Discuss About The Diagnosis Antibiotic Stewardship Revisited?
The emerging resistance of the bacteria towards the antimicrobial therapy has leaded the awareness to reduce the overuse of the antibiotics in the treatment of the infectious disease. In spite of the use of the diagnostic marker in different fields of medicine, timely and accurate diagnosis of the bacteria induced disease remains a major challenge. There is a huge dearth in reliable microbiological and clinical parameters, which can be used to diagnose bacterial infection via ruling out other associated infection (1, 2). Inflammation markers such as C-reactive protein (CRP) or White Blood Cells (WBC) lack the desired specificity required to detect the bacterial infection (3). In the midst of this diagnostic dilemma, procalcitonin (PCT) is regarded as the potential biomarker for the bacterial infection. PCT is produced via ubiquitous reaction in response to the mediators or endotoxins generated because of bacterial infection. Interleukins (IL), tumour necrosis factor (TNF) are chemical mediators released because of the bacterial reactions and these mediators up regulate the concentration of PCT in blood. However, PCT is not suitable biomarker for viral infection because the pro-inflammatory cytokine, interferon gamma produced in response of viral propagation has been found to attenuate the synthesis of PCT. Nevertheless, this variance of up regulation and don regulation of PCT is used to discriminate between viral and bacterial infection (4-7). The concentration of PCT in blood increases with in 6 to 12 hours post bacterial stimulation and the concentration of circulating PCT decreases into half of the existing amount when the host immune system or antibiotics controls the infection. The amount of PCT in blood is co-related with the severity of infection and bacterial load (6-10).
PCT exhibit high diagnostic performance for the differentiating blood stream infection and bacteraemia. It is also used to discriminate contamination of blood from true infection in the blood stream, which is common in patients having growth of coagulase-negative staphylococci (11). 0.1 micro gram per litre of PCT has extremely high sensitivity to selectively exclude true infection in the blood (11). A cut of 0.25 micro grams per litre of PCT is used to predict the level of bacterial load in patient with urinary tract infection (UTI). In case of infectious endocarditic, the circulating levels of PCT get increased in comparison to the non-infected patients (12). PCT is used as a prognostic marker for sever bacterial diseases having adverse outcome. However, localized infections do not certainly induce the concentration of PCT (13).
In case of respiratory tract infections among the moderate risk patients, the charging and cessation of the antibiotic therapy is dependent on 4 different cut-off ranges. Initial administration of antibiotics is not recommended for the low risk patient with systemic infection of acute bronchitis or exacerbation of chronic obstructive pulmonary disease. On the other hand, repeated measurement and clinical re-evaluation of PCT are recommended after 6 to 24 hours if there is no spontaneous improvement of the clinical condition. Moreover, even after the initiation of the antibiotic therapy in response to the increased PCT, repeated PCT measurements are recommended. Such test must be conducted in every one to two days and must rely on the severity of the disease. The antibiotic discontinuation is done in response to a marked drop by 80% to 90% than the initial high levels. For high-risk patients in the ICU, discontinuation of antibiotic therapy if recommended if the PCT level gets decreased and patient experience clinical recovery (14).
The main objective of the study conducted by Sager, Kutz, Mueller and Schuetz published in the year of 2017 is he give a clear update to the clinical physicians regarding the present norms behind the PCT level and bacterial disease monitoring. The article here follows a meta analysis with a narrative review approach on the observational evidence interventional research articles published in-between 2012 and 2016. According to this paper, Procalcitonin-guided diagnosis and antibiotic stewardship revisited, the PCT cut-off in case of pulmonary infection must be less than 0.1-025 micro gram per litre in order to reduce the initiation of the antibiotic administration for the patient in emergency department of the hospitals and will have negligible adverse outcomes. The role of PCT is case of respiratory tract infection is extremely significant. PCT shows a firm impact on the detection and evaluation of the respiratory tract infection. The course of PCT acts as an important tool in dynamic monitoring. After the initiation of antibiotic, it is recommended to test the level of PCT after an interval of 3, 5 and 7 days. If the PCT levels are found decreasing, then the antibiotic cut-off must also be decreased following the same exponential range. However, if the PCT levels are found high, then the administration of the antibiotics can only be stopped if the PCT level gets decreased by 80 to 90 percent than the initial value. If the PCT levels are consistently high, even after the administration of the antibiotic then the treatment must be regarded as a failure. The likely hood of the bacterial infection increases in the respiratory tract when the PCT concentration in the blood is above 0.25 nago gram per milli litre. In case if cardiac complications, the range of PCT must be less than 0.25-0.5 micro gram per litre in order to reduce the initiation of the antibiotic administration for the patient in the primary care. It also helps in the detection of the bacterial super-infection in case if acute heart failure. For abdominal infection, the PCT guided antibiotic therapy leads to less antibiotic side-effects with no difference in the rate of mortality. For infection in the blood stream, sepsis, high PCT level has a direct sync with bacterial positive blood culture. In case of postoperative condition, low PCT level indicates the absence of the peri-operative infection and facilitates early discharge.
