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CAPÍTULO 2. CONCEPTUALIZACIÓN DE LAS VARIABLES DE INVESTIGACIÓN.

3.12. EL BURNOUT Y LA RELACIÓN CON LA PERSONALIDAD

A total of 388 patients with sepsis were recruited for the study. None of the patients were enrolled more than once - that is, there was 1 episode per patient. There were 233 males (60%) and 155 females (40%), giving a male to female ratio of 3:2. Most of the patients recruited were in the neonatal age group (46.6%). The median age was 75 days with minimum of 3 days and maximum of 16 years. The study population was divided into 5 groups based on age (figure 1).

The 388 patients enrolled were classified into two groups, group I (bacteremic) and group II (non-bacteremic) according to the presence or absence of pathogenic organisms isolated from their blood culture. Bacteremic and non-bacteremic episodes accounted for 132 (34%) and 256 (66%) of all cases respectively. An episode was considered bacteremic if two positive blood cultures yielded the same isolate.

Antibiotics had been administered to 67% (259) of patients before admission into the study.

Ninety-two (35.5%) of these patients had positive blood cultures constituting 69.7% of the bacteremic group. In both bacteremic and non-bacteremic groups, prior use of antibiotics was commonest among the 12-16 years age group followed by the neonatal age group (Table 1). There was no significant difference between the bacteremic and non-bacteremic groups with regard to previous antibiotic therapy (p > 0.05) (Chi-squared test).

42 Figure 1: Age and sex distribution of paediatric patients with sepsis in LUTH.

0 20 40 60 80 100 120

≤ 28 days 29 days - < 1 year

1 year - < 5 years

5 years - < 12 years

12 years - 16 years

male female

43 Table 1: Antibiotic usage prior to admission into the study among the different age groups of patients with sepsis in LUTH

Age Groups Antibiotic Usage Bacteremic Group (N=132)

Non-Bacteremic Group (N=256)

Yes (%) 51 (76.1%) 16 (61.5%) 16 (61.5%) 5 (62.5%) 4 (80%) 92

No (%) 16 (23.9%) 10 (38.5%) 10 (38.5%) 3 (37.5%) 1 (20%) 40

Yes (%) 86 (75.4%) 26 (49.1%) 34 (59.6%) 14 (60.9%) 7 (77.8%) 167

No (%) 28 (24.6%) 27 (50.9%) 23 (40.1%) 9 (39.1%) 2 (22.2%) 89

< 28 days

29 days - < 1 year 1 years - < 5 years 5 years - < 12 years 12 years – 16 years Total

44 Gram negative bacilli were responsible for 74 (56.1%) of the 132 bacteremic episodes followed by gram-positive cocci in 56 (42.4%) episodes and yeast in two (1.5%) episodes.

Gram negative bacilli were the most common isolates among the neonatal age group, less than 5 years age group and the 12 – 16 years age group (Figure 2). However, the most frequently isolated organism among the neonatal age group was Klebsiella pneumoniae, Staphylococcus aureus was the most common among the less than 1 year age group as well as the less than 5 years age group. Coagulase Negative Staphylococcus (CoNS) was the most predominant organism among the less than 12 years age group and 12-16 years age group.

Among the 388 patients, 226 (58.2%) patients had serum procalcitonin (PCT) level below the detection limit of the test (PCT < 0.5ng/ml). All the patients with PCT below 0.5ng/ml were in the non-bacteremic group. Forty-seven (12.1%) patients had PCT > 0.5ng/ml, 31 and 16 in the bacteremic and non bacteremic groups respectively. Seventy-five (19.3%) patients had PCT >2ng/ml, 65 and 10 in bacteremic and non-bacteremic groups respectively.

Forty (10.3%) patients had PCT > 10ng/ml, 36 and 4 in the bacteremic and non-bacteremic groups respectively (Figure 3). The different PCT levels were statistically significant between group I and group II i.e. the bacteremic and non-bacteremic groups (p< 0.001) (Chi-squared test).

