Multidrug-Resistant Infections Among Hospitalized Adults With Community-Acquired Pneumonia In An Indonesian Tertiary Referral Hospital

Figures & data

Table 1 Indonesian Guideline For CAP Patients

Patient Care	The Strategies:
Wards	One of the following options: Beta-lactam iv + beta-lactamase inhibitor iv The second and third generation of cephalosporins iv Respiratory fluoroquinolone iv Macrolide (additional antibiotic when atypical infections identified)
Intensive care	No pseudomonal infection: The third-generation of cephalosporin iv + macrolide When a pseudomonal infection presents, one of the following options: Anti-pseudomonal cephalosporin iv Carbapenem iv + anti-pseudomonal antibiotic iv Aminoglycoside iv If there is an atypical infection, using the following three-drug combination: Anti-pseudomonal cephalosporin iv (or carbapenem iv) + macrolide (or respiratory fluoroquinolone iv) + aminoglycoside iv

Note: Adapted from Indonesian Society of Respirology. Guideline for diagnosis and management of community pneumonia in Indonesia[Perhimpunan Dokter Paru Indonesia. Pneumonia komuniti: pedoman diagnosis & penatalaksanaan di Indonesia]. 2003. Available: http://www.klikpdpi.com/konsensus/konsensus-pneumoniakom/pnkomuniti.pdf.²⁰

Table 2 Etiology Characteristics (n=202 Isolates)

Bacterial Agents	N	Percentage	Blood Culture	Sputum Culture	MDR-CAP
Single-agent
A. baumannii	27	13.4		27	13
Enterobacter spp	10	5.0		10	3
E. coli	10	5.0		10	1
K. pneumoniae	25	12.4		25	9
P. aeruginosa	18	8.9		18	8
S. aureus	9	4.5		9	2
S. non-haemolyticus	4	2.0		4
S. pneumoniae	26	12.9		26	1
S. viridans	31	15.3		31
Mixed-agents
A. baumannii	1	0.5	1
+ M. tuberculosis	1	0.5		1
Enterobacter spp	1	0.5	1		1
+ H. influenzae	1	0.5		1
K. pneumoniae	1	0.5	1		1
+ M. tuberculosis	1	0.5		1
K. pneumoniae	1	0.5	1		1
+ H. influenzae	1	0.5		1
P. aeruginosa	1	0.5		1	1
+ Pantoe agglomerans	1	0.5	1
S. pneumoniae	1	0.5		1
+ Cronobacter sakazakii	1	0.5		1
S. pneumoniae	4	2.0		4
+ H. influenzae	4	2.0		4
S. pneumoniae	4	2.0		4	1
+ M. tuberculosis	4	2.0		4
S. pneumoniae	2	1.0		2
+ Staphyloccus spp (coagulase negative)	2	1.0		2
S. viridans	2	1.0		2	1
+ M. tuberculosis	2	1.0		2
S. viridans	3	1.5		3	1
+ H. influenzae	3	1.5		3

