Differentiating Cns Bacteremia From Contamination Biology Essay


One of the most isolated contaminants from blood cultures is coagulase negative staphylococcus (CoNS), though they frequently cause bloodstream infections (BSI). This distinction plays an important role on therapeutic implications in terms of using antibiotics that are not necessary and the emergence of resistance. In case of immunocompromised cancer patients, the failure of recognizing and treating true bacteremia will increase the rate of morbidity and mortality. Quantitative blood count (QBC) can aid in the interpretation of the significance of CoNS positive blood cultures but the method is not available in most laboratories. Another surrogate test that helps in the interpretation of positive blood cultures (BC) is time to positivity (TP). The authors concluded that patients with QBCs positive for a low colony count with a prolonged TP that implies CoNS contamination, therefore no need for therapeutic approach. Whereas patients with QBCs positive for a high colony count with shorter TP that implies that it might reflect true CoNS bacteremia, therefore adequate approach should be used.

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* 272 patients positive CoNS

* 72 were included in the 2 positive BC group

* 56 low colony count group

* 55 moderate colony count group

* 89 high colony count group

In order to decrease the high rate of overlap between moderate (10-100 CFU/ ml) and low (< 10 CFU/ml) colony count groups, patients with 10 to 30 CFU/ml were not included in the analysis.

The authors found statistically significant correlation between TP and CFU.

* In low colony count the median TP was 20.9 hours

* In moderate colony count the median TP was 1707 hours

* In high colony count the median TP was 11.6 hours

Therefore of ≤ 16hours suggested a high colony count and high grade bacteremia since 95% of patients in high colony count group had a TP of < 20 hours.


Patients with 2 positive BC group or with high colony count with TP ≤ 16 hours, requires antibiotic therapy or catheter removal or exchange.

Differentiating true catheter-related CoNS BSI from skin, intraluminal catheter and hub contamination is very important, in order to avoid unnecessary catheters, removal or exchange and it is also necessary in order to avoid and reduce selective pressure caused by inappropriate or unnecessary antibiotic treatment.

Unlike QBCs that is not widely performed in all hospitals, TP test is simple and valuable in many hospitals and cost free, but has some limitations and variations such as volume of the blood drawn and the incubation conditions.

The authors identified three limitations to their study:

1. This analysis was based on a retrospective evaluation of laboratory records.

2. Patient population included only hematologic or nonhematologic cancers, which may not be applicable to non cancer patients.

3. Different CoNS species would affect the reliability of TP since they may exhibit different growth kinetics.

Article 2: Determinig the Clinical Significance of Coagulase-Negative Staphylococci Isolated From Blood Cultures

The most organisms that are frequently isolated from BC are CoNS and play an important role in nosocomial bloodstream infections and at the same time, they are considered as the most common contaminants of BC. Contamination leads to additional laboratory tests, unnecessary antibiotic use, longer hospitalization, and an increase rate to morbidity and mortality due to failure of recognizing and treating true bacteremia. There is no specific gold standard that exists to differentiate between pathogenic CoNS and contaminants. Determining clinical and laboratory factors in association with episodes of blood culture contamination, and then using the factors to develop a definition for contamination, was the purpose of the study.


* Total of 405 BC were reviewed

* 89 were considered significant

* 316 were contaminants

Signs of species syndrome including fever, hypotension and tachypnea were more likely to appear in patients with CoNS bacteremia.

Vancomycin therapy was used for patients with CoNS bacteremia and also more than half of the patients with contaminated CoNS received Vancomycin therapy.

No patient with contaminated CoNS had more than 2 positive blood cultures whereas 53% of patients with true bacteremia had at least 2 positive blood cultures.

Optimal algorithm for determining the significance of blood culture positive for CoNS is recognized as follows:

* Blood culture positive for CoNS  ≥1 additional blood culture and in 5 days period significant

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* Blood culture positive for CoNS no additional blood culture and in 5days periodWBC < 2000 or > 12000 and ≥10% bands if no => contaminant if yes T< 36 or ≥38ËšC or SBP <90 if yes => significant and if no => contaminant.