The paper gives a comprehensive summary of the evidence behind the use of PCT as a biomarker for the diagnosis of the microbial disease and antibiotic stewardship in organ-related infections. Among the infectious disease, Meningitis, Pneumonia, Upper respiratory tract infection, severe sepsis or septic shock provide strong evidence in the favour of the use of PCT as the principal biomarker. On the other hand, PCT provides good evidence of the antibiotic regulation for acute bronchitis, exacerbation of COPD (chronic obstructive pulmonary disorder), infection in the pulmonary fibrosis, asthma, congestive heart failure, abdominal infection, pancreatic infection, urinary tract infection and blood stream infection. Moderate evidence in favour of PCT exists in the diseases like post operative abdominal infection, endocarditis, appendicitis and arthritis. Neutropenia, in which the body has low level of neutrophill in blood due to certain infection, shows no evidence in favour of PCT.
PCT-guided therapy helps to decrease the rate of antibiotic exposure via decreasing the initiation or the tenure of the antibiotic treatment. PCT also improves the overall disease management of the patients with lower respiratory tract infections, sepsis, unrinary tract infection, postoperative infections, meningitis and other bacterial super infection like pneumonia. Recording the levels of PCT post hospitalization substantially reduces the use of antibiotic in low-risk situations. For infections, PCT kinetics helped in cutting short the duration of the antibiotic treatment. These strategies are safe and do not increase the chances of mortality, recurrent infections, or failure of the treatment.
According to me, this comprehensive review paper tried to clearly address the importance of monitoring the PCT level in blood during the management of the infectious disease. The paper also took a significant attempt to guide the clinicians to with the role of PCT in disease treatment and antibiotic administration. The authors here looked for the right and appropriate papers to perform this systemic review and have stringently cited recent studies conducted during the tenure of 2012 to 2016 focusing the role of PCT is disease treatment. All the important and relevant studies that have been conducted in this particular field are included in this research paper and clearly discussed in a collated manner. All the important outcomes, which are associated with the level of PCT in the blood are considered in detail and this include, the characterization of the infectious disease on the basis of their evidence in favour of PCT. The results obtained will be extremely useful for the healthcare professionals show nurture a common aim of providing the patients a relief from the symptoms, which are arising out of the bacterial infection. Moreover, the results are precise and are represented in a tabular format, further making it easier for the reviewer to comprehend the data.
However, I spotted certain loop holes in the study. The weakness of the study lies in the fact that it did not conduct a systematic review, rather selected articles in random from. Pubmed and hence the obtained conclusion is a bit enthusiastic or directed towards a single direction. Moreover, the selected papers did not blind investigators or patients and hence leading to possible chance of biasness. The meta analysis is performed over the research papers that are published during the tenure of 2012 and mid-2016. Papers before or after this particular time frame may have certain different approach on the PCT and its relation with biomarker of bacterial infection and hence, the possible conflicting data may have got missed. Moreover, the paper also failed to site a comparative analysis of the CRP and PCT and their role as a biomarker for infection and antibiotic stewardship. Moreover, the level of PCT in blood increases even in the absence of bacterial infection and such cases are common in patients with severe trauma or under post-operative condition (16). The paper only focused on the PCT as a biomarker for infection but failed to highlight the exceptional scenarios. In order to perform a comparative the study, the paper might have taken the approach as used by the paper Infection biomarkers in primary care patients with acute respiratory tract infections–comparison of Procalcitonin and C-reactive protein, such comparative approach will help the clinicians to understand the relation between CRP and PCT and how their blood levels helps in ascertaining the chronicity of the infection.
This narrative review put forward several interesting clinical settings for PCT-guided therapy. The therapy aims to decrease the level of antibiotic exposure via regulating the initiation or the duration of the overall treatment. PCT has been found to improve the overall management plan of the patients who are suffering from respiratory tract infections, septicaemia, UTIs, postoperative infections, meningitis and pneumonia. The reference of the PCT concentration in blood has helped to reduce the chances of initiation of strong antibiotic treatment in low-risk disease situations. In case of severe infections like pneumonia, antibiotic stewardship by regulating PCT kinetics helped in shortening the tenure of the antibiotic treatment and early cessation of therapy. These strategies are safe do not include the chance of mortality, recurrent infections and overall treatment failure.
There lays a strong relation with the antibiotic stewardship in the field of respiratory infection and sepsis of the blood. However, the concentration of PCT in the blood and it relation with other types of infectious disease has not been studied in details for several other types of infections. Thus, the scope of the future research lies on the relation of the PCT levels in the antibiotic treatment of the non-respiratory infections. The scope will also fall under the domain of investigating whether the concentration of PCT improves the antibiotic decision making process in these patients (non-respiratory infections). PCT must also be tallied with other biomarkers for infection such as CRP, on the scale of diagnostic accuracy and cost-effectiveness. The emergence of multidrug resistance bacteria has led to generation of the urgency of designing effective plan to reduce prolong and unnecessary intake antibiotics. The condition will again be of prime importance in case of self-limiting nonbacterial diseases.
The healthcare practitioner nurtures a common goal of achieving instant disease recovery via quick symptom relief in case of bacterial infection. In order to achieve the same, they administered high-dose antibiotic and the result is the generation of the multi-drug resistance bacteria ad recurrent infection. The importance of PCT lies in the fact that it promotes rational use of antibiotics in effective disease treatment.
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