In the bacteremic group, 3 patients with gram negative bacteremia had PCT > 0.5ng.ml and 26 patients in the gram positive bacteremia respectively. Forty-one patients with gram negative bacteremia had >2ng/ml and 24 patients with gram positive bacteremia respectively. Thirty patients with gram negative bacteremia had PCT >10ng/ml with 6 in the gram positive bacteremia respectively (figure 4). The mean serum PCT level was

45 5.182±4.0189ng/ml in the gram negative bacteremic category while it was 2.161±2.8318ng/ml. When comparing the gram negative and gram positive bacteremic categories, PCT levels were significantly higher in the gram negative bacteremia (p< 0.001) (Chi-squared test).

With a threshold for the cutoff value of PCT at > 0.5ng/ml in relation to positive blood culture results, the sensitivity was 97%, specificity was 90.4%, positive predictive value was 84.6% while the negative predictive value was 98.2% (Table 2).

Forty-five (11.6%) of the 388 patients died during the hospital stay, 19 and 26 of these were in the non-bacteremic and bacteremic group respectively. Forty percent (16) of patients with PCT > 10ng/ml died, followed by 13.3% (10) of those with PCT > 2ng/ml, 8.5% (4) and 6.6% (15) of those with PCT > 0.5ng/ml and < 0.5ng/ml respectively (Table 3). The neonatal age group had the highest mortality (40%) followed by the less than one year age group (Figure 5). There was higher mortality rate (68%) among the patients with gram negative bacteremia compared to those with gram positive bacteremia (32%) (Table 4).

One hundred and thirty two patients had positive blood culture while the remaining 256 patients had negative blood culture despite presenting with a clinical picture suggestive of sepsis. Though 24 out of the 256 patients had contaminants isolated in their blood cultures (contaminant, isolation of skin flora in one bottle). All culture positive samples had single organism in two blood culture bottles. Klebsiella pneumoniae was the most common pathogen encountered followed by Staphylococcus aureus and Coagulase Negative Staphylococci. Other gram negative isolated were Enterobacter species, Serratia species, Salmonella choleraesius and Escherichia coli. Other isolates were Enterococcus specie, Raoutella species, Burkholderia cepacia, Acinetobacter baumanii, Pseudomonas aeruginosa and Candida albicans.

46 Figure 2: The distribution of the isolates in bacteremic group among the different age groups in pediatric patients with sepsis in LUTH.

GNR-Gram negative rods, GPC-Gram positive cocci, CAN- Candida species

0 5 10 15 20 25 30 35 40 45

≤ 28 days 29 days - < 1 year

1 year - < 5 years

5 years - < 12 years

12 years - 16 years

Number ofpatients

Age groups

GNR GPC CAN

47 Figure 3: PCT levels in pediatric patients with bacteremic and non-bacteremic episodes in LUTH. PCT level of > 2ng/ml was highly suggestive of bacteremia.

0 50 100 150 200 250

<0.5 >0.5 <2 >2 <10 >10

Number of patients

PCT Levels

Negative Blood Culture Positive Blood Culture

48 Figure 4: Effect of organism type on PCT levels in paediatric patients with gram negative and gram positive bacteremia with candidaemia in LUTH. GNR-Gram negative rods, GPC- Gram positive cocci, CAN- Candida species

0 5 10 15 20 25 30 35 40 45

< 0.5 > 0.5 - < 2 > 2 - < 10 > 10

Number of patients

Procalcitonin levels (ng/ml)

GNR GPC CAN

49 Table 2: Sensitivity and specificity of PCT values in relation to the gold standard (blood culture)

Disease status (gold standard – blood culture)

Positive Negative Total

Test Positive 132 (TP) 24 (FP) 156

Negative 4 (FN) 228 (TN) 232

Total 136 252 388

50 Table 3: PCT levels among the different age groups of septic pediatric patients with mortality outcome in LUTH.

Age groups PCT levels (ng/ml)

< 0.5 (N=226) n (%)

