sepsis can be difficult to distinguish from non - infectious conditions in critically ill or comatose patients in the early stages ; and diagnosis , treatment and outcomes greatly differ between patients with and without sepsis .
positive bacteriological cultures , including blood cultures , may not be available before 24 to 48 hours ; interpretation of local colonization may be ambiguous ; and traditional markers of infection , such as body temperature and white blood cell ( wbc ) count , may not be specific . furthermore , there are concerns about possible blood culture  negative clinical sepsis , particularly in the setting of increased prophylactic and empirical antibiotic use .
conversely , differentiating true infection from contamination after growth of common skin commensals in blood cultures , poses a diagnostic problem . since early identification of infections and
sepsis is crucial for patient management , an effective marker specific for bacterial infection is very useful in the critical care settings .
there are several markers of sepsis , like c - reactive protein , serum procalcitonin ( pct ) , il-6 , il-8 , lactate , etc . , of
pct has been proposed as an indicator of the presence of infection and as a useful marker of the severity of sepsis .
the present study was an attempt to assess the usefulness of serum pct as a marker of sepsis in critically ill patients , using the semi - quantitative , rapid immunochromatographic kit , in apollo hospitals , bangalore .
this study was carried out from july 2007 to june 2008 in the department of microbiology , apollo hospitals , bangalore .
the study included patients from the intensive care unit ( icu ) with suspected sepsis .
sepsis was confirmed clinically and by positive blood culture ( bact / alert system ) .
( sepsis , severe sepsis , septic shock ) or no sepsis based on the accp ( american college of chest physicians ) recommendations .
serum pct was assayed semi - quantitatively by rapid immunochromatographic technique using a commercially available test kit ( pct - q , b.r.a.h.m.s .
the result was independently read by two microbiologists to minimize reading bias and interpreted as per the manufacturer 's recommendations : 
 i)pct > 10 ng / ml : severe bacterial sepsis or septic shockii)pct 2 to 10 ng / ml : severe systemic inflammatory response , most likely due to sepsis unless other causes are knowniii)pct 0.5 to 2 ng / ml : a systemic infection can not be excludediv)pct < 0.5 ng / ml : local bacterial infection possible ; sepsis unlikely 
  pct > 10 ng / ml : severe bacterial sepsis or septic shock pct 2 to 10 ng / ml : severe systemic inflammatory response , most likely due to sepsis unless other causes are known pct 0.5 to 2 ng / ml : a systemic infection can not be excluded pct < 0.5 ng / ml : local bacterial infection possible ; sepsis unlikely the clinical condition , signs and symptoms of sepsis , antibiotics used , blood culture and final outcome of patients were recorded for all patients .
sensitivity and specificity of the pct assay were analyzed using two different cut - off values for pct ( 0.5 ng / ml and 2 ng / ml ) ; sensitivity being pct positives / total no .
of sepsis cases  100 and specificity being pct positives / total no . of cases without sepsis
statistical analysis was carried out using chi - square test to evaluate the correlation between pct levels and sepsis .
sensitivity and specificity of the pct assay were analyzed using two different cut - off values for pct ( 0.5 ng / ml and 2 ng / ml ) ; sensitivity being pct positives / total no . of sepsis cases
statistical analysis was carried out using chi - square test to evaluate the correlation between pct levels and sepsis .
patient ages ranged from 18 to 84 years [ male - female ratio , 28:12 ] . among these patients ,
pct above 10 ng / ml was seen in 12 patients ; 2 - 10 ng / ml , in 7 patients ; 0.5 - 2 ng / ml , in 3 patients ; and < 0.5 ng / ml , in 18 patients [ table 1 ] .
serum procalcitonin values in the 40 patients with suspected sepsis among the 12 patients with pct > 10 ng / ml , 1 patient in shock did not have any signs of sepsis or infection and recovered with inotropic support only ( no antibiotics were required ; cardiogenic shock )
. of the 11 patients with clinically diagnosed sepsis , 8 yielded positive blood cultures subsequently ( 2 patients with septic shock had staphylococcus aureus bacteremia ) ; 1 patient had rickettsial disease with a typical clinical presentation ( fever , skin rashes , altered sensorium ) , which was confirmed by a positive weil felix reaction which showed elevated titres and a rise in titre within a week , and responded well to doxycycline and supportive therapy ; and 2 patients with negative blood cultures were on empiric antimicrobial therapy .
four patients in this group expired due to complications of sepsis ( mortality , 33.3% ) .
one of the patients with renal transplant and with features of sepsis had a serum pct > 10 ng / ml ( day 1 ) .
he responded to parenteral meropenem and teicoplanin , and his subsequent serum pct levels reduced to < 0.5 ng / ml on day 3 and day 5 .