Table 3 Antibiotic Susceptibility Pattern Among CAP Associated Pathogens

Bacteria	AMK, n(%)	GEN, n(%)	AMC, n(%)	SAM, n(%)	TIC, n(%)	PIP, n(%)	CFZ, n(%)	CAZ, n(%)	CTX, n(%)	CRO, n(%)	CFP, n(%)	SXT, n(%)	CIP, n(%)	LVX, n(%)	MXF, n(%)	IPM, n(%)	MEM, n(%)	VAN, n(%)
A. baumannii (n=28)
S	23 (82.1)	22 (78.6)	3 (10.7)	15 (53.6)	5 (17.9)	12 (42.9)	8 (28.6)	15 (53.6)	13 (46.4)	15 (53.6)	26 (92.9)	20 (71.4)	6 (21.4)	17 (60.7)	13 (46.4)	14 (50.0)	21 (75.0)	NA
I	0	1 (3.6)	0	0	8 (28.6)	3 (10.7)	5 (17.9)	2 (7.1)	1 (3.6)	3 (10.7)	0	0	5 (17.9)	0	12 (42.9)	4 (14.3)	1 (3.6)	NA
R	5 (17.9)	5 (17.9)	25 (89.3)	13 (46.4)	15 (53.6)	13 (46.4)	15 (53.6)	11 (39.3)	14 (50.0)	10 (35.7)	2 (7.2)	8 (28.6)	17 (60.7)	11 (39.3)	3 (10.7)	10 (35.7)	6 (21.4)	NA
E. coli (n=10)
S	8 (80.0)	9 (90.0)	6 (60.0)	3 (30.0)	2 (20.0)	6 (60.0)	4 (40.0)	8 (80.0)	8 (80.0)	7 (70.0)	9 (90.0)	7 (70.0)	6 (60.0)	7 (70.0)	7 (70.0)	8 (80.0)	9 (90.0)	NA
I	0	0	0	2 (20.0)	2 (20.0)	0	2 (20.0)	0	1 (10.0)	0	0	1 (10.0)	1 (10.0)	1 (10.0)	2 (20.0)	2 (20.0)	0	NA
R	2 (20.0)	1 (10.0)	4 (40.0)	5 (50.0)	6 (60.0)	4 (40.0)	4 (40.0)	2 (20.0)	1 (10.0)	3 (30.0)	1 (10.0)	2 (20.0)	3 (30.0)	2 (20.0)	1 (10.0)	0	1 (10.0)	NA
Enterobacter. spp (n=11)
S	10 (90.9)	9 (81.8)	2 (18.2)	2 (18.2)	5 (45.5)	7 (63.6)	2 (18.2)	8 (72.7)	7 (63.6)	8 (72.7)	10 (90.9)	6 (54.5)	7 (63.6)	10 (90.9)	4 (36.4)	7 (63.6)	10 (90.9)	NA
I	0	0	0	0	3 (27.3)	1 (9.1)	0	2 (18.2)	0	0	0	1 (9.1)	1 (9.1)	0	5 (45.5)	2 (18.2)	0	NA
R	1 (9.1)	2 (18.2)	9 (81.8)	9 (81.8)	3 (27.3)	3 (27.3)	9 (81.8)	1 (9.1)	4 (36.4)	3 (27.3)	1 (9.1)	4 (36.4)	3 (27.3)	1 (9.1)	2 (18.2)	2 (18.2)	1 (9.1)	NA
K. pneumoniae (n=27)
S	25 (92.6)	22 (81.5)	7 (25.9)	7 (25.9)	6 (22.2)	16 (59.3)	11 (40.7)	17 (63.0)	18 (66.7)	18 (66.7)	22 (81.5)	21 (77.8)	8 (29.6)	21 (77.8)	17 (63.0)	19 (70.4)	22 (81.5)	NA
I	0	0	1 (3.7)	1 (3.7)	7 (25.9)	1 (3.7)	2 (7.4)	2 (7.4)	0	0	1 (3.7)	3 (11.1)	2 (7.4)	0	7 (25.9)	3 (11.1)	1 (3.7)	NA
R	2 (7.4)	5 (18.5)	19 (70.4)	19 (70.4)	14 (51.9)	10 (37.0)	14 (51.9)	8 (29.6)	9 (33.3)	9 (33.3)	4 (14.8)	3 (11.1)	17 (63.0)	6 (22.2)	3 (11.1)	5 (18.5)	4 (14.8)	NA
P. aeruginosa (n=19)
S	14 (73.7)	13 (68.4)	2 (10.5)	4 (21.1)	5 (26.3)	9 (47.4)	6 (31.6)	16 (84.2)	11 (57.9)	10 (52.6)	15 (78.9)	8 (42.1)	7 (36.8)	13 (68.4)	9 (47.4)	12 (63.2)	17 (89.5)	NA