53 of 405 episodes of positive blood culture in this study had1 blood culture performed in which 89% of these 53 isolates were considered contaminants, whereas most of the two positive blood cultures for CoNS were considered significant and absolute confidence in significance was achieved in 3 cultures positive for CoNS.

In this institution, CoNS was the most important cause of contaminated blood culture and the second most important cause of bacteremia.

The algorithm that is used for determining CoNS was at least 2 positive blood cultures within 5 days or 1 positive blood culture plus clinical evidence of infections. Proper determination leads to control over antibiotic use by reducing the inappropriate use of Vancomycin.

Article 4: Management of the Catheter in Documented Catheter-Related Coagulase-Negative Staphylococcal Bacteremia: Remove or Retain?

Nowadays, CoNS are considered an important pathogen that causes nosocomial blood stream infection (BSI) unlike the past where it was considered an unimportant organism. CoNS embed themselves by forming a multilayered biofilm matrix which enables them to adhere to the surface of the catheter. Eradication of the catheter is difficult once the biofilm layer is formed because microbial cells are protected from the antimicrobial activity by antibiotics including vancomycin.

In this study, CoNS were defined as true bacteremia on the basis of 3 criteria in addition to clinical signs and symptoms:

* At least 2 blood cultures should be available for all patients

* At least 1 blood culture should yield QBC ≥15 CFU/ml

* Blood sample that were positive, should have been collected within a 72 hour period.

Results: From the 910 positive blood cultures for CoNS, only 188 met the clinical and the microbiological criteria to be eligible for the study.

CoNS isolates were available for 81 patients in which Staphylococcus epidermidis dominated (93%), Staphylococcus hominis (5%), Staphylococcus capitis (1%), and Staphylococcus caprae (1%).

Bacteremia was resolved in 175 from 188 patients. Analysis showed that infection was 7 times more likely to fail to resolve in patients with an ICU stay prior to infection and 3.8 times more likely to fail to resolve in patients that have other parallel sites of infection. Analysis also showed that patients are less likely to have a recurrence if the catheter was removed or exchanged.

Central venous catheter is a significant risk factor of recurrence of bacteremia but it has no impact on the resolution of CoNS bacteremia.

Article 5: Clinical significance of potential contaminants in blood cultures among patients in a medical center

Blood culture is important for diagnosing species, but unfortunately, contamination is common which creates problems for interventions, rendering much efforts and expenses not required for both laboratory and zone personnel. According to the National Nosocomial Infectious Surveillance System and the surveillance data of pathogens of nosocomial BSI in their hospital, CoNS are leading cause in BSI and at the same time most frequent contaminant of blood cultures. The aims of this study were assessing the rates of potential contaminants found in the blood cultures (PCBC), the benefits behind repeating blood cultures in patients with PCBC and analyzing the clinical outcome of patients with true bacteremia and contaminant caused by PCBC.


* Total of 214 potential contaminants were found in blood culture. 85% were CoNS, 7% unidentified gram positive bacilli.

* 87% of the CoNS isolates were resistant to oxacillin which highlighted a potential in overuse of glycopeptides for pseudobacteremia patients.

* Overall contamination rate was almost 84% of all uses. 4% were treated with antibiotic (20% glycopeptides) that had no survival benefit.


It is very important to differentiate true from pseudobacteremia so that we reduce the unnecessary use of glycopeptides consumption so that we can holdup the emergence of resistance to glycopeptides.

The limitation of this study is that the discovery of the same antibiogram and bacterial species doesn't eliminate the possibility of being a contaminant in blood cultures for either isolates unless the genetic correlation is shown by molecular genotyping.

