Proteus mirabilis Bloodstream Infections: Risk Factors and Treatment Outcome Related to the Expression of Extended-Spectrum β-Lactamases

Andrea Endimiani; Francesco Luzzaro; Gioconda Brigante; Mariagrazia Perilli; Gianluigi Lombardi; Gianfranco Amicosante; Gian Maria Rossolini; Antonio Toniolo

doi:10.1128/AAC.49.7.2598-2605.2005

DOI: 10.1128/AAC.49.7.2598-2605.2005

Article Figures & Data

Tables

TABLE 1.

MICs and molecular results for all P. mirabilis isolates causing BSI during the study period (January 1997 to June 2004)

Isolate	MIC of antimicrobial agent (μg/ml)^a																				Type of enzymes produced
Isolate	AMP	SAM	AMC	FOX	PIP	TZP	CRO	CTX	CTL	CAZ	TZL	FEP	IPM	MEM	ATM	CIP	LVX	AMK	GEN	TOB	Type of enzymes produced
43/97	>256	2	4	3	>256	0.75	3	8	0.032	2	0.064	4	1.5	0.125	0.125	4	4	4	96	16	TEM-52, TEM-1
1/98	>256	4	6	3	>256	0.5	4	8	0.032	2	0.064	4	3	0.064	0.094	>32	8	3	>256	6	TEM-52
405/01	>256	8	6	4	>256	0.5	3	8	0.032	4	0.250	3	0.5	0.094	0.38	>32	>32	4	>256	24	TEM-92
130/02	>256	2	6	2	>256	0.38	8	32	0.094	1	0.032	3	2	0.047	0.064	>32	16	3	>256	8	TEM-92, TEM-1
629/02	>256	8	12	4	>256	0.75	4	4	0.032	2	0.064	8	1	0.094	0.094	>32	>32	4	>256	24	TEM-92
139/03^b	>256	4	8	4	>256	0.5	4	8	0.032	2	0.064	32	1	0.064	0.125	>32	>32	4	>256	24	TEM-92
309/03^b	>256	4	8	4	>256	0.5	4	8	0.032	2	0.064	32	1	0.064	0.125	>32	>32	4	>256	24	TEM-92
463/03^b	>256	4	8	4	>256	0.5	4	8	0.032	2	0.064	32	1	0.064	0.125	>32	>32	4	>256	24	TEM-92
601/03	>256	2	4	4	>256	1	2	8	0.032	2	0.064	3	2	0.094	0.19	>32	>32	1.5	64	4	TEM-92, TEM-1
A19/03	>256	8	2	1.5	>256	0.75	2	4	0.032	2	0.064	2	2	0.047	0.047	0.75	2	3	96	8	TEM-92
A68/03	>256	4	4	6	>256	1	1.5	6	0.094	4	0.125	4	0.25	0.032	0.125	16	>32	1	64	4	TEM-92
65/99	>256	4	0.5	1	0.125	0.125	<0.016	<0.016	<0.016	<0.016	<0.016	0.064	0.5	0.023	<0.016	0.016	0.032	1.5	0.5	0.75	TEM-1
1289/01	>256	4	3	1.5	0.5	0.19	<0.016	<0.016	<0.016	<0.016	<0.016	0.047	0.75	0.032	<0.016	1	4	1.5	12	2	TEM-1
2501/01	0.5	0.5	0.38	2	0.125	0.125	<0.016	<0.016	<0.016	<0.016	<0.016	<0.016	1	0.032	<0.016	0.016	0.032	1	0.5	0.75	None
2512/01	0.5	0.5	0.38	1	0.125	0.125	<0.016	<0.016	<0.016	<0.016	<0.016	<0.016	0.5	0.032	<0.016	0.016	0.032	1	0.5	0.75	None
108/02	>256	8	1.5	1.5	0.5	0.19	<0.016	<0.016	<0.016	<0.016	<0.016	0.032	1	0.023	<0.016	0.016	0.032	2	1	0.5	TEM-1
461/02	0.5	0.5	0.38	1	0.125	0.125	<0.016	<0.016	<0.016	<0.016	<0.016	<0.016	0.75	0.032	<0.016	0.032	0.047	1.5	0.5	0.5	None
683/02	0.75	0.5	0.38	1	0.125	0.125	<0.016	<0.016	<0.016	<0.016	<0.016	0.094	1	0.032	<0.016	0.016	0.032	2	0.5	0.75	None
794/02	>256	2	0.5	1	0.125	0.125	<0.016	<0.016	<0.016	<0.016	<0.016	0.064	0.5	0.023	<0.016	0.016	0.032	6	128	32	TEM-1
85/03	1	1	0.38	1	0.125	0.125	<0.016	<0.016	<0.016	<0.016	<0.016	0.032	1	0.032	<0.016	0.016	0.032	1.5	4	8	None
654/03	>256	2	0.5	2	0.38	0.19	<0.016	<0.016	<0.016	<0.016	<0.016	0.032	0.75	0.032	<0.016	0.016	0.032	0.5	1	0.5	TEM-1
753/03	0.5	0.5	0.38	1	0.125	0.125	<0.016	<0.016	<0.016	<0.016	<0.016	<0.016	1	0.032	<0.016	0.016	0.032	2	0.5	0.75	None
A48/03	1	0.75	0.38	1	0.75	0.75	<0.016	<0.016	<0.016	<0.016	<0.016	<0.016	0.5	0.016	<0.016	0.016	0.032	1.5	2	1	None
134/04	>256	4	0.38	1	0.125	0.094	<0.016	<0.016	<0.016	<0.016	<0.016	0.047	1	0.032	<0.016	0.032	0.064	2	128	4	TEM-1
634/04	1	1	0.38	1	0.25	0.125	<0.016	<0.016	<0.016	<0.016	<0.016	0.023	1	0.032	<0.016	2	4	0.5	2	0.75	None