all 7 patients with pct of 2 - 10 ng / ml had some form of sepsis ( sepsis , 4 patients ; severe sepsis , 2 ; and septic shock , 1 patient ) .
four of them yielded positive blood cultures ; 1 patient had parasitemia ; and 2 malignancy patients with febrile neutropenia who were on empiric antimicrobial therapy had negative blood cultures .
of the 3 patients with pct of 0.5 - 2 ng / ml , 1 patient had clinical evidence of sepsis secondary to culture - proven pseudomonas bronchopneumonia , though his blood culture did not yield any organism .
he responded well to a combination therapy of cefoperazone - sulbactam and amikacin and was stable at discharge .
the other 2 patients had no evidence of infection ( congestive cardiac failure and unstable angina ) , and 1 of them expired due to cardiac complications .
of the 18 patients with pct < 0.5 ng / ml , only 2 patients with bronchopneumonia had evidence of sepsis .
among 3 other patients with infections , 1 patient had lobar pneumonia but without sepsis ; 1 , pyrexia of unknown origin ( possibly a viral infection ) ; and 1 , probable viral encephalitis but no signs of sepsis .
two patients ( post - myomectomy hypertrophic obstructive cardiomyopathy and acute myocardial infarction ) with positive blood cultures ( s. epidermidis and s. haemolyticus ) were concluded to have cardiogenic shock and not septic shock , as they responded well to inotropic support . in 1 of them , antibiotics were given additionally , considering his postoperative status ( single - vessel stenting done 3 days prior to pct testing ) . in this cohort , in a patient with a differential diagnosis of food botulism , a low pct assisted in excluding an infective aetiology , and the patient was subsequently diagnosed as having acute oculobulbar syndrome . in 8 out of the 9 fatal cases ,
serum pct cut - offs of 0.5 ng / ml and 2 ng / ml were analyzed separately for their sensitivity and specificity as biomarkers for sepsis among the 21 patients with sepsis and 19 patients without sepsis .
there was a statistically significant correlation with the presence of sepsis determined using either pct 0.5 ng / ml or 2 ng / ml ( p<0.0001 in both cases ) . using 0.5 ng / ml or more as cut - off , 19 of the 21 patients with sepsis could be detected , but 3 out of the 19 patients without sepsis showed pct above 0.5 ng / ml ( sensitivity , 90% , i.e. , 19/19 + 2 ; and specificity , 84% , i.e. , 16/16 + 3 ) .
using pct cut - off of 2 ng / ml or more as a marker of sepsis , 18 of the 21 patients with sepsis could be detected by pct , and only 1 out of the 19 patients without sepsis showed pct above 2 ng / ml ( sensitivity , 85.7% , i.e. , 18/18 + 3 ; and specificity , 94.7% , i.e. , 18/18 + 1 ) [ table 2 ] .
relation of serum pct levels with sepsis , number of patients ( blood cultures ; mortality )
the aim of this study was to assess the usefulness of serum pct as a marker of sepsis in critically ill patients in our hospital .
early identification of infection and sepsis in critically ill patients is a challenge for clinicians .
serum pct has been found to be a very good indicator of sepsis syndrome . to the best of our knowledge
these include studies on its use in determining bacterial sepsis in children with febrile neutropenia , its use as a marker of renal parenchymal infection and its use as a marker of the severity of acute pancreatitis.[68 ] most studies using pct for interpretation of bacterial infection and sepsis have used the quantitative pct assay ( immunoluminometric method ) .
several studies have achieved high sensitivity and modest specificity with a cut - off of 1 to 1.2 ng / ml .
others have used 2 ng / ml as the diagnostic threshold for infection and sepsis .
various studies have found the pct values in sepsis ranging from 0.5 to 3.5 ng / ml ; in severe sepsis , 6.2 - 9.1 ng / ml ; and in septic shock , 12.8 to 38.5 ng / ml . on the other hand , semi - quantitative pct assay is a rapid immunochromatographic assay and is easy to perform .
the method shows good sensitivity and specificity in diagnosing bacterial sepsis at pct levels of 2 ng / ml.[1315 ] using pct levels above 2 ng / ml as the cut - off to indicate sepsis syndrome , the present study showed sensitivity of 86% and specificity of 95% . using a cut - off of above 0.5 ng / ml revealed higher sensitivity but with a reduction in the specificity to 84% .
hence serum pct of 2 ng / ml or more using the rapid immunochromatographic method is an effective marker of sepsis and may help in aggressive management of such patients along the lines of sepsis . despite improved methods , blood cultures are not always positive in clinically confirmed sepsis .
