Clinical and Economic Impact of Common Multidrug-Resistant Gram-Negative Bacilli

Christian G. Giske; Dominique L. Monnet; Otto Cars; Yehuda Carmeli; on behalf of ReAct-Action on Antibiotic Resistance

doi:10.1128/AAC.01169-07

DOI: 10.1128/AAC.01169-07

Article Figures & Data

Tables

TABLE 1.

Prevalence of resistance to extended-spectrum cephalosporins in E. coli and K. pneumoniae in various parts of the world

Region	Period	Setting	Resistance (%)		Reference
Region	Period	Setting	K. pneumoniae	E. coli	Reference
North America
United States	2003	ICU	20.6	5.8	50
United States	2004	Intra-abdominal infections	5.3	2.8	63
United States (Brooklyn)	2006	All infections	59		40
Latin America
Seven countries	2000	Urinary tract infections	22.3	3.1	25
Ten countries	2004	Intra-abdominal infections	27.6	12.0	63
Europe
Northern Europe	2000-2001	Nosocomial infections	5.2	1.4	7
Southern Europe	2000-2001	Nosocomial infections	25.7	6.6	7
Nine countries	2004	Intra-abdominal infections	8.8	6.4	63
Asia
China	1998-2002	Nosocomial infections	37.3	31.3	30
Japan	1998-2002	Nosocomial infections	11.0	6.5	30
Singapore	1998-2002	Nosocomial infections	36.4	12.3	30
Oceania (Australia)	1998-2002	Nosocomial infections	4.6	1.6	30
South Africa	1998-2002	Nosocomial infections	29.6	1.9	30

TABLE 2.

Impact of extended-spectrum cephalosporin resistance in Enterobacteriaceae on mortality, LOS, and hospital cost

Type of study	Setting	Type of infection	Bacteria	No. of cases/no. of controls	Parameter	Main findings	Significance (P value or 95% CI)	Reference
Studies showing an impact of resistance
Case-control	Tertiary care	Nosocomial	E. coli and K. pneumoniae	33/66^a	LOS	Cases, 1.76 times greater duration	1.17-2.64	42
					Increased cost	Cases, 2.90 times higher cost	1.76-4.78
Case-control	Tertiary care	BSI	K. pneumoniae	44/118^a	LOS	Cases, 39.6 days; controls, 23.9 days	P < 0.008	38
Case-control	Multicenter	Nosocomial	K. pneumoniae	9/9	Mortality	Cases, 44%; controls, 33%	P > 0.05	9
					LOS	Cases, 37 ± 25 days; controls, 15 ± 10 days	P = 0.04
Case-control	Tertiary care	Peritonitis (CAPD^b)	E. coli	11/77	Mortality	Cases, 27.3%; controls, 3.9%	P = 0.02	83
Retrospective cohort	Tertiary care	BSI	Enterobacteriaceae	99/99^a	LOS	Cases, 1.56 greater duration	P = 0.001	68
					Increased cost	Cases, 1.57 times higher cost	P = 0.003
Retrospective cohort	Tertiary care	Non-urinary tract	E. coli and Klebsiella spp.	21/21^a	Mortality	Cases, 8%; controls, 14%	P = 0.182	44
					LOS	Cases, 21 days; controls, 11 days	P = 0.006
					Increased cost	Attributable cost, $16,450	$965-31,937
Retrospective cohort	Tertiary care	BSI	K. pneumoniae	46/82^a	Mortality	OR^c for death in cases, 2.66	1.07-6.59	76
					LOS	Cases, 22 days; controls, 16 days	P = 0.03
Prospective cohort	Tertiary care	BSI	E. coli	46/308^a	Mortality	OR for death in cases, 3.57	1.48-8.60	47
Studies showing no impact of resistance
Case-control	Tertiary care	Nosocomial	Enterobacteriaceae	23/174	Mortality	Cases, 26%; controls, 16%	P = 0.14	18
Case-control	Tertiary care	Nosocomial	K. pneumoniae	60/60^a, ^d	Mortality	Cases, 30%; controls, 28.3%	P = 0.0841	33
Case-control	Tertiary care	Nosocomial	Enterobacteriaceae	31/39	Mortality	Cases, 3.0%; controls, 2.4%	P > 0.05	13
Case-control	Tertiary care	BSI	E. coli and	35/105^a	LOS	Cases, 8.2 additional days	P = 0.182	84
			Klebsiella spp.
Retrospective cohort	Tertiary care	Nosocomial	K. pneumoniae	68/75^a	Mortality	RR^e, 0.94	0.45-1.97	28
Prospective cohort	Multicenter	BSI or pneumonia	Enterobacteriaceae	135/40	Mortality	Cases, 5.2%; controls, 12.5%	P = 0.15	4

↵ a Studies with either matched controls or multivariate analysis, in order to minimize confounding.
↵ b CAPD, continuous ambulatory peritoneal dialysis.
↵ c OR, odds ratio.
↵ d Matched controls.
↵ e RR, risk ratio.

