Comparison of cerebrospinal fluid lactate with physical, cytological, and other biochemical characteristics as prognostic factors in acute bacterial meningitis

De Almeida, Sérgio Monteiro; Barros, Nagyla C.; Petterle, Ricardo; Nogueira, Keite

doi:10.1590/0004-282X20190185

Sérgio Monteiro De Almeida Correspondence: Sérgio Monteiro de Almeida; Hospital de Clínicas, UFPR, Seção de Virologia, Setor Análises Clínicas; Rua Padre Camargo, 280; 80060-240 Curitiba PR, Brasil; E-mail: sergio.ma@ufpr.br

Universidade Federal do Paraná, Hospital de Clínicas, Curitiba PR, Brasil

https://orcid.org/0000-0001-5690-105X

Nagyla C. Barros

Universidade Federal do Paraná, Hospital de Clínicas, Curitiba PR, Brasil

Ricardo Petterle

Universidade Federal do Paraná, Hospital de Clínicas, Curitiba PR, Brasil

https://orcid.org/0000-0001-7735-1077

Keite Nogueira

Universidade Federal do Paraná, Hospital de Clínicas, Curitiba PR, Brasil

https://orcid.org/0000-0001-5655-9645

Correspondence: Sérgio Monteiro de Almeida; Hospital de Clínicas, UFPR, Seção de Virologia, Setor Análises Clínicas; Rua Padre Camargo, 280; 80060-240 Curitiba PR, Brasil; E-mail: sergio.ma@ufpr.br

Conflict of interest: There is no conflict of interest to declare.

Figures (3)
Tables (3)

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Figure 1
Comparison of cerebrospinal fluid (CSF) variables between the groups with positive (survival) and negative (death) outcomes. A. CSF lactate (mmol/L) in the last sample. B. Variation of CSF lactate concentration between the first and last sample. C. CSF color index (%) in the last sample. D. Mean CSF color index (%) in all longitudinal samples.

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Figure 2
Kaplan-Meier survival curves. A. Survival curve for the mean cerebrospinal fluid (CSF) lactate concentration (mmol/L) in longitudinal CSF samples. B. Survival curve for the CSF lactate concentration (mmol/L) in the last CSF sample. C. Survival curve for the CSF lactate concentration (mmol/L) in the first CSF sample. A, B, C Continuous line CSF lactate < 3.5 mmol/L; dashed line CSF lactate > 3.5 mmol/L. D. Survival curve for variation of the CSF lactate concentration between the first and the last sample (mmol/L); continuous line, CSF lactate < 1.4 mmol/L, dashed line CSF lactate > 1.4 mmol/L. The cut-off point was calculated by the median of the variation of the CSF lactate concentration in the longitudinal samples in the total group. E. Survival curve for CSF color index (%) in the last CSF sample; continuous line, CSF colorless (color index 0%); dashed line CSF xanthochromia (color index > 0%). F Survival curve for age (years) of the patients, continuous line age < 29.31 years, dashed line age > 29.31 years.

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Figure 3
Dynamics of the cerebrospinal fluid (CSF) lactate concentration (mmol/L) in patients with multibacterial meningitis, according to outcome. The continuous line indicates the positive-outcome (survival) group; the dashed line indicates the negative-outcome (death) group. The full circle indicates the CSF sample with positive cultures for bacteria different from that isolate from the first CSF sample. Bacteria identified in multibacterial meningitis cases: Staphylococcus coagulase-negative (n = 6), Klebsiella pneumoniae (n = 3), Acinetobacter baumannii (n = 3), Proteus mirabilis (n = 2), Staphylococcus aureus (n = 1), Klebsiella oxytoca (n = 1), Serratia marcescens (n = 1), Streptococcus viridans (n = 1), and Enterobacter cloacae (n = 1). The highest CSF lactate levels (> 3.5 mmol/L) were associated with a positive culture for bacteria in 31.58% of the CSF samples in which the causal bacteria were identified.

