Download Infectious Myositis Secondary to Multidrug

Infectious Myositis Secondary to Multidrug-Resistant Gram Negative Rods in Cancer Patients
Nobuyoshi Mori, MD1, 2, Polly Williams, BS, MT(ASCP)1, Karen Vigil, MD2, Jeffrey Tarrand, MD1, Zhi-Dong Jiang, MD, PhD3,
Herbert DuPont, MD, FIDSA2, 3, Javier Adachi, MD, FIDSA1, 2, 3
1 The University of Texas MD Anderson Cancer Center, 2 The University of Texas Health Science Center at Houston Medical School,
3 The University of Texas Health Science Center at Houston School of Public Health
Abstract
Background: Severe infections caused by multidrug-resistant gram
negative rods (MDR-GNRs) are increasing healthcare problem worldwide,
especially in immunocompromised patients. Infectious myositis is a primary
infection of skeletal muscles, usually secondary to gram-positive bacteria,
especially Staphylococcus aureus. Although myositis secondary to GNRs
are uncommon, several cases secondary to Escherichia coli have been
reported in cancer patients.
Objectives: To describe the microbiological and clinical characteristics of
infectious myositis secondary to MDR-GNRs in cancer patients.
Methods: From January 2009 to December 2013 we retrospectively
reviewed clinical isolates to identify cases of myositis secondary to MDRGNRs. The diagnosis of infectious myositis was based on clinical
presentation (fever and/or pain in the involved muscle), confirmed by
compatible radiologic findings and/or muscle biopsy. MDR-GNRs were
defined by presence of ESBL or resistance to ≥ 3 of 4 groups (3rd-4th
generation cephalosporins, carbapenems, piperacillin/tazobactam and/or
quinolones). Resistance to carbapenems alone was also criteria for
Carbapenem-Resistant Enterobacteriaceae (CRE) and MDRPseudomonas.
Results: Seventeen cases of MDR-GNRs myositis were identified. Median
age was 51 y.o. (10 - 83), with 14:3 male to female ratio. All patients had
hematological malignancies (65% AML) and severe neutropenia, with 65%
involvement of lower extremities. E. coli (47%) was the leading cause,
followed by Klebsiella pneumoniae (24%), Enterobacter species (18%),
Pseudomonas aeruginosa (6%) and Stenotrophomonas maltophilia (6%).
Among 15 Enterobacteriacea isolates, 27% were CRE and 73% produced
ESBL. 88% were diagnosed based on positive blood culture and imaging
studies, and the remaining 12% were based on muscle biopsy. 82%
received active combination antimicrobial therapy, whereas 18% had active
single therapy. Only one patient (6%) expired.
Conclusion: Infectious myositis secondary to MDR-GNRs has emerged as
a serious problem among neutropenic patients with hematologic
malignancy. Awareness of this emerging infection and causative organisms
are essential to ensure early and appropriate therapy, to achieve the best
possible clinical outcome.
Materials and Methods
 Retrospective review of clinical isolates to identify cases of myositis
secondary to MDR-GNRs at University of Texas MD Anderson Cancer
Center (MDACC) from January 2009 to December 2013
 Diagnosis of infectious myositis was based on:
• Clinical presentation (fever and/or pain in the involved muscle) and
• Confirmation by compatible radiologic findings (edema and/or
inflammation in the muscle tissue by CT, MRI or ultrasound) and/or
• Muscle biopsy
 MDR-GNRs were defined as follows:
• Presence of ESBL (Extended-Spectrum-B-Lactamase);
• Resistance to carbapenems alone; or
• Resistance to 3 or more of the following antibiotics:
1. 3rd-4th generation cephalosporins
2. Carbapenems
3. Piperacillin/tazobactam
4. Fluoroquinolones
Results
 17 cases of infectious myositis secondary to MDR-GNRs
Table 1: Demographics
Background
Age, y, median (range)
51 (10 – 83)
Sex, male: female ratio
14 : 3
 Severe infections caused by multidrugresistant gram negative rods (MDR-GNRs) are
important healthcare problem worldwide,
especially in immunocompromised patients [13].