TABLE 3.

Prevalence of MDR among P. aeruginosa strains in various parts of the world

Region	Period	Setting	Resistance (%)	Reference
North America
United States	2001	ICU/non-ICU	9.1/7.0	35
United States	2002	ICU	14	35
United States	2003	Nosocomial infections	9.9	36
South America, 10 sites	1997-1999	Nosocomial infections	8.2	24
Europe
12 to 23 sites	1997-1999	Nosocomial infections	4.7	24
33 ICUs	1997-2000	ICU	3-50	29
Asia/Pacific
17 sites	1997-1999	Nosocomial infections	1.6	24
Japan	2001	Nosocomial infections	2.8	74
Malaysia	2005	Nosocomial infections	6.9	62

TABLE 4.

Impact of the MDR phenotype in P. aeruginosa on mortality, LOS, and hospital cost

Type of study	Setting	Infection	No. of cases/no. of controls	Parameter	Main findings	Significance (P value or 95% CI)	Reference
Studies showing an impact of resistance
Case-control	Tertiary care	Nosocomial	69/247	Mortality	OR,^a 5.0	1.1-22.9	31
Retrospective cohort	Tertiary care	Nosocomial	44/68^b, ^c	Mortality	Cases, 54.5%; controls, 16.2%	P < 0.05	11
Case-control	Tertiary care	BSI	6/184^b, ^c	Mortality	Cases, 83.3%; controls, 36.4%	P = 0.03	34
Prospective	Tertiary care	Nosocomial/	98/103	Mortality	RR, 1.98	1.0-3.9	41
Prospective	Tertiary care	Nosocomial	86/212^c	Mortality	RR, 1.60	1.2-2.1^d	85
Retrospective matched cohort	Tertiary care	Nosocomial	82/82^b, ^c, ^e	Mortality	OR, 4.4	P = 0.04	1
Retrospective cohort study showing no impact of resistance	Tertiary care	Noscomial	18/35^c, ^f	Mortality	Cases, 22%; controls, 23%	P > 0.05	53

↵ a OR, odds ratio.
↵ b MDR was defined as resistance to four or more antibiotics.
↵ c Studies with either matched controls or multivariate analysis, in order to minimize confounding.
↵ d Not significant in multivariate analysis.
↵ e Matched controls.
↵ f MDR was defined as resistance to two or more antibiotics.

TABLE 5.

Prevalence of carbapenem resistance in Acinetobacter spp. in various parts of the world

Region	Period	Setting	Resistance (%)		Reference
Region	Period	Setting	Imipenem	Meropenem	Reference
North America
15 centers	2002-2004	Nonduplicate clinical isolates	8.3	6.5	78
24 centers	2001	Non-ICU isolates	6.1	10.4	35
15 centers	2006	All isolates	33	53	40
South America
25 centers	2002-2004	Nonduplicate clinical isolates	28.1	28.5	78
7 countries	2001	Nonduplicate clinical isolates	16.3	18.1	73
Europe
48 centers	2002-2004	Nonduplicate clinical isolates	30.2	26.9	78
37 centers	1997-2000	Nonduplicate clinical isolates	16	14	77
Asia/Pacific, 2 centers	2002-2004	Nonduplicate clinical isolates	1.2	6.0	78
Australia	1999-2004	Nonduplicate clinical isolates	11	11	78

TABLE 6.

Impact of carbapenem resistance in Acinetobacter spp. on mortality, LOS, and hospital costs

Type of study showing an impact of resistance	Setting	Infection	No. of cases/no. of controls	Parameter	Main findings	Significance (P value or 95% CI)	Reference
Case-control	Tertiary care	Nosocomial	10/10	Mortality	Cases, 34%; controls, 27%	P > 0.05	9
				LOS	Cases, 31.5 days; controls, 13 days	P = 0.02
Case-control	Tertiary care	Burn patients	34/43	Mortality	Cases, 26.5%; controls, 0%	P < 0.01	82
				LOS	Cases, 32.5 days; controls 21 days	P < 0.01
Case-control	Tertiary care	Burn patients	34/183	LOS	Cases, 36.8 days; controls, 25.6 days	P = 0.06	81
				Cost	Cases, $98,575 higher	P < 0.01
Case-control	Tertiary care	BSI	40/40^a	Mortality	Cases, 57.5%; controls, 25.7%	P = 0.007	39
Case-control	ICU	Nosocomial infections	34/68^a	Mortality	OR,^b 3.9	1.4-10.7	61
				LOS	Cases, 30 days longer	11-38 days
Case-control	ICU	Colonization	32/63^a	LOS (ICU)	Cases, 19 days longer	5-28 days	61