CC BY-NC-ND 4.0 · Avicenna J Med 2019; 9(03): 107-110
DOI: 10.4103/ajm.AJM_189_18
BRIEF REPORT

Overprescription of antibiotics in patients with community-acquired pneumonia in the intensive care unit

Rorak Hooten
Department of Medicine, College of Medicine, University of Arizona, Tucson, AZ, USA
,
Jose Luis Marquez
Department of Medicine, College of Medicine, University of Arizona, Tucson, AZ, USA
,
Kady Goldlist
Department of Medicine, College of Medicine, University of Arizona, Tucson, AZ, USA
,
Rafael Urcis
Department of Medicine, College of Medicine, University of Arizona, Tucson, AZ, USA
,
Matthew Adams
Department of Medicine, College of Medicine, University of Arizona, Tucson, AZ, USA
,
Kathryn Matthias
Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ, USA
,
David Nix
Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ, USA
,
Mayar Al Mohajer
Department of Medicine, Baylor College of Medicine, Houston, TX, USA
› Author Affiliations
Financial support and sponsorship Nil.
 

Abstract

Purpose: We aimed to assess factors associated with therapy failure in patients with community-acquired pneumonia in the intensive care unit (ICU). Methods: Electronic charts of patients with International Classification of Diseases, Ninth Revision, codes of pneumonia who were admitted to the ICU at a tertiary academic medical center in Southern Arizona were reviewed. Results: Antipseudomonal coverage and anti-methicillin-resistant Staphylococcus aureus (MRSA) coverage were often prescribed (58.4% and 54.1%, respectively). Antipseudomonal coverage was rarely necessary as pseudomonal pneumonia was found in only one case (0.9%). Antipseudomonal and anti-MRSA coverage was not associated with improved outcomes. Conclusion: Overprescription of antibiotics in this population remains a significant problem. More work is needed to further limit unnecessary antibiotic use.


#

INTRODUCTION

Around 53–63% of patients with community-acquired pneumonia (CAP) are hospitalized every year.[1] There has been a growing concern for an increase in methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Traditionally MRSA was a concern for nosocomial pneumonia, but as the rate of MRSA has increased in the community setting, this organism is now starting to be seen in patients without risks for healthcare-associated pneumonia.[2],[3],[4] In addition, MRSA isolates carrying Panton–Valentine leukocidin genes were associated with severe pneumonia resulting in death.[2] The Infectious Disease Society of America recently recommended adding vancomycin to the standard antibiotic coverage (respiratory fluoroquinolones or a beta-lactam plus a macrolide) for patients admitted with CAP severe enough to warrant intensive care unit (ICU) admission.[5] Often times, due to the severity of illness and need for ICU admission, many physicians also prescribe antibiotics to cover Pseudomonas aeruginosa despite the absence of structural lung disease. The objective of the study was to evaluate the prevalence of MRSA and P. aeruginosa and factors associated with failure of therapy.


#

METHODS

Electronic charts of patients with International Classification of Diseases, Ninth Revision (ICD 9) codes of pneumonia who were admitted to the Medical and Surgical ICU at Banner University of Arizona Medical Center (Tucson Campus), a tertiary medical center, from November 2013 through December 2016 were reviewed by the research team. Inclusion criteria included patients who were aged 18 years or older and admitted to the ICU in the first 48 hours of presentation to the hospital with a diagnosis of pneumonia. Patients were excluded if they had risk factors for healthcare-associated pneumonia, including residence in a nursing home or extended care facility, home infusion therapy, chronic dialysis within the last 30 days, home wound care, immunosuppressive disease or therapy, or hospitalization in the last 90 days. Patients who were pregnant, incarcerated, or ventilator dependent were also excluded. The protocol was approved by the University of Arizona Institutional Review Board.

The entire population was used to evaluate factors associated with MRSA pneumonia and poor outcome. Failure was defined as death attributed to pneumonia, patient intubated more than 48 hours after admission to ICU, need for antibiotic escalation, or readmission attributed to pneumonia. “Any failure” was defined as all-cause mortality, patient intubated more than 48 hours after admission to ICU, need for antibiotic escalation, or readmission for any reason. Factors evaluated for association with poor outcome included demographics, signs and symptoms including chest X-ray findings, and medical history (chronic obstructive pulmonary disease [COPD], diabetes, prior antibiotic exposure within 30 days, history of MRSA or pseudomonal infection, or positive MRSA nasal swab within 90 days). The populations of MRSA pneumonia (case and control) were composed of a subset of the entire population. MRSA case subjects had a respiratory culture positive for MRSA during their hospital stay. Subjects included in the MRSA control group had to have a respiratory specimen available that was negative for MRSA and/or a negative MRSA nasal swab. The case and control groups were used to assess potential factors associated with MRSA pneumonia. A similar process was planned for P. aeruginosa pneumonia except the absence of a surrogate marker comparable to the MRSA nasal swab.