>0.5 - < 2 (N=47)

n (%)

>2 - < 10 (N=75) n (%)

>10 (N=40) n (%)

≤ 28 days

29 days – < 1 year 1 year - < 5 years 5 years - < 12 years 12 years – 16 years Total

7 (3.1) 3 (1.3) 2 (0.9) 3 (1.3) 0 (0) 15 (6.6)

1 (2.1) 3 (6.4) 0 (0) 0 (0) 0 (0) 4 (8.5)

4 (5.3) 4 (5.3) 0 (0) 1 (1.3) 1 (1.3) 10 (13.2)

6 (15) 3 (7.5) 4 (10) 0 (0) 3 (7.5) 16 (40)

51 Figure 5: Mortality rates among the different age groups of pediatric patients with sepsis in LUTH. Number of patients, N = 45

0%

5%

10%

15%

20%

25%

30%

35%

40%

≤ 28 days 29 days - < 1 year

1 year - < 5 years

5 years - < 12 years

12 years - 16 years

Mortality rate

Age groups

52 Table 4: Mortality rates and PCT levels among the non-bacteremic and bacteremic groups of septic pediatric patients in LUTH

PCT levels (ng/ml) Non-bacteremic (N=256)

n (%)

Bacteremic GNR (N=74)

n (%)

GPC (N=56) n (%)

Pa

< 0.5

>0.5 - < 2

>2 - < 10

>10

15 (5.9) 1 (0.4) 2 (0.8) 1 (0.4)

0 (0) 0 (0) 6 (8.1) 11 (14.9)

0 (0) 2 (3.6) 2 (3.6) 4 (7.1)

0.001

a Chi- squared test

53 The susceptibility profiles of the isolates were grouped along Gram stain results. There were 3 Gram positive isolates – Enterococcus spp, Coagulase negative Staphylococci and Staphylococcus aureus. 64.2% of Gram positive isolates were susceptible to Co-Amoxiclav, 69.6% Ampicillin/Sulbactam, 75% to Piperacillin/Tazobactam, 62.5% to Levofloxacin, 53.6% to Gentamicin, 46.4% to Erythromycin, 62.5% to Clindamycin, 66.1% to Chloramphenicol, 75% to Rifampicin, 47.6% to Cefuroxime, and 96.4% to Vancomycin.

(Table 5)

Further resistance testing showed 54.5% of Staphylococcus aureus were Methicillin Resistant (MRSA) and 50% of the Coagulase negative Staphylococci were Methicillin Resistant. On the other hand, all Enterococcus species and Coagulase negative Staphylococci were susceptible to Vancomycin while 83.3% of MRSA were susceptible to Vancomycin (Table 6).

The susceptibility pattern of Gram negative organisms (fermenters) showed over 50% of the isolates were susceptible to Amikacin, Ertapenem, levofloxacin and meropenm while less than 25% of the isolates were susceptible to co-amoxiclav, Ceftazidime and Cefotaxime (Table 7).

The gram negative organisms (non-fermenters) showed high susceptibility pattern to ampicillin/sulbactam, piperacillin/tazobactam, levofloxacin, amikacin and Meropenem (Table 8).

The result of resistant phenotypes among the gram negative bacilli showed 67.6% of Gram negative (fermenters) were Extended Spectrum Beta-Lactamase (ESBL) producers while none was Modified Hodge Test (MHT) positive. Klebsiella pneumoniae (33.8%) was the commonest ESBL producers followed by Enterobacter cloacae (22.1%). None of the non-fermenter gram negative bacilli produced ESBL.