presumed bacterial cause of fever can not be detected in 60% to 80% of patients with suspected primary and secondary bloodstream infections . in this study , excluding the 2 cases of malaria and rickettsial fever , the sensitivity of blood culture was 63% ( 12 of 19 ) ; and in all these patients , serum pct was above 2 ng / ml . differentiating true infection from contamination or probable skin commensals in blood cultures poses a diagnostic problem .
the 2 blood cultures yielding coagulase - negative staphylococci were probable skin commensals , as both patients did not have any infective foci and both responded well with inotropes alone . in both these patients ,
the serum pct was less than 2 ng / ml . falsely high pct is known to occur in cardiogenic shock , major surgery , accidental trauma , pancreatitis and burn patients . of patients with cardiogenic shock , 1 patient had pct above 10 ng / ml , 2 had pct less than 0.5 ng / ml and 1 patient with coexisting sepsis had pct of 2 - 10 ng / ml .
pct levels are significantly higher in patients with septic shock than in those with cardiogenic shock , and hence a cut - off of above 10 ng / ml is recommended to discriminate between septic and cardiogenic shocks .
serum pct increases early after trauma and peaks within 48 to 72 hours post - trauma and declines thereafter in the absence of infection or sepsis . in the present study , out of 13 patients with major surgery or trauma , 4 patients had surgery or trauma with in 72 hours of suspected sepsis and pct testing ; 3 of them with pct levels below 0.5
ng / ml did not have sepsis , and 1 patient had septic shock ( pct > 10 ng / ml ) .
in contrast , initial falsely low pct levels , typically seen during the early course or localized state of infection , often show a gradual increase during follow - up measurements after 6 - 24 hours .
reduction in concentration of pct has been described in response to antibiotic administration and may be used to detect antibiotic responsiveness . in the present study ,
serial serum pct levels were not estimated for most patients . however , one of the patients ( post - renal transplant status ) from this cohort for whom 3 serum pct levels were performed showed a marked decrease in the pct levels in response to the antibiotics administered .
this is in concordance with the several clinical - management protocols , like the  pct - guided antimicrobial stewardship 
, that have been used to either withhold or continue antibiotics based on the pct levels .
a limitation of the present study is that serial measurements of pct were not done for most patients .
more indian studies evaluating pct on a larger number of patients with suspected sepsis are needed to conclusively corroborate the findings of this study , and such studies will be useful in an age of overuse of antibiotics and emerging antibiotic resistance .
another limitation of the study was that c - reactive protein ( crp ) levels were not estimated for most patients .
however , most studies have found superiority of pct in comparison to crp as a marker of infection and sepsis .
the pct assay was found to be a promising biomarker of sepsis in this small exploratory study and provided valuable and early information before the culture results were available .
the semi - quantitative , rapid assay revealed moderate sensitivity ( 86% ) and high specificity ( 95% ) at a cut - off above 2 ng / ml .
pct assay might assist in avoiding unwarranted antibiotic usage in critically ill patients who present with symptoms similar to those in infective conditions .
however , the assay result must be interpreted in association with the clinical findings and other laboratory parameters .
 sepsis can sometimes be difficult to substantiate , and its distinction from non - infectious conditions in critically ill patients is often a challenge . 
 serum procalcitonin ( pct ) assay is one of the biomarkers of sepsis . 
 the present study was aimed to assess the usefulness of pct assay in critically ill patients with suspected sepsis . 
 the study included 40 patients from the intensive care unit with suspected sepsis . 
 sepsis was confirmed clinically and/or by positive blood culture . 
 serum pct was assayed semi - quantitatively by rapid immunochromatographic technique ( within 2 hours of sample receipt ) . among 40 critically ill patients , 21 
 had clinically confirmed sepsis . 
 there were 12 patients with serum pct 10 ng / ml ( 8 , blood culture positive ; 1 , rickettsia ; 2 , post - antibiotic blood culture sterile ; and 1 , non - sepsis ) ; 7 patients with pct 2 - 10 ng / ml ( 4 , blood culture positive ; 1 , falciparum malaria ; 2 , post - antibiotic blood culture sterile ) ; 3 patients with pct of 0.5 to 2 ng / ml ( sepsis in 1 patient ) ; and 18 patients with pct < 0.5 ng / ml ( sepsis in 2 patients ) . patients with pct  2 ng / ml had statistically significant correlation with the presence of sepsis ( p<0.0001 ) . 
 the pct assay revealed moderate sensitivity ( 86% ) and high specificity ( 95% ) at a cut - off  2 ng / ml . 
 the pct assay was found to be a useful biomarker of sepsis in this study . the assay could be performed and reported rapidly and provided valuable information before availability of culture results . 
 this might assist in avoiding unwarranted antibiotic usage . 
INTRODUCTION
METHODS
Statistic analysis
RESULTS
DISCUSSION
CONCLUSION