↵a Abbreviations for antimicrobial agents follow (NCCLS 2004 breakpoints for susceptibility [S] and resistance [R] [in micrograms per milliliter] are given in parentheses): AMP, ampicillin (S ≤ 8, R ≥ 32); SAM, ampicillin plus sulbactam (S ≤ 8/4, R ≥ 32/16); AMC, amoxicillin plus clavulanate (S ≤ 8/4, R ≥ 32/16); FOX, cefoxitin (S ≤ 8, R ≥ 32); PIP, piperacillin (S ≤ 16, R ≥ 128); TZP, piperacillin plus tazobactam (S ≤ 16/4, R ≥ 128/4); CRO, ceftriaxone (S ≤ 8, R ≥ 64); CTX, cefotaxime (S ≤ 8, R ≥ 64); CTL, cefotaxime plus clavulanate; CAZ, ceftazidime (S ≤ 8, R ≥ 32); TZL, ceftazidime plus clavulanate; FEP, cefepime (S ≤ 8, R ≥ 32); IPM, imipenem (S ≤ 4, R ≥ 16); MEM, meropenem (S ≤ 4, R ≥ 16); ATM, aztreonam (S ≤ 8, R ≥ 32); CIP, eiprofloxacin (S ≤ 1, R ≥ 4); LVX, levofloxacin (S ≤ 2, R ≥ 8); AMK, amikacin (S ≤ 16, R ≥ 32); GEN, gentamicin (S ≤ 4, R ≥ 8); TOB, tobramycin (S ≤ 4, R ≥ 8).
↵b These strains caused three different BSI in the same patient.

TABLE 2.

Demographic and clinical parameters of patients with BSI due to Proteus mirabilis strains and differences between ESBL-P-PM and ESBL-N-PM isolates