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Figure 3
Dynamics of the cerebrospinal fluid (CSF) lactate concentration (mmol/L) in patients with multibacterial meningitis, according to outcome. The continuous line indicates the positive-outcome (survival) group; the dashed line indicates the negative-outcome (death) group. The full circle indicates the CSF sample with positive cultures for bacteria different from that isolate from the first CSF sample. Bacteria identified in multibacterial meningitis cases: Staphylococcus coagulase-negative (n = 6), Klebsiella pneumoniae (n = 3), Acinetobacter baumannii (n = 3), Proteus mirabilis (n = 2), Staphylococcus aureus (n = 1), Klebsiella oxytoca (n = 1), Serratia marcescens (n = 1), Streptococcus viridans (n = 1), and Enterobacter cloacae (n = 1). The highest CSF lactate levels (> 3.5 mmol/L) were associated with a positive culture for bacteria in 31.58% of the CSF samples in which the causal bacteria were identified.

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Table 1
Bacteria identified in cultures of the first cerebrospinal fluid (CSF) sample.

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Table 2
Cerebrospinal fluid (CSF) xanthochromia, cytological, and biochemical characteristics of the first and last CSF samples, by outcome.

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Table 3
Dynamics of cerebrospinal fluid (CSF) xanthochromia, and cytological and biochemical characteristics evaluated according to the mean of all longitudinal CSF samples for the same participant, as well as variation between the first and last sample for each participant by outcome.

Bacteria	Total	Survival	Death	p-value
Staphylococcus coagulase negative	12 (24.49)	10 (25.0)	2 (22.22)	0.999
Streptococcus pneumoniae	9 (18.37)	8 (20.00)	1 (11.11)	0.999
Staphylococcus aureus	8 (16.33)	6 (15.00)	2 (22.22)	0.638
Klebsiella pneumoniae	5 (10.20)	3 (7.50)	2 (22.22)	0.224
Enterobacter spp.	5 (10.20)	4 (10.00)	1 (11.11)	0.999
Acinetobacter baumannii	2 (4.08)	2 (5.00)	–	–
Escherichia coli	2 (4.08)	2 (5.00)	–	–
Haemophilus influenzae	1 (2.08)	1 (2.08)	–	–
Proteus mirabilis	1 (2.08)	–	1 (11.11)	–
Pseudomonas stutzeri	1 (2.08)	1 (2.50)	–	–
Staphylococcus haemolyticus	1 (2.08)	1 (2.50)	–	–
Streptococcus viridans group	1 (2.08)	1 (2.50)	–	–
Bacilli Gram-negative, oxidase-negative	1 (2.08)	1 (2.50)	–	–

