enterococcus faecium, (with vancomycin resistance).
  • Staphylococcus aureus, (with resistance to methicillin, have intermediate sensitivity and resistance to vancomycin).
  • Helicobacter pylori (with resistance to clarithromycin).
  • Campylobacter sp. (With resistance to fluoroquinolones).
  • Salmonellae (with resistance to fluoroquinolones).
  • Neisseria gonorrhoeae (with resistance to cephalosporin , resistant to fluoroquinolones).

Of medium priority:

  • Streptococcus pneumoniae (without sensitivity to penicillin).
  • Haemophilus influenzae (with resistance to ampicillin ).
  • Shigella spp. (With resistance to fluoroquinolones).