Fisher exact test was used to identify factors associated with outcomes or pneumonia type. Classification factors associated with P values <0.2 were further evaluated using multivariate logistic regression. To be retained as a predictive factor, the P value in the final model was needed to be <0.05.

Statistical analysis was performed with SAS version 9.4 (SAS Institute, Cary, NC). Procedure FREQ was used to evaluate differences in proportions with the Fisher option. A t test or Wilcoxon test was used to evaluate differences in age, ICU length of stay, and follow-up times. Logistic regression was performed with factors identified (P < 0.2) by the univariate results. Both forward and backward stepwise procedures were used to ensure model stability.


#

RESULTS

A total of 1065 charts were identified using ICD 9 codes for pneumonia and admission to the ICU. Of these, only 209 patients met appropriate inclusion criteria. The cohort consisted of 104 (49.8%) males and 105 (50.2%) females, predominately white (79.5%) and non-Hispanic (69.7%).

Comorbidities, clinical presentation, microbiology, radiology, and antibiotics prescribed are presented in [Table 1]. The most common comorbidity was COPD (31.1%). Dyspnea was the most common presenting symptoms (83.4%). A total of 117 patients (56%) had a respiratory specimen performed [Table 1], out of which 39 were positive (33.3%). A total of 60 nasal swab MRSA polymerase chain reaction (PCR) tests were performed and only 11 had positive results (18.3%). The most common bacterial cause of pneumonia was Streptococcus pneumoniae. Only seven patients had MRSA (five from sputum and two from tracheal aspirate) and one patient had P. aeruginosa (from tracheal aspirate). Notably only three patients had MRSA bacteremia with no cases of P. aeruginosa bacteremia. A total of 124 cases had negative respiratory specimen and/or MRSA nasal swab (control cases). There were seven cases of MRSA pneumonia. A total of 113 patients (54.1%) received anti-MRSA therapy, 122 (58.4%) received antipseudomonal therapy, and 164 (78.5%) received atypical coverage.

Table 1

Comorbidities, clinical presentation, microbiology, and antibiotic prescription (N = 209)

Parameter

All Subjects

MRSA—case/control populations

(N = 209)

MRSA case (n = 7)

MRSA control (n = 124)

P value

MRSA = methicillin-resistant Staphylococcus aureus, ICU = intensive care unit, COPD = chronic obstructive pulmonary disease, BAL = bronchoalveolar lavage, CXR = chest X-ray, CDI = Clostridium difficile infection, SD = standard deviation, PCR = polymerase chain reaction

Age—mean (SD)

61.5 (17.5)

54.1 (15.1)

6|.5 (|7.5)

>0.2

Sex (female)

104/209 (49.8%)

3/7 (42.9%)

65/|24 (52.4%)

>0.2

Ethnicity (Hispanic)

63/208 (30.3%)

1/7 (|4.3)

39/|24 (3|.5%)

>0.2

Race (white)

163/205 (79.5%)

6/7 (85.7%)

|02/|23 (82.9%)

>0.2

Recent influenza

3/209 (1.44%)

0/7 (0.00%)

2/|24 (|.6|%)

>0.2

Recent antibiotics

26/206 (12.6%)

1/7 (|4.3%)

|7/|23 (|3.8%)

>0.2

Diabetes

29/191 (15.2%)

1/6 (|6.7%)

|7/||6 (|4.7%)

>0.2

COPD

61/196 (31.1%)

2/6 (33.3%)

40/||8 (33.9%)

>0.2

History of MRSA Respiratory specimen

1/209 (0.48 %)

1/7 (|4.3%)

0/|24 (0.00%)

0.0534

BAL

21 (10.1%)

0 (0.00%)

2| (|6.9%)

Sputum

71 (34.0%)

5 (7|.4%)

64 (5|.6%)

>0.2

Trach aspiration

25 (12.0%)

2 (28.6%)

20 (|6.|%)

Not available

92 (44.0%)

0 (0.00%)

|9 (|5.3%)

Positive MRSA nasal swab

11/60 (18.3%)

4/4 (|00%)

0/49 (0.00%)

Positive blood culture

30/202 (14.9%)

3/7 (42.9%)

|8/|23 (|4.6%)