Variable		First puncture				Last puncture				p-value⁴ 4 Wilcoxon's test between the first and last CSF sample, total group;	p-value⁵ 5 Wilcoxon's test between the first and last CSF sample of the survival group:	p-value⁵ 5 Wilcoxon's test between the first and last CSF sample of the survival group:
Variable		Total	Survival	Death	p-value	Total	Survival	Death	p-value
n (%)		49 (100)	40 (81.63)	9(18.37)		36	30(83.33)	6(16.67)
Color index (%)¹ 1 43 samples with color index in the first CSF sample (survival: 35; death: 8); and 42 in the last CSF sample (survival: 34; death: 8);		0.3(0:0.75)	0.3 (0; 1)	0.5(0:25.37)	0.483	0.2(0; 0.5)	0(0; 0.5)	0.5(0.35:0.87)	0.034	0.591	0.735	0.813
	Color index > 0% (n %)	25(58.14)	20(57.14)	5(62.50)	1.000	25(83.33)	17 (70.83)	6(100)	0.068	0.353	0.632	0.209
RBC (cells/mm³)		320(144:1565)	295(104.75:1035)	510(225:10900)	0.653	112 (10.12:697.5)	112 (7.97:597.5)	98(20.25:602.5)	0.832	0.144	0.145	0.776
WBC (cells/mm³)		67 (5.3:450)	117.5(5:1148.75)	13(2.8:68.7)	0.131	24.25(9.25:112)	23.75(9.15:69.75)	610.5(19:1342)	0.959	0.137	0.018	0.156
WBC > 5 cells/mm³ (n %)		37 (75.51)	30(75.00)	7 (77.78)	1.000	32 (88.89)	27 (90.00)	5(83.33)	0.535	0.163	0.132	0.999
Neutrophils (%)² 2 35 samples with differential cell count in the first CSF sample (survival: 29; death: 6), and 38 in the last CSF sample (survival: 33; death: 5);		83 (61.5:92.5)	83 (74; 94)	24(7.75:72.5)	0.168	15(2.5;58)	10(1.5;30)	91.5(69.25:94.25)	0.014	0.009	< 0.001	–
Lymphocytes (%)² 2 35 samples with differential cell count in the first CSF sample (survival: 29; death: 6), and 38 in the last CSF sample (survival: 33; death: 5);		14(4.25:30.25)	12 (4; 23)	71 (46; 87)	0.025	69.5(42.5:89.75)	70(50.5:90.5)	5 (3; 43)	0.041	0.005	< 0.001	–
Neutrophil/lymphocyte ratio		5.70(2.27:20.75)	7.33 (3.15;27.71)	0.37 ⁷ 7 maximum, minimum; (0.01; 9.78)	0.020	0.237(0.075:1.415)	0.209 (0.045:0.506)	18.60 ⁷ 7 maximum, minimum; (0.09; 98)	0.157	0.058	0.0005	–
Glucose (mg/dL)		32(5:61)	28.5(5:53.75)	85(25;104)	0.032	42 (27.75;51)	45 (30; 53)	28(21.75:34.25)	0.301	0.697	0.075	0.063
	Glucose < 45 mg/ dL(n %)	31 (63.26)	27 (67.50)	4 (44.44)	0.259	20(55.56)	15(50.00)	5(83.33)	0.196	0.508	0.150	0.287
	Glucose CSF/ blood³ 3 25 samples with blood glucose on the date of the first CSF sample (survival: 21; death: 4); and 14 in the last CSF sample (survival: 11; death: 3);	0.51 (0.05:0.6)	0.48 (0.05:0.58)	0.61 (0.44;0.65)	0.394	0.09(0.02:0.55)	0.11 (0.04;0.53)	0.02(0.01:0.33)	0.754	1.125	0.500	0.999
	Glucose CSF/ blood < 0.4 (n %)	10(40.00)	10 (47.61)	1 (25.00)	0.615	9(64.29)	7 (63.63)	2 (66.67)	0.999	0.191	0.472	0.486
Total protein (mg/dL)		89.5(34.9:356.6)	89.4(35.27:346.02)	165.2 (29.7:768.6)	0.767	109.85 (51.8:228.8)	93.25(49.4:174.87)	232 (162:295)	0.048	0.866	0.647	0.844
	Total protein increased (n%)⁸ 8 Total protein increased in accordance with reference values by location of CSF puncture: ventricular 5-15 mg/dL, sub-occipital 10-25 mg/dL, and lumbar 15-45 mg/dL[5]; analyzed with Fisher's exact test.	45 (92)	38 (95)	7(78)	0.149	34 (94)	28(93)	6(100)	0.999	0.999	0.999	0.486
Lactate (mmol/L)		4.7 (2.2; 10.7)	4.9(2.17:10.95)	3.4 (2.5; 5.4)	0.938	2.75(1.97:4.37)	2.45(1.9:3.57)	6.75(4.8:7.5)	0.002	0.014	< 0.001	0.031
Lactate >3.5 mmol/L (n %)		27 (55.10)	23 (57.50)	4 (44.44)	0.713	13(36.11)	8(26.67)	5(83.33)	0.016	0.123	0.015	0.287
Normal (n %)		5(10.20)	4(10)	1 (11.11)	1.00	1 (2.78)	1 (3.33)	0	0.999	0.236	0.383	0.999