Article 6: Prevalence and significance of coagulase-negative staphylococci

isolated from blood cultures in a tertiary hospital

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Detecting BSI is done through blood culture and contamination mainly occurs through the process of collecting blood culture. CoNS are major blood culture infection (BCI) and at the same time they are frequently found in blood as contaminants. Contamination leads to unnecessary use of antibiotic and an increase costs in terms of laboratory work and patients care. The purpose of this study was determining the prevalencce and location of CoNS contaminated blood culture, risk factors of patients with BSI and the prescribing antibiotic used at St. Vincent's Hospital (SVH).


* 109 CoNS were isolated from a total of 4234 patients with blood culture collected.

* 94% of all CoNS were contaminants.

* 51% of all cases received therapy

* 52% from the 51% were treated with vancomycin

* Emergency departement(ED) , in comparison with the rest of the hospitals, had the highest blood culture contamination rate.

* Ward patients had the highest rate of being treated with vancomycin for a contaminant blood culture, in comparison with the rest of the hospitals.


At SVH, rates of contamination fell at 2.6% and could have fallen more if the blood cultures were not collected in ED which reflects poor collection procedure. An improvement for this could be done by assigning dedicated phlebotomists for blood cultures collection and educating the medical staff in order to reduce contamination rates.

The limitation of this study was the sample size.

Article 7: Routine antimicrobial susceptibility testing of coagulase-negative staphylococci isolated from blood cultures: is it necessary?

The leading cause of Nosocomial BSI are CoNS and at the same time they are common contaminants of blood cultures. The purpose of this research note was to see the clinical significance after stopping the routine AST of CoNS from blood culture.


* Antibiotic use did not change when AST was not done routinely, but the laboratory costs savings were 75% .

* Resistance of CoNS to oxacillin remained > 70%, therefore the authors suggest that it is not essential to do routine AST of CoNS isolated from blood culture.

Article 8: Clinical characterization of breakthrough bacteraemia:

a survey of 392 episodes .

Breakthrough bacteremia is different from recurrent bacteremia, since it is when the patient develops continuous or new onset bacteremia while receiving appropriate antibiotic against the microorganism whereas recurrent bacteremia is when bacteremia appears again after the patient had stopped taking antibiotic.


* From 6324 BSI, 392 met the breakthrough criteria and it was mostly common in the hematological hospitilization unit and 80% were nosocomial.

* Common source of infection was the endovascular (70%) and central intravenous devices (>50%)

* The most significant microorganisms involved were CoNS, Staphylococcus aureus and Pseudomonas aeruginosa.

Article 9: Long term trends in the occurrence of nosocomial blood stream infection

The objective of this study was to determine the drift in the occurrence of BSI at the University of Alberta Hospital. BSI is responsible for < 10% of the total nosocomial infections but its consequence leads to higher mortality prolonged length of hospitalization and higher cost of care than other infections.


* 2389 cases of nosocomial BSI in 10 years

* 57% of the total cases were due to primary infection resulting from intravascular devices followed by urinary tract, respiratory tract, and surgical site sources (10% each).

* Rate increased between 1986 and 1996 of nosocomial BSI from 6/1000 to 11/1000 admissions.

The common microbial organisms of BSI were: CoNS (27%), Staphylococcus aureus (19%), and enterococci (9%). Aerobic gram negative bacilli were detected in 28% of cases and candida in 6% of cases.


Research should be done urgently for the implementation of techniques in order to prevent central venous catheter infections, which is the most common cause of primary infections.

Article 10: Study of Coagulase Negative Staphylococci Isolated from Blood and CSF Cultures.

In the past, CoNS were thought out to be as laboratory contaminants and normal flora of skin, but they have emerged as opportunistic pathogens. This study highlighted on the prevelance rate of different species of CoNS that were isolated for blood culture and CSF cultures.


* 180 isolates of CoNS were studies.

* 70% were Staphylococcus epidermidis, 30% were Staphylococcus saprophyticus that were isolated from UTI.

* 75% of S. epidermidis were positive to slime test wehreas 15% of S.saprophyticus were positive to it. (Slime contain polysaccharide that help the bacteremia to interfere against antimicrobial activity).


Intensive study should be done due to the wide spread occurance of oxacillin resistant CoNS and the slow emergence of vancomycin resistant CoNS. The medical progress is increasing by time which is enhancing the risk of CoNS infection ( advanced cancer treatment, organ transplantation, implanted transplantation, etc.).

Article 11: History and evolution of antibiotic resistance in coagulase-negative staphylococci: Susceptibility profi les of new anti-staphylococcal agents

In this, paper the author highlighted the general problem of antibiotic resistance in CNS and discussed the susceptibility and resistance for specific species.

Historically, CoNS were more resistant to antimicrobials, including β-lactam antibiotics, than S.aureus. Resistance rate to oxacillin reached 90% in some hospitals, over the past 40 years, cross resistance to non-β-lactam agents started to appear in the CNS. Due to this increase resistance, newer antimicrobial agents were needed with good antistaphylococcal activity against CoNS. These new agents with excellent antistaphylococcal activity included: daptomycin, oritavancin, telavancin, tigecycline, dalbavancin, new quinolnes, and ceftibiprole. Biofilm formation in CoNS infection, lead to an increase in the MIC for most older antimicrobials. Several new antimicrobials play a role in penetrating the biofilm layer in order to inhibit or kill the adherent staphylococci.

In the modern age, CoNS will most probably stay a major cause of infection, resistance is increasing with time, therefore newer and developed antimicrobials are required for better therapy.

Article 12: Tolerance to the Glycopeptides Vancomycin and Teicoplanin in

Coagulase-Negative Staphylococci

Bactericidal treatment is required for CoNS infections. Glycopeptides antibiotics are being used since the resistance of CoNS to β-lactams is increasing.

This study is used to examine vancomycin and teicoplanin tolerance among clinical significant CoNS. The authors used the killing curve method, that is considered by the clinical and laboratory standard Institute (CLSI) to be the most reliable method. Antibiotic tolerance is a type of resistance in which the bacteremia is capable of surviving without growing, in presence of a lethal dose of bactericidal antibiotic.


* Initial set of 79 clinical significant CoNS isolates were studied, then another 11 set of isolated Staphylococcus lugdunensis were tested.

* From the 79 isolates, 66 were S. epidermidis, 4 S. hominis, 3 S. capitis, 2 S. lugdunensis, 2 S. warneri, 1 S. haemolyticus, and 1 S. pasteuri.

* Only S. lugdunensis species showed tolerance to glycopeptides.

* From the 13 isolates of S. lugdunensis, 6 strains exhibited tolerance to vancomycin or teicoplanin.

* Glycopeptides showed weaker and slower bactericidal activity, in the other 7 strains, in comparison to the other CoNS.


This study shows that glycopeptides are ineffective against S. lugdunensis species which is a major concern since it is recognized as one of the most pathogenic CoNS.

Article 13: Species Distribution and Antibiotic Sensitivity Pattern of Coagulase Negative Staphylococci Isolated From Various Clinical Specimens

CoNS were previously classified as contaminants but nowadays they are important pathogens. Therefore the authors highlighted the distribution and the antibiotic sensitivity patterns among CoNS species isolated from different specimens received in the bacteriology laboratory of Medical College, Amritsar.


* 192 strains of CoNS were isolated

* 82.3% were S.epidermidis isolated from all different clinical specimens.

* 15.6% were S.saprophyticus mainly from urine specimens.

* The remaining CoNS were S.cohnii and S.haemolyticus

* 48.7% of S.epidermidis were positive to slime test

* 26.7% of S.saprophyticus were positive to slime test.

AST results:

* >90% resistance to penicillin

* >50% resistance to cephalexin and ciprofloxacin

* >20% resistance to methicillin.