I	0	0	0	0	5 (26.3)	2 (10.5)	3 (15.8)	1 (5.3)	0	1 (5.3)	0	1 (5.3)	3 (15.8)	0	7 (36.8)	3 (15.8)	0	NA
R	5 (26.3)	6 (31.6)	17 (89.5)	17 (89.5)	9 (47.4)	8 (42.1)	10 (52.6)	2 (10.5)	8 (42.1)	8 (42.1)	4 (21.1)	10 (52.6)	9 (47.4)	6 (31.6)	3 (15.8)	4 (21.1)	2 (10.5)	NA
S. aureus (n=9)
S	NA	NA	5 (55.6)	7 (77.8)	8 (88.9)	5 (55.6)	8 (88.9)	7 (77.8)	6 (66.7)	6 (66.7)	7 (77.8)	8 (88.9)	1 (11.1)	7 (77.8)	7 (77.8)	5 (55.6)	5 (55.6)	9 (100)
I	NA	NA	1 (11.1)	0	0	1 (11.1)	0	0	1 (11.1)	2 (22.2)	0	0	3 (33.3)	1 (11.1)	2 (22.2)	3 (33.3)	3 (33.3)	0
R	NA	NA	3 (33.3)	2 (22.2)	1 (11.1)	3 (33.3)	1 (11.1)	2 (22.2)	2 (22.2)	1 (11.1)	2 (22.2)	1 (11.1)	5 (55.6)	1 (11.1)	0	1 (11.1)	1 (11.1)	0
S. pneumoniae (n=37)
S	NA	NA	26 (70.3)	26 (70.3)	27 (73.0)	30 (81.1)	26 (70.3)	26 (70.3)	28 (75.7)	30 (81.1)	26 (70.3)	28 (75.7)	27 (73.0)	30 (81.1)	27 (73.0)	32 (86.5)	35 (94.6)	9 (100)
I	NA	NA	2 (5.3)	2 (5.3)	4 (10.8)	2 (5.4)	2 (5.3)	3 (8.1)	3 (8.1)	2 (5.4)	4 (10.8)	0	2 (5.4)	0	4 (10.8)	2 (5.3)	2 (5.3)	0
R	NA	NA	9 (24.3)	9 (24.3)	6 (16.2)	5 (13.3)	9 (24.3)	8 (21.6)	6 (16.2)	5 (13.5)	7 (18.9)	9 (24.3)	8 (21.6)	7 (18.9)	6 (16.2)	3 (8.1)	0	0
S. viridans (n=36)
S	NA	NA	15 (41.7)	20 (55.6)	28 (77.8)	27 (75.0)	26 (72.2)	27 (75.0)	27 (75.0)	29 (80.6)	30 (83.3)	25 (69.4)	23 (63.9)	30 (83.3)	22 (61.1)	29 (80.6)	30 (83.3)	9 (100)
I	NA	NA	8 (22.2)	8 (22.2)	4 (11.1)	4 (11.1)	8 (22.2)	6 (16.7)	5 (13.9)	4 (11.1)	4 (11.1)	1 (2.8)	7 (19.4)	0	6 (16.7)	4 (11.1)	4 (11.1)	0
R	NA	NA	13 (36.1)	8 (22.2)	4 (11.1)	5 (13.9)	2 (5.6)	3 (8.3)	4 (11.1)	3 (8.3)	2 (5.6)	10 (27.8)	6 (16.7)	6 (16.7)	8 (22.2)	3 (8.3)	2 (5.6)	0
All organisms (n=181)
S	80 (84.2)^a	75 (78.9)^a	66 (36.5)	86 (47.5)	90 (49.7)	116 (64.1)	95 (52.5)	128 (70.7)	122 (67.4)	127 (70.2)	149 (82.3)	123 (68.0)	85 (47.0)	137 (75.7)	108 (59.7)	126 (69.6)	149 (82.3)	86 (100)^b
I	0^a	1 (1.1)^a	16 (8.8)	15 (8.3)	33 (18.2)	14 (7.7)	22 (12.2)	16 (8.8)	12 (6.6)	11 (6.1)	9 (5.0)	8 (4.4)	28 (15.5)	2 (1.1)	47 (26.0)	27 (14.9)	15 (8.3)	0^b
R	15 (15.8)^a	19 (20.0)^a	99 (54.7)	80 (44.2)	58 (32.0)	51 (28.2)	64 (35.4)	37 (20.4)	47 (26.0)	43 (23.8)	23 (12.7)	50 (27.6)	68 (37.6)	42 (23.2)	26 (14.4)	28 (15.5)	17 (9.4)	0^b