Variables	Variation between first and last CSF puncture				Mean of all CSF punctures
Variables	Total	Survival	Death	p-value	Total	Survival	Death	p-value
n (%)	36(100)	30(83.33)	6(16.67)		36(100)	30(83.33)	6(16.67)	–
Number of punctures	–	–	–	–	4(1:6)	4(1.75:6)	2(1:5)	–
Color index (%)¹ 1 31 samples with color index in the first and last CSF sample, (survival: 25; death: 6);	0 (-0.15; 0.5)	0(0; 0.5)	-0.15 (-0.82; 74.62)	0.409	2(0.1:0.78)	0.3 (0.1:0.71)	0.5(0.5:0.86)	0.047
Color index > 0 % (n %)	–	–	–	–	32 (86.11)	26(86.67)	6(100)	0.999
WBC (cells/mm³)	15.9 (-15.57; 305.95)	27.9 (-7.37; 1237.82)	-274.1 (-1026.2;-13.4)	0.017	142.23 (47.5:598.75)	138.34(4.18:575.06)	195.33(100:604.2)	0.708
WBC > 5 cells/mm³ (n %)	–	–	–	–	35(97.22)	30(100)	5(83.33)	0.167
Neutrophils (%)² 2 26 samples with differential cell count in the first and last CSF sample (survival: 21; death: 5); and 33 patients in more than one CSF sample (survival: 28; death: 5);	56(11.25:84.25)	65(20:87)	1 (-67; 10)	0.074	57 (35.4:72)	56.2 (35; 74)	61.37(49.09:63.96)	0.925
Lymphocytes {%)² 2 26 samples with differential cell count in the first and last CSF sample (survival: 21; death: 5); and 33 patients in more than one CSF sample (survival: 28; death: 5);	-29.5 (-78.5; 4.75)	-59 (-80;-9)	66 (46;86)	0.010	35.43 (18.25;50)	35.43(17.4.51.14)	34.9(31.31:43.89)	0.839
Glucose (mg/dL)	-4 (-21.5;18.75)	-8 (-24.5; 2.75)	45(21.25:71.75)	0.006	30.17 (18.5:54.06)	32.87 (15.17;53.13)	28.5(25.67:57.5)	0.290
Glucose < 45 mg/dL (n %)	–	–	–	–	21 (58.33)	18(60.00)	3 (50.00)	0.677
Glucose CSF/blood³ 3 4 patients with blood glucose test performed on the date of the first and last puncture (survival: 4. death: 0); 23 patients had blood glucose test performed on the same date as CSF sampling for more than one CSF sample (survival: 18; death: 5).	-0.43 (-0.57;-0.22)	-0.43 (-0.57;-0.22)	–	0.500	0.34(0.06:0.55)	0.36(0.07:0.54)	0.32(0.05:0.55)	0.999
Glucose CSF/blood < 0.4 (n %)	–	–	–	–	12 (52.17)	9(50.00)	3 (60.00)	0.999
Total protein (mg/dL)	3.65 (-93.82:90.97)	4.4 (-65.1; 71.9)	-87.65 (-180.75:87.72)	0.291	144.27(60.9:266.4)	118.91 (48.93:280.76)	171.95(131.43:195.85)	0.446
Lactate (mmol/L)	1.45 (-0.55:4.3)	2.15 (-0.15;4.97)	-3.15 (-5.62;-0.9)	<0.001	4.94(2.85:7.5)	4.05(2.76:7.39)	5.61 (5.15; 10.07)	0.091
Lactate > 3.5 mmol/L (n %)	–	–	–	–	23 (63.89)	18(60.00)	5(83.33)	0.634

[1] Correspondence: Sérgio Monteiro de Almeida; Hospital de Clínicas, UFPR, Seção de Virologia, Setor Análises Clínicas; Rua Padre Camargo, 280; 80060-240 Curitiba PR, Brasil; E-mail: sergio.ma@ufpr.br

Brasil

Brasil

Comparison of cerebrospinal fluid lactate with physical, cytological, and other biochemical characteristics as prognostic factors in acute bacterial meningitis

Comparação do lactato no líquido cefalorraquidiano com as características físicas, citológicas e outros marcadores bioquímicos, como fator prognostico nas meningites bacterianas agudas

ABSTRACT

Objective:

Methods:

Results:

Conclusion: