|Year : 2016 | Volume
| Issue : 1 | Page : 1-5
Role of clinical pulmonary infection score and serum C-reactive protein in detecting the efficacy of therapeutic choices in the management of Enterobacter aerogenes nosocomial pneumonia
Hany Kmale Mickhael1, Josef Zekry Attia1, Maha Yehia Kamel2
1 Department of Anesthesia and ICU, Faculty of Medicine, Minia University, Minia, Egypt
2 Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt
|Date of Submission||30-May-2015|
|Date of Acceptance||29-Sep-2015|
|Date of Web Publication||15-Jun-2016|
Josef Zekry Attia
Department of Anesthesiology and Intensive Care, Faculty of Medicine, Minia University, 61111 Minia
Source of Support: None, Conflict of Interest: None
Introduction and background Nosocomial pneumonia is the second most common nosocomial infection. It is usually bacterial in origin. Nosocomial pneumonia is responsible for 25% of infections in the ICU. Early-onset nosocomial pneumonia tends to carry a better prognosis than does late-onset nosocomial pneumonia.
Patients and methods This study was planned to evaluate the role of the clinical pulmonary infection score (CPIS) and C-reactive protein (CRP) in detecting the efficacy of antibiotic therapy chosen for treatment of nosocomial Enterobacter pneumonia. In all, 200 patients admitted to the ICU who had evidence of pneumonia were included in the study. Patients were followed up by evaluating their serum CRP levels and CPIS during the first 8 days of admission.
Results Enterobacter aerogenes represented 24% of nosocomial pneumonia cases in the study. An overall 70.8% of patients with E. aerogenes detected in culture and sensitivity were sensitive to both amikacin and levofloxacin. Those patients received only amikacin. Sixteen patients provided good response to amikacin. The remaining 18 patients showed poor response to amikacin therapy (proved by insignificant differences between CPIS and CRP on the first and fourth day of admission). In the case of these patients levofloxacin was added to antibiotic therapy and they were followed up for a further 4 days. The results demonstrated that 16 patients provided good response to amikacin and levofloxacin on the fifth and eighth days.
Conclusion This study demonstrated that CPIS and serum CRP can be used as indicators of the efficacy of antibiotics in nosocomial pneumonia.
Keywords: amikacin, clinical pulmonary infection score, C-reactive protein, Enterobacter aerogenes, levofloxacin
|How to cite this article:|
Mickhael HK, Attia JZ, Kamel MY. Role of clinical pulmonary infection score and serum C-reactive protein in detecting the efficacy of therapeutic choices in the management of Enterobacter aerogenes nosocomial pneumonia. Res Opin Anesth Intensive Care 2016;3:1-5
|How to cite this URL:|
Mickhael HK, Attia JZ, Kamel MY. Role of clinical pulmonary infection score and serum C-reactive protein in detecting the efficacy of therapeutic choices in the management of Enterobacter aerogenes nosocomial pneumonia. Res Opin Anesth Intensive Care [serial online] 2016 [cited 2017 Oct 17];3:1-5. Available from: http://www.roaic.eg.net/text.asp?2016/3/1/1/184075
| Introduction|| |
According to American Thoracic Society (ATS) guidelines, nosocomial pneumonia or hospital-acquired pneumonia is defined as a lung infection that begins in a nonintubated patient within 48 h of admission .
Nosocomial pneumonia is the second most common nosocomial infection and is most prevalent in medical and surgical ICUs. It is usually bacterial in origin. Nosocomial pneumonia is responsible for 25% of infections in the ICU .
The ATS subdivides nosocomial pneumonia into early onset (usually within the first 4 days of hospitalization) and late onset (usually occurring after the fifth hospital day). Early-onset nosocomial pneumonia tends to carry a better prognosis than does late-onset nosocomial pneumonia; the latter tends to be associated with multidrug-resistant organisms and hence is characterized by higher mortality rates ,,. Inhalation, aspiration, and hematogenous spread are the three main mechanisms by which bacteria reach the lungs . The development of nosocomial pneumonia represents an imbalance between normal host defenses and the ability of microorganisms to colonize and then invade the lower respiratory tract . Enterobacter aerogenes is a Gram-negative rod-shaped microorganism from the Enterobacteriaceae family. It is commonly responsible for infections in hospitals; however, it has become a cause for concern in community infections .
| Aim of the Work|| |
This study was planned to evaluate the role of the clinical pulmonary infection score (CPIS) and C-reactive protein (CRP) in the detection of the efficacy of antibiotic therapy chosen for treatment of nosocomial Enterobacter pneumonia.
| Patients and Methods|| |
This study was conducted in the ICU of El-Minia University Hospital from September 2013 to January 2015.
In all, 200 adult patients admitted to the ICU were included in the study:
- All included patients had suspected manifestations of nosocomial pneumonia (considered early-onset pneumonia according to ATS) in the form of:
- Presence of a new or progressive radiographic infiltrate,
- At least two of three of the following features:
- Fever greater than 38°C,
- Leukocytosis or leukopenia,
- Purulent secretions.
- All patients were intubated after establishment of the diagnosis of nosocomial pneumonia and had fulfilled the criteria for intubation and received respiratory support.
- All patients were subjected to the following:
- Hemodynamic monitoring,
- Daily laboratory investigations including total and differential white blood cell count, serum creatinine, liver enzymes, and serum albumin,
- Daily radiological evaluation for new pulmonary infiltrates through plain chest radiographs (posteroanterior view),
- Sputum specimen collection for culture and sensitivity on MacConkey agar,
- Arterial blood gas analysis (pH, PaO2),
- Daily assessment of serum CRP during the first 8 days of intubation,
- Calculation of CPIS , at the onset of suspected pneumonia ([Table 1]).
American Thoracic Society guidelines state that CPIS greater than 6 has a good correlation with the presence of pneumonia .
- Inclusion criteria: According to the results of the culture and sensitivity test, this study included patients with:
- Culture and sensitivity positive for E. aerogenes,
- Sensitivity to the two antibiotics included in this study (amikacin and levofloxacin).
- This study protocol planned to start antibiotic therapy as follows:
- The patients were first given monoantibiotic therapy (amikacin 20 mg/kg daily) and followed up by daily calculation of CPIS and measurement of CRP for 4 days to evaluate improvement.
- Patients who improved on monoantibiotic therapy were considered as group S.
- Patients who did not improve on monoantibiotic therapy (according to CPIS and CRP parameters) were considered as group D. For these patients levofloxacin at 750 mg daily was added to amikacin at 20 mg/kg daily and they were followed up to evaluate their improvement on the basis of CPIS and CRP for the next 4 days.
| Results|| |
This study was carried out in the ICU of El-Minia University Hospital and included 200 patients.
- The number of patients with nosocomial pneumonia caused by E. aerogenes in the study was 48/200 (24%).
- The number of patients with E. aerogenes that was sensitive to the two studied antibiotics (amikacin and levofloxacin) was 34/48 (70.8%).
- These 34 patients who were sensitive to both antibiotics received amikacin only and were followed up on the basis of CPIS and CRP for 4 days.
- Sixteen patients showed clinical improvement and good response to amikacin therapy, as proven by significant decrease in their CPIS and CRP ([Table 2]).
|Table 2: CPIS and CRP in patients with good response to a single antibiotic (group S)|
Click here to view
Response to double antibiotic therapy
The remaining 18 patients (group D) showed no clinical improvement or good response to amikacin therapy, as proven by nonsignificant changes in their CPIS and CRP between the first day of developing pneumonia and the subsequent 4 days ([Table 3]).
|Table 3: CPIS and CRP in patients with poor response to a single antibiotic (group D)|
Click here to view
In group D, levofloxacin was added to antibiotic therapy. Those patients were followed up for a further 4 days, and the results demonstrated that 16 out of 18 patients showed clinical improvement and good response to this double antibiotic therapy, as proven by significant differences in their CPIS and CRP between the fifth and eighth day ([Table 4]). Two patients did not show adequate response and were subjected to further bacteriological study and received other antibiotics; these patients were excluded from the study.
Statistical analysis was performed with Sigma Stat 2.0 (Systat Software Inc., Richmond, California, USA) and SPSS 14 for Windows (SPSS Inc., Chicago, Illinois, USA). The paired t-test was used to compare baseline values and subsequent values of CPIS and CRP.
| Discussion|| |
The international incidence and prevalence of nosocomial pneumonia highlights that nosocomial pneumonia is the most common cause of death among all hospital-acquired infections, with mortality rates of up to 33%. It is common in individuals undergoing mechanical ventilation but can also develop in nonventilated patients. Nosocomial pneumonia has no race or sex predilection. Nosocomial pneumonia is most common in elderly patients; however, patients of any age may be affected .
This study demonstrated that E. aerogenes represents 24% of nosocomial pneumonia cases in the ICU. E. aerogenes forms part of the endogenous human gastrointestinal microflora. It also resides in soil, water, and dairy products. Generally, infections arise from the patient's own flora; however, cross-infection can occur through the hands of healthcare workers, during insertion of medical