0.083|

Coccidioidomycosis

8/112 (7.14%)

|/6 (|6.7%)

3/69 (4.35%)

>0.2

Positive respiratory PCR panel

13/104 (12.5%)

0/| (0.00%)

|0/72 (|3.9%)

>0.2

Positive influenza PCR

14/117 (12.0%)

0/2 (0.00%)

|2/78 (|5.4%)

>0.2

Cough

133/204 (65.2%)

3/7 (42.9%)

80/|20 (66.7%)

>0.2

Fever

63/203 (31.0%)

5/7 (7|.4%)

39/|22 (32.0)

0.0452

Hypotension

45/200 (22.5%)

3/7 (42.9%)

28/|20 (23.3%)

>0.2

Dyspnea

171/205 (83.4%)

5/7 (7|.4%)

|04/|22 (85.2%)

>0.2

CXR—necrotizing pneumonia

3/209 (1.44%)

|/7 (|4.3%)

|/|24 (0.8|%)

0.|04

CXR—effusion

57/209 (27.3%)

4/7 (57.|%)

30/|24 (24.2%)

0.074|

CXR—multilobular

105/209 (50.2%)

5/7 (7|.4%)

68/|24 (54.8%)

>0.2

Antibiotics > 48 h

197/207 (95.2%)

7/7 (|00%)

||9/|23 (96.8%)

>0.2

Anti-MRSA antibiotic

113/209 (54.1%)

6/7 (85.7%)

70/|24 (56.5%)

>0.2

Antipseudomonal antibiotic

122/209 (58.4%)

6/7 (85.7%)

73/|24 (58.9%)

>0.2

Atypical coverage

164/209 (78.5%)

6/7 (85.7%)

|02/|24 (82.3%)

>0.2

Readmission

63/208 (30.3%)

3/7 (42.9%)

34/|24 (27.4%)

>0.2

Readmission d/t pneumonia

27/205 (13.2%)

2/7 (28.6%)

|7/|23 (|3.8%)

>0.2

CDI within 6 months

8/208 (3.85%)

0/7 (0.00%)

5/|24 (4.03%)

>0.2

Intubation after 48 h

16/207 (7.73%)

0/7 (0.00%)

|2/|24 (9.68%)

>0.2

Antibiotic escalated

17/208 (8.17%)

|/7 (|4.3%)

|2/|24 (9.68%)

>0.2

Death

29/207 (14.0%)

|/7 (|4.3%)

|8/|23 (|4.6%)

>0.2

Death due to pneumonia

20/207 (9.66%)

0/7 (0.00%)

|3/|23 (|0.6%)

>0.2

ICU length of stay (days)

3 (0-50)

7 (3-|5)

3 (2-7)

0.047|

Follow-up duration (days)

180 (|-I80)

|80 (84-|80)

|80 (|7-|80)

>0.2

Independent factors associated with MRSA pneumonia on the univariate analysis (P < 0.2) included history of MRSA (P = 0.053), positive blood culture (P = 0.083), fever (P = 0.045), necrotizing pneumonia (P = 0.104), effusion (P = 0.0741), and ICU length of stay (P = 0.047) [Table 1]. Only effusion (P = 0.001) and fever (P = 0.002) were associated with MRSA pneumonia in the multivariate logistic regression.

A total of 69 patients developed failure (33.0%) and 105 had any failure (50.2%). [Table 2] shows independent variables associated with these primary outcomes. Positive blood culture (P = 0.019), effusion (P = 0.100), receipt of antibiotics over 48 hours (P = 0.080), and receipt of antibiotics against atypical organisms (P = 0.033) were all associated with failure on the univariate analysis. Only positive blood culture (P = 0.010) was associated with failure on the multivariate logistic regression. Similarly, positive blood culture (P = 0.002) was the only independent factor associated with any failure on multivariate logistic regression.

Table 2

Association between dependent variables and primary outcomes (failure and any failure)

Characteristic

Failure present (n = 69)

Failure absent (n = 140)

P value

Any failure present (n = 105)

Any failure absent (n = 104)

P value

MRSA = methicillin-resistant Staphylococcus aureus, COPD = chronic obstructive pulmonary disease, CXR = chest X-ray, PCR = polymerase chain reaction

Sex—female

32/69 (46.4%)

71/140 (51.4%)

>0.2

51/104 (49.0%)

53/140 (50.5%)

>0.2

Ethnicity—Hispanic

18/69 (26.1%)

45/139 (32.4%)

>0.2

28/104 (26.9%)

35/104 (33.7%)