Demographic and clinical parameters	No. (%) of patients^a		P value^b
Demographic and clinical parameters	ESBL-P-PM	ESBL-N-PM	P value^b
No. of BSI patients	9^c	14	ND
No. of BSI episodes	11^c	14	ND
Age (yr) (mean ± SD)	70.9 ± 17.5	67.3 ± 18.2	NS
Sex (male/female)	7/2	7/7	ND
McCabe and Jackson groups^d
Nonfatal	5 (55.6)	8 (57.1)	NS
Ultimately fatal	3 (33.3)	4 (28.6)	NS
Rapidly fatal	1 (11.1)	2 (14.3)	NS
Charlson weighted index (mean ± SD)^e	4.0 ± 2.5	4.1 ± 2.6	NS
Severity of septicemia
Sepsis	6 (66.7)	11 (78.6)	NS
Severe sepsis	2 (22.2)	2 (14.3)	NS
Septic shock	1 (11.1)	1 (7.1)	NS
Previous hospitalizations (during the last 12 months)	6 (66.7)	8 (57.1)	NS
Previous hospitalization in nursing home	5 (55.6)	3 (21.4)	0.04
Hospital-acquired BSI	3 (33.3)	6 (42.9)	NS
Hospital stay before BSI diagnosis (days) (mean ± SD)	16.8 ± 30.3	6.0 ± 6.9	0.10
Length of hospital stay (days) (mean ± SD)	86.2 ± 193.4	19.4 ± 8.0	0.10
Empirical treatment
Provided	9 (100.0)	12 (85.7)	NS
Adequate	5 (55.6)	12 (85.7)	0.04
Adequate treatment after ID/AST results	4 (44.4)	12 (85.7)	0.04
Predisposing factors
Bladder catheter	9 (100.0)	8 (57.1)	0.01
Previous use of antibiotics	4 (44.4)	3 (21.4)	0.09
Intravascular catheter	4 (44.4)	3 (21.4)	0.09
Corticosteroids or antineoplastic therapy	2 (22.2)	4 (28.6)	NS
Previous surgery	0 (0.0)	3 (21.4)	NS
Drainages	0 (0.0)	3 (21.4)	NS
Intubation	1 (11.1)	1 (7.1)	NS
Secondary BSI
All patients	4 (44.4)	3 (21.4)	0.09
Urinary tract	4 (44.4)^f	3 (21.4)^g	0.09
Other	0 (0.0)	0 (0.0)	NS
Overall mortality	3 (33.3)	2 (14.3)	NS
Mortality attributable to BSI	3 (33.3)	0 (0.0)	0.04

↵a Data are number (%) of patients, unless otherwise indicated.
↵b NS, not significant; ND, not determined.
↵c One patient had three different BSI; therefore, statistical analysis was performed considering only 9 BSI patients.
↵d McCabe and Jackson groups used to classify the severity of the underlying disease (22).
↵e Comorbidity scores determined according to the Charlson weighted index (6).
↵f Three from bladder catheter.
↵g One from bladder catheter.

TABLE 3.

Clinical parameters, antimicrobial regimens, and treatment outcome of patients with BSI due to ESBL-N-PM and ESBL-P-PM strains