54 Table 5: Susceptibility Rates of Gram Positive Isolates.

Organisms N AMC

%

SAM

%

TZP

%

LEV

%

GEN

%

E

%

CLI

% C

%

RD

%

CXM

%

VA

% Enterococcus

spp

14 50 71.4 71.4 57.1 57.1 50 NT 93 71.4 NT 100

CoNS 20 50 70 70 60 45 55 65 60 70 40 100

S aureus 22 22.7 68.1 81.9 69.2 59.1 59.9 69.2 64.6 79.9 64.4 83.3 Total 56 64.2 69.6 75 62.5 53.6 46.4 66.6 66.1 75 47.6 96.4

AMC = Co-Amoxiclav, SAM = Ampicillin-Sulbactam, CXM = Cefuroxime, LEV = Levofloxacin, CLI = Clindamycin, GEN = Gentamicin, TZP = Pipercillin-Tazobactam, E = Erythromycin, C = Chloramphenicol, RD = Rifampicin, VA = Vancomycin.

CoNS – Coagulase Negative Staphylococci S aureus – Staphylococcus aureus

55 Table 6: Detection of resistant phenotypes in Gram positive cocci

Resistant phenotypes

Number tested Positive Negative Percentage

MRSA 22 12 10 54.5

MRCoNS 20 10 10 50

VRE VRCoNS

14 10

0 0

14 10

0 0

VRSA 12 2 10 16.7

MRSA = Methicillin Resistant Staphylococcus aureus, MRCONS = Methicillin Resistant Coagulase Negative Staphylococci, VRE = Vancomycin Resistant Enterococci. VRSA = Vancomycin Resistant Staphylococcus aureus.

Two (16.7%) of MRSA isolates were resistant to vancomycin.

56 Table 7: Susceptibility rates of Gram Negative Isolates (Fermenters)

Organisms N AMC

%

TZP

%

CAZ

%

CTX

%

FEP

%

LEV

%

AK

%

ATM

%

MEM

%

ETP

% Klebsiella

spp.

26 7.7 26.9 0 0 15.4 65.3 50 19.2 65.3 46.2 Enterobacter

spp.

22 13.6 27.2 13.6 9.1 18.2 54.5 54.5 22.7 72.7 68.2

Serratia spp 5 0 40 60 0 0 80 80 0 20 20

Salmonella cholerasus

5 100 100 100 100 100 100 NT 100 100 100 Rauotella

spp.

2 0 0 0 0 0 0 50 0 50 50

E. coli 7 71.4 85.7 42.9 42.9 57.1 71.4 85.7 42.9 85.7 57.1 Citrobacter

brakii

1 0 100 100 0 100 100 100 0 100 0

Total 68 22.1 41.2 23.5 14.7 26.5 66.2 50 26.5 69.1 54.4

AMC = Co-Amoxiclav, LEV= Levofloxacin, TZP = Pipercillin-Tazobactam, AK =

Amikacin, MER = Meropenem, CAZ = Ceftazidime, CTX = Cefotaxime, CEF = Cefepime, ATM = Aztreonam, ETP = Ertapenem, NT = not tested.

Over 50% of the gram negative enterobacteriaceae were susceptible to amikacin, levofloxacin, ertapenem and meropenem.

57 Table 8: Susceptibility Rates of Gram Negative Isolates (Non-Fermenters)

Organisms N SAM

%

TZP

%

LEV

%

CAZ

%

CTX

%

FEP

%

AK

%

ATM

%

MEM

% P. aeruginosa 1 NT 100 100 100 NT 0 100 0 100

A. baumanii 1 100 100 0 100 0 0 100 NT 100

B. cepacia 4 NT NT 100 25 NT NT NT NT 100

Total 6 100 100 100 50 0 0 100 0 100

AMC = Co-Amoxiclav, SAM = Ampicillin-Sulbactam, LEV = Levofloxacin, CAZ = Ceftazidime, CTX = Cefotaxime, FEP = Cefepime, AK = Amikacin, ATM =Aztreonam, MEM = Meropenem, TZP = Piperacillin-Tazobactam.

The gram negative isolates (non-fermenters) displayed high susceptibility to the carbapenems, quinolone (levofloxacin), amikacin and the beta lactam/beta lactam inhibitor combinations but were resistant to the extended spectrum cephalosporins.

58 CHAPTER FIVE

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