 Infectious myositis is a primary infection of
skeletal muscles, usually secondary to grampositive bacteria, especially Staphylococcus
aureus. [4-6]
 Although infectious myositis secondary to
GNRs are uncommon, several cases caused by
Escherichia coli have been reported in cancer
patients. [7]
Country, USA vs out of USA
14 : 3
Underlying malignancy
83 (100)
Objectives
 To describe the microbiological and clinical
characteristics of infectious myositis secondary
to MDR-GNRs in cancer patients.
Hematologic
17 (100)
Solid
0 (0)
Matched unrelated donor
6%
6%
6%
65%
5
AML
ALL
CML
Lymphoma
Myeloma
17%
3
2
1
0
< 14
14 to 30
> 60 days
30 to 60
• Duration (days), median (range): 38 (5 – 150)
• ANC nadir (/mm3), median (range): 0 (0 – 200)
Table 2: Clinical Manifestations
No. (%)
Fever
14 (82)
Muscle pain
17 (100)
Table 3: Diagnosis
No. (%)
Upper extremity
5 (30)
Lower extremity
10 (59)
Blood culture
15 (88)
Both extremities
1 (6)
Muscle biopsy
2 (12)
Others (neck)
1 (6)
Imaging study
16 (94)
Concomitant abscess
5 (30)
MRI
12 (71)
Sepsis*
9 (53)
CT
3 (18)
Severe sepsis**
8 (47)
Ultrasound
1 (6)
Figure 3: Microbiology
16%
25%
E. coli
P. aeruginosa
24%
E. cloacae
2
1
GvHD
1
S. maltophilia
35%
Table 4: Management
Neutropenia
16 (94)
Admission within 1 month prior to diagnosis
17 (100)
ID consult
17 (100)
Antibiotic use within 1 month prior to diagnosis
17 (100)
Active therapy
17 (100)
Corticosteroid use within 1 month prior to diagnosis
15 (88)
High dose
4 (24)
Low
11 (64)
17 (100)
11 (73%)
K. pneumoniae
ESBL
Carbapenem resistant enterobacteriacea (CRE)
No. (%)
Combination therapy
15 (88)
Single therapy
2 (12)
Duration, median (range)
28 (14 – 63)
Intervention
4 (80)
 Seventeen cases of MDR-GNRs myositis were identified.
 Median age was 51 (10 - 83), with 14:3 male to female ratio.
 All patients had hematological malignancies (65% AML) and 94%
had severe neutropenia, with 65% involvement of lower
extremities.
 E. coli (47%) was the leading cause, followed by Klebsiella
pneumoniae (24%), Enterobacter species (18%), Pseudomonas
aeruginosa (6%) and Stenotrophomonas maltophilia (6%). Among
15 Enterobacteriacea isolates, 27% were CRE and 73% produced
ESBL.
 88% were diagnosed based on positive blood culture and imaging
studies, and the remaining 12% were based on muscle biopsy.
30% had concomitant abscess formation.
 82% received active combination antimicrobial therapy, whereas
18% had active single therapy. Median duration of therapy was 28
days. Among 5 patients with abscess formation, 80% underwent
drainage or aspiration.
 Only one patient (6%) expired.
 Myositis secondary to MDR-GNRs has emerged as a serious
problem among neutropenic patients with hematologic
malignancy.
 Awareness of this emerging infection and causative
organisms are essential to ensure early and appropriate
therapy, improving the clinical outcome.
4 (27%)
6%
Results
Conclusions
Figure 3-1: Enterobacteriacea
3 (18)
Haploidentical
Central venous catheter insertion
4
*Sepsis: ≥2of: HR>90, RR>20, BT>38 or <36, WBC>1,2000 or <4000
**Severe sepsis: with hypotension responsive to fluid boluses
No. (%)
Stem cell transplant
Figure 2: Duration of neutropenia
Figure 1: Type of Cancer
Table 5: Outcome
No. (%)
Relapse within 3 months
0 (0)
Renal failure
4 (24)
ICU stay, infection-related
2 (12)
Drainage tube placement
1
Mortality, overall
1 (6)
Aspiration
3
Mortality, infection-related
1 (6)
Future Steps
 Perform virulence factor, molecular and genomic study to analyze
the risk factor for causing infectious myositis in cancer patients.
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