Notes: ^aAmong 95 Gram-negative isolates including A. baumannii, E. coli, Enterobacter. spp, K. pneumoniae, and P. aeruginosa. ^bAmong 86 Gram-positive isolates including S. aureus, S. pneumoniae, S. viridans, and Staphylococcus non-haemolyticus.

Abbreviations: AMC, amoxicillin-clavulanate; AMK, amikacin; CAZ, ceftazidime; CFP, cefoperazone; CFZ, cefazolin; CIP, ciprofloxacin; CRO, ceftriaxone; CTX, cefotaxime; GEN, gentamycin; I, intermediate; IPM, imipenem; LVX, levofloxacin; MEM, meropenem; MXF, moxifloxacin; NA, not applicable; PEN, Penicillin; PIP, piperacillin-tazobactam; R, resistant; S, sensitive; SAM, ampicillin-sulbactam; SXT, trimethoprim-sulfamethoxazole; TIC, ticarcillin-clavulanate; VAN, vancomycin.

Figure 1 Resistance, intermediate, and sensitivity rates of multidrug-resistant agents causing hospitalized community-acquired pneumonia.

Table 4 Comparisons Of Clinical Characteristics Between Non-MDR and MDR

Clinical Characteristics	All Patients (n=181)	Non-MDR (n=137)	MDR (n=44)	p-Value
Gender
Male, n (%)	117(64.6)	84(61.3)	33(75.0)	0.099
Female, n (%)	64(35.4)	53(38.7)	11(25.0)
Age (years), mean (SD)	56.5(12.8)	55.7(12.6)	59.0(13.5)	0.157
Chief complaints at hospital admission
Fever, n (%)	174(96.1)	130(94.9)	44(100.0)	0.137
Cough, n (%)	133(73.5)	100(75.2)	33(24.8)	0.793
Dyspnea, n (%)	178(98.3)	134(97.8)	44(100.0)	0.431
Chest discomfort, n (%)	38(21.0)	26(19.0)	12(27.3)	0.240
RR (/min), median (P25-P75)	26(22–28)	24(22–28)	26(22.5–28)	0.210
Body temperature (°C), median (P25-P75)	37.0(36.7–37.8)	37.0(36.7–37.8)	37.0(36.7–37.7)	0.756
Blood leucocytes (per mm^3), median (P25-P75)	14,865(11,450–18,650)	15,000(11,500–18,200)	14,075(11,155–19,700)	0.750
SBP (mmHg), median (P25-P75)	120(110–130)	110(110–130)	120(110–140)	0.253
DBP (mmHg), median (P25-P75)	70(70–80)	70(70–80)	75(70–80)	0.929
Arterial blood gas
pH, median (P25-P75)	7.44(7.40–7.49)	7.44(7.40–7.49)	7.43(7.39–7.50)	0.721
pCO2 (mmHg), median (P25-P75)	36.0(31.0–45.7)	37.0(31.0–47.0)	35.0(30.6–39.6)	0.149
pO2 (mmHg), median (P25-P75)	76.1(67.0–98.4)	78.0(68.0–101.5)	76.0(61.0–95.7)	0.152
Base excess, median (P25-P75)	1.1(−2.0–5.8)	1.8(−1.8 to 6.0)	0.3(−3.3 to 4.5)	0.192
HCO3, median (P25-P75)	25.2(22.2–30.3)	25.7(22.4–30.5)	24.9(21.7–28.6)	0.292
SO2, median (P25-P75)	96.0(94.0–98.1)	96.0(94.0–98.1)	96.3(92.2–98.3)	0.509
Pleural effusion, n (%)	26(14.4)	19(13.9)	7(15.9)	0.737
Co-morbidities
Cardiovascular diseases, n (%)	21(11.6)	15(10.9)	6(13.6)	0.628
Neoplasm, n (%)	46(25.4)	24(17.5)	22(50.0)	<0.001*
Diabetes mellitus, n (%)	51(28.2)	33(24.1)	18(40.9)	0.031*
Hepatic disorder, n (%)	13(7.2)	9(6.6)	4(9.1)	0.392
Renal insufficiency, n (%)	31(17.1)	22(16.1)	9(20.5)	0.501
PSI class
Class I, n (%)	14(7.7)	13(9.5)	1(2.3)	0.003*
Class II, n (%)	22(12.2)	20(14.6)	2(4.5)
Class III, n (%)	84(46.4)	68(49.6)	16(36.4)
Class IV, n (%)	48(26.5)	29(21.2)	19(43.2)
Class V, n (%)	13(7.2)	7(5.1)	6(13.6)
Intensive care	28(15.5)	18(64.3)	10(22.7)	0.126
Empirical antibiotics
Ceftazidime, n (%)	56(30.9)	44(32.1)	12(27.3)	0.506
Ceftriaxone, n (%)	75(41.4)	63(46.0)	12(27.3)
Levofloxacin, n (%)	20(11.0)	15(10.9)	5(11.4)
Ceftazidime + levofloxacin, n (%)	16(8.8)	9(6.6)	7(15.9)
Ceftriaxone + levofloxacin, n (%)	14(7.7)	6(4.4)	8(18.2)
Clinical follow-up
Length of stay, median (P25-P75)	12.0(8.0–16.0)	11.5(8.0–15.8)	12.6(9.0–16.4)	0.374
Day-3 improvement, n (%)	81(44.8)	76(55.5)	5(11.4)	<0.001*
14-day mortality rates, n (%)	55(30.4)	30(21.9)	25(56.8)	<0.001*