* All isolates were susceptible to vancomycin


The difference in AST of CoNS observed by various authors is mainly due to different protocols and strategies being applied by different hospitals concerning antibiotic use. So it is established to determine CoNS species and their antibiotic sensitivity for clinical isolates of CoNS

Article 14: Characterization of coagulase-negative staphylococcal isolates

from blood with reduced susceptibility to glycopeptides and therapeutic options

The aim of this study was to see if there is a clinical significant concern behind glycopeptide-resistant CoNS and the second aim is to distinguish if the bacterial infection were clonally related.


* 1609/17,418 blood culture were positive for CoNs

* 92/1609 associated with infection.

* 87/1609 (69 S.epidermidis, 18 S. haemolyticus) had reduced susceptibility to glycopeptide.

* 13/87 associated with infection

* All isolates are still susceptible to linezolid, daptomycin, and tigecyclin, but there was a high resistant against oxacillin (77%).

* One clonal relationship was identified between 2 isolates, admitted and confined in different periods, though fingerprinting of CoNS.


CoNS exist as normal flora in humans and used to be considered as a nonpathogenic organism, but due to an increase intravascular use and an increase cases of immunocompromise patients, CoNS became a major cause behind BSI.

Glycopeptides are the drugs of choice since CoNS are often resistant to multiple antibiotics, but because of the widespread of glycopeptides, CoNS are becoming less susceptible to them.

Clinical concern is emerging due to multi-resistant CoNS with reduced susceptibility to glycopeptides. So it is necessary to warn out clinicians through surveillance by antibyotyping and focusing on multi-resistant profile.

Article 15: Species Distribution and Antibiotic Resistance in Coagulase-negative Staphylococci Colonizing the Gastrointestinal Tract of Children in Ile-Ife, Nigeria

It is highly desirable to have an accurate species identification of CoNS due to its increase in the clinical significance. The purpose of this study is to evaluate the AST of CoNS isolated from fecal sample in an order to see their contribution to antimicrobial resistant in the community.


* 149 isolates of CoNS

* 30% S. epidermidis

* 17.5% S. haemolyticus

* 16% S. capitis.

* Resistance was more than 50% against β-lactams and there was reduced susceptibility against vancomycin

* Significant resistance was observed against cotrimoxazole chloromphenicol, tetracycline, erythromycin, fusidic acid and norfloxacin.


Many laboratories do not identify CoNS isolates at the species level since they are considered as only opportunistic infections although it is very important to identify it due to high rates of resistance.

Various authors had different AST profiles due to different geographical locations and hospital strategies of using antibiotics.

This study shows an increase in resistance, so the author suggests an appropriate use for antibiotic to stop the spread of resistance.

Article 20: Clinical significance of coagulase-negative staphylococci isolated from neonates.

CoNS used to be considered a rarely pathogenic organism but currently they are essential opportunistic organisms that produce severe infections. There is a high risk that these organisms cause nosocomial bacteremia in low-weight new born due to their long stay at the hospital. There is a high risk of contamination of blood culture during blood sampling which affect the identification of true bacteremia. Most laboratories do not use biochemical characteristics to identify CoNS although some authors say that identification is important to distinguish between contamination and infection.


* 117 CoNS strains isolated. (51.3% significant, 48.7% contaminant)

* 60 isolates from blood, 41 from foreign bodies, 13 from secretions and 3 from urine.

* From 60 isolates (58% significant, 42% contaminant.)

* Most infants infected were submitted to invasive procedures(using catheter, mechanical ventilation, etc)

* S.epidermidis was the main isolated species (78%)


Although S. epidermidis was the most isolated species causing infection, but there were other species like S.haemolyticus, S. lugdunesis, S. simulans, S. warneri and S.xylosus also caused infection which make identification of species among CoNs, important main sources was vascular catheters due to the easiness of skin microorganisms to colonize them, especially by CoNS. In this study three newborn died due to colonization of CoNS on foreign bodies despite antibiotic treatment.