Isolate	Age (yr)	Sex^a	McCabe and Jackson group^b	Charlson weighted index^c	Severity of septicemia	Empirical antimicrobial treatment^d			Antimicrobial therapy administered after ID and AST results^d							Treatment outcome	Patient outcome and comments
Isolate	Age (yr)	Sex^a	McCabe and Jackson group^b	Charlson weighted index^c	Severity of septicemia							Agent (daily dose)	Adequate	Agent	Timing from BSI onset	Treatment outcome	Patient outcome and comments	Duration (days)	Daily dose
43/97 ESBL	83	F	Nonfatal	2	Sepsis	CRO (1,000 mg × 2)	No	CRO	4 days before	8	1,000 mg × 2	Partial response	Transferred on day 8 to nursing home
								GEN	First day	5	2,000 mg
1/98 ESBL	91	M	Nonfatal	3	Sepsis	CRO (1,000 mg)	No	N.c.	First day	6	N.c.	Failure	Death on day 6 for causes attributable to BSI
405/01 ESBL	43	M	Nonfatal	0	Sepsis	AMC (1,000 mg × 3)	Yes	N.c.	First day	9	N.c.	Relapse	Transferred on day 12 to clinic for rehabilitation
130/02 ESBL	77	M	Nonfatal	5	Sepsis	SAM (1,500 mg × 3)	Yes	MEM	3 days after	21	1,000 mg × 3	Complete response	Discharged on day 46
								AMK	3 days after	21	500 mg
629/02 ESBL	65	M	Rapidly	7	Sepsis	SAM (3,000 mg × 3)	Yes	N.c.	2 day before	6	N.c.	Failure	Death on day 4 for causes attributable to BSI
						AMK (500 mg × 3)
139/03 ESBL^e	45	M	Nonfatal	0	Sepsis	CRO (2,000 mg)	No	N.c.	First day	12	N.c.	Relapse	New BSI on day 12
309/03 ESBL^e	45	M	Nonfatal	0	Sepsis	CRO (1,000 mg × 2)	No	SAM	3 days after	12	1,500 mg × 4	Partial response	Recurrent UTI^f; new BSI on day 42
463/03 ESBL^e	45	M	Nonfatal	0	Sepsis	FEP (1,000 mg × 3)	No	N.c.	First day	10	N.c.	Failure	Complete response when AMK (500 mg × 2) added on day 53 for 6 days
601/03 ESBL	81	M	Ultimately	4	Septic shock	TZP (2,250 mg × 3)	Yes	N.c.	2 days before	6	N.c.	Failure	Death on day 4 for causes attributable to BSI
A19/03 ESBL	84	F	Ultimately	6	Severe sepsis	CAZ (2,000 mg × 3)	Yes	IPM	4 days after	12	1,000 mg × 3	Complete response	Transferred on day 21 to nursing home
						CIP (400 mg × 3)
A68/03 ESBL	71	M	Ultimately	7	Severe sepsis	CAZ (1,000 mg × 3)	No	CAZ	1 day before	13	2,000 mg × 2	Complete response	Discharged on day 13
								AMK	2 days after	10	500 mg × 2
65/99	77	F	Nonfatal	2	Sepsis	CRO (2,000 mg)	Yes	N.c.	1 day before	10	N.c.	Complete response	Transferred on day 11 to nursing home
1289/01	61	F	Rapidly	9	Sepsis	CRO (2,000 mg)	Yes	CIP	5 days after	9	400 mg × 3	Partial response	Complete response after IMP (1,000 mg × 3) use; death on day 24
2501/01	92	F	Ultimately	7	Severe sepsis	SAM (1,500 mg × 3)	Yes	N.c.	First day	9	N.c.	Complete response	Discharged on day 10
						AMK (500 mg)
2512/01	52	M	Rapidly	5	Sepsis	SAM (3,000 mg × 3)	Yes	N.c.	1 day before	8	N.c.	Complete response	Discharged on day 10
108/02	62	M	Nonfatal	2	Septic shock	IPM (1,000 mg × 4)	Yes	N.c.	10 days before	19	N.c.	Complete response	Discharged on day 90
						AMK (1,000 mg)
461/02	63	F	Ultimately	6	Severe sepsis	CRO (2,000 mg)	Yes	IPM	5 days after	8	1,000 mg × 2	Complete response	Discharged on day 26
						LVX (500 mg × 3)
683/02	16	M	Nonfatal	0	Sepsis	CRO (1,000 mg × 2)	Yes	N.c.	First day	6	N.c.	Complete response	Discharged on day 6
794/02	69	M	Nonfatal	5	Sepsis	None	No	IPM	1 day after	7	500 mg × 2	Complete response	Patient submitted to day hospital for dialysis
85/03	73	M	Nonfatal	2	Sepsis	TZP (2,250 mg × 3)	Yes	CAZ	2 days after	16	2,000 mg × 3	Complete response	Discharged on day 20
654/03	61	F	Ultimately	8	Sepsis	TZP (2,250 mg × 3)	Yes	N.c.	1 day before	15	N.c.	Complete response	Discharged on day 25
753/03	77	M	Nonfatal	3	Sepsis	TZP (2,250 mg × 3)	Yes	N.c.	1 day after	12	N.c.	Complete response	Discharged on day 8
A48/03	78	F	Nonfatal	2	Sepsis	CRO (2,000 mg)	Yes	N.c.	First day	7	N.c.	Complete response	Transferred on day 15 to clinic for rehabilitation
134/04	77	M	Ultimately	4	Sepsis	None	No	None	None	None	None	Not assessable	Death on day 1
634/04	84	F	Nonfatal	3	Sepsis	TZP (2,250 mg × 3)	N.c.	1 day before	9	N.c.	Complete response	Discharged on day 10

↵a F, female; M, male.
↵b McCabe and Jackson groups used to classify the severity of the underlying disease (22).
↵c Comorbidity scores determined according to the Charlson weighted index (6).
↵d Antimicrobial agent abbreviations: CRO, ceftriaxone; GEN, gentamicin; AMC, amoxicillin plus clavulanate; SAM, ampicillin plus sulbactam; MEM, meropenem; AMK, amikacin; FEP, cefepime; TZP, piperacillin plus tazobactam; CAZ, ceftazidime; CIP, ciprofloxacin; IPM, imipenem; LVX, levofloxacin. 1,000 mg × 2, two 1,000-mg doses. N.c., not changed.
↵e These cases occurred in the same patient.
↵f UTI, urinary tract infection.