>0.2

Race—white

55/68 (80.9%)

108/137 (78.8%)

>0.2

76/102 (74.5%)

87/103 (84.7%)

>0.2

Recent influenza

2/69 (2.90%)

1/140 (0.71%)

>0.2

2/104 (i.92%)

1/105 (0.95%)

>0.2

Recent antibiotic

61/69 (88.4%)

119/137 (86.9%)

>0.2

13/103 (l2.6%)

13/103 (l2.6%)

>0.2

Diabetes

7/66 (10.6%)

22/125 (17.6%)

>0.2

14/96 (l4.6%)

15/95 (l5.8%)

>0.2

COPD

20/64 (31.3%)

41/132 (31.1%)

>0.2

24/95 (25.3%)

37/101 (36.6%)

0.0920

History of MRSA

1/69 (1.45%)

0/140 (0.0%)

>0.2

1/104 (0.96%)

0/105 (0.0%)

>0.2

Nasal MRSA

3/19 (15.8%)

8/41 (19.5%)

>0.2

6/27 (77.8%)

5/33 (84.9%)

>0.2

Blood culture positive

16/67 (23.9%)

14/135 (66.8%)

0.0193

23/99 (23.2%)

7/103 (6.80%)

0.00l3

Coccidioidomycosis

1/32 (3.13%)

7/80 (8.75%)

>0.2

3/52 (5.77%)

5/60 (8.33%)

>0.2

Positive respiratory PCR

4/38 (10.5%)

9/66 (13.6%)

>0.2

6/53 (ii.3%)

7/51 (l3.7%)

>0.2

Positive influenza PCR

4/40 (10.0%)

10/77 (13.0%)

>0.2

5/55 (9.09%)

9/62 (l4.5%)

>0.2

CXR—necrotizing

1/69 (1.45%)

2/140 (1.43%)

>0.2

2/104 (i.92%)

l/l05 (0.95%)

>0.2

CXR—effusion

24/69 (34.8%)

39/140 (27.9%)

0.0997

36/104 (34.6%)

27/l05 (25.7%)

0.l77

CXR—multilobular

37/69 (53.6%)

72/140 (51.4%)

>0.25

52/104 (50.0%)

57/l05 (54.3%)

>0.2

Cough

42/67 (62.7%)

91/137 (66.4%)

>0.2

62/101 (61.4%)

7l/l03 (68.9%)

>0.2

Fever

22/66 (33.3%)

41/137 (29.9%)

>0.2

29/100 (29.0%)

34/l03 (33.0%)

>0.2

Hypotension

18/66 (27.3%)

27/134 (20.2%)

>0.2

27/99 (27.3%)

l8/l0l (l7.8%)

0.l29

Dyspnea

58/67 (86.6%)

113/138 (67.3%)

>0.2

87/101 (86.1%)

84/l04 (80.8%)

>0.2

Antibiotics > 48 h

61/67 (91.0%)

136/140 (67.3%)

0.0803

94/102 (92.2%)

l03/l05 (98.l%)

0.0562

Anti-MRSA antibiotics

38/69 (55.1%)

75/140 (53.6%)

>0.2

55/104 (47.1%)

47/l05 (44.8%)

>0.2

Antipseudomonal antibiotics

41/69 (59.4%)

65/140 (46.4%)

>0.2

61/104 (58.7%)

6l/l05 (58.l%)

>0.2

Anti-atypical organism

48/69 (69.6%)

81/140 (57.9%)

0.0326

75/104 (72.1%)

89/l05 (84.8%)

0.0294

antibiotics


#

DISCUSSION

In our study, we found that overprescription of antibiotics in the ICU for patients with CAP remains a significant problem. Antipseudomonal coverage and anti-MRSA coverage were often prescribed in this population (58.4% and 54.1%, respectively). Antipseudomonal coverage was rarely necessary as pseudomonal pneumonia was found in only one case (0.9%). This patient did not have history of COPD or bronchiectasis. MRSA was found in only 6.0% of the cases. We found that lack of antipseudomonal and anti-MRSA coverage was not associated with higher rates of primary outcomes (failure or any failure).

Our study does not support the routine use of antipseudomonal and anti-MRSA therapy for patients with CAP in the ICU given low prevalence. It may be necessary to use anti-MRSA therapy in selected patients (e.g., with hypotension, necrotizing pneumonia, and positive nasal swab MRSA PCR).[5],[6] Recent data were published regarding the negative predictive value of a negative nasal swab MRSA PCR. Two studies by Dangerfield et al.[7] and Giancola et al.[6] have shown that a negative nasal swab MRSA PCR indicates the absence of MRSA pneumonia in patients with low MRSA incidence and this test might be used to deescalate antibiotics in cases of negative culture.