Note: *Statistically significant, p-value < 0.05.

Abbreviations: DBP, diastolic blood pressure; max, maximum; med, median; min, minimum; MDR, multidrug-resistant; PSI, pneumonia severity index; RR, respiratory rate; SBP, systolic blood pressure.

Table 5 Multivariate Analysis Of Risk Factors For Mortality Among CAP Patients

Variable	CAP Mortality		Univariate Analysis			Multivariate Analysis
	No (n=126)	Yes (n=55)	OR	95% CI	p-value	aOR	95% CI	p-value
Host factors
Male	82(65.1)	35(63.6)	0.939	0.485–1.817	0.852	0.483	0.190–1.229	0.127
Age>60	40(31.7)	26(47.3)	1.928	1.008–3.688	0.047	1.482	0.585–3.751	0.407
Cardiovascular disease	9(7.1)	12(21.8)	3.628	1.428–9.216	0.007	2.401	0.684–8.422	0.171
Neoplasm	21(16.7)	25(45.5)	4.167	2.053–8.458	<0.001	2.755*	1.031–7.361	0.043
Diabetes mellitus	24(19.0)	27(49.1)	4.098	2.054–8.177	<0.001	2.098	0.780–5.642	0.142
Liver disease	7(5.6)	6(10.9)	2.082	0.666–6.509	0.208	3.800	0.633–22.810	0.144
Renal insufficiency	18(14.3)	13(23.6)	1.857	0.837–4.123	0.128	1.917	0.592–6.201	0.277
PSI class ≥3	92(73.0)	53(96.4)	9.793	2.262–42.407	0.002	9.188*	1.510–55.891	0.016
Day-3 improvement	77(61.1)	4(7.3)	0.050	0.017–0.147	<0.001	0.055*	0.016–0.190	<0.001
Agent factor
MDR-bacterial infections	19(15.1)	25(45.5)	4.693	2.282–9.651	<0.001	1.259	0.471–3.361	0.646
Treatment factor
Antibiotic combination	14(11.1)	16(29.1)	3.282	1.468–7.338	0.004	2.424	0.717–8.196	0.154

Note: *Statistically significant in multivariate analysis, the aOR CI95% does not include a value of 1.

Abbreviations: CAP, community-acquired pneumonia; MDR, multidrug resistance; OR, odds ratio; aOR, adjusted odds ratio; PSI, pneumonia severity index.

Adapted from Indonesian Society of Respirology. Guideline for diagnosis and man-agement of community pneumonia in Indonesia[Perhimpunan Dokter Paru Indonesia. Pneumonia komuniti: pedoman diagnosis & penatalaksanaan di Indonesia] 2003, page 13. Available from: http://www.klikpdpi.com/konsensus/konsensus-pneumoniakom/pnkomuniti.pdf Accessed October 7, 2019.

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