Our study has several limitations. It is retrospective in nature and was performed in one center in Southwestern United States, which limits the generalizability of our findings. In addition, only 113 patients (54%) had respiratory culture performed and 90 (43%) had a nasal swab MRSA PCR performed in the previous 90 days. We did not assess timing of antibiotics, which could impact culture and nasal swab data.

Future directions include looking at a larger population subset and further defining populations needing broad-spectrum antibiotics to prevent antibiotic resistance.


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Conflict of Interest

There are no conflicts of interest.

  • References

  • 1 Marrie TJ, Lau CY, Wheeler SL, Wong CJ, Vandervoort MK, Feagan BG. A controlled trial of a critical pathway for treatment of community-acquired pneumonia. CAPITAL study investigators. Community-acquired pneumonia intervention trial assessing levofloxacin. JAMA 2000; 283: 749-55
  • 2 Francis JS, Doherty MC, Lopatin U, Johnston CP, Sinha G, Ross T. et al. Severe community-onset pneumonia in healthy adults caused by methicillin-resistant staphylococcus aureus carrying the panton-valentine leukocidin genes. Clin Infect Dis 2005; 40: 100-7
  • 3 Hageman JC, Uyeki TM, Francis JS, Jernigan DB, Wheeler JD, Bridges CB. et al. Severe community-acquired pneumonia due to staphylococcus aureus, 2003-04 influenza season. Emerg Infect Dis 2006; 12: 894-9
  • 4 Centers for Disease Control and Prevention. Severe methicillin-resistant Staphylococcus aureus community-acquired pneumonia associated with influenza—Louisiana and Georgia, December 2006-January 2007. MMWR Morb Mortal Wkly Rep 2007;56:325-9.
  • 5 Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ. et al. ; Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52: e18-55
  • 6 Giancola SE, Nguyen AT, Le B, Ahmed O, Higgins C, Sizemore JA. et al. Clinical utility of a nasal swab methicillin-resistant Staphylococcus aureus polymerase chain reaction test in intensive and intermediate care unit patients with pneumonia. Diagn Microbiol Infect Dis 2016; 86: 307-10
  • 7 Dangerfield B, Chung A, Webb B, Seville MT. et al. Predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab PCR assay for MRSA pneumonia. Antimicrob Agents Chemother 2014; 58: 859-64

Address for correspondence

Dr. Mayar Al Mohajer
Infection Prevention and Control, Room 508E, Baylor St. Luke’s Medical Center
MC 1–166, 6720 Bertner Ave, Houston, TX 77030
USA   

Publication History

Article published online:
09 August 2021

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  • References

  • 1 Marrie TJ, Lau CY, Wheeler SL, Wong CJ, Vandervoort MK, Feagan BG. A controlled trial of a critical pathway for treatment of community-acquired pneumonia. CAPITAL study investigators. Community-acquired pneumonia intervention trial assessing levofloxacin. JAMA 2000; 283: 749-55
  • 2 Francis JS, Doherty MC, Lopatin U, Johnston CP, Sinha G, Ross T. et al. Severe community-onset pneumonia in healthy adults caused by methicillin-resistant staphylococcus aureus carrying the panton-valentine leukocidin genes. Clin Infect Dis 2005; 40: 100-7
  • 3 Hageman JC, Uyeki TM, Francis JS, Jernigan DB, Wheeler JD, Bridges CB. et al. Severe community-acquired pneumonia due to staphylococcus aureus, 2003-04 influenza season. Emerg Infect Dis 2006; 12: 894-9
  • 4 Centers for Disease Control and Prevention. Severe methicillin-resistant Staphylococcus aureus community-acquired pneumonia associated with influenza—Louisiana and Georgia, December 2006-January 2007. MMWR Morb Mortal Wkly Rep 2007;56:325-9.
  • 5 Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ. et al. ; Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52: e18-55
  • 6 Giancola SE, Nguyen AT, Le B, Ahmed O, Higgins C, Sizemore JA. et al. Clinical utility of a nasal swab methicillin-resistant Staphylococcus aureus polymerase chain reaction test in intensive and intermediate care unit patients with pneumonia. Diagn Microbiol Infect Dis 2016; 86: 307-10
  • 7 Dangerfield B, Chung A, Webb B, Seville MT. et al. Predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab PCR assay for MRSA pneumonia. Antimicrob Agents Chemother 2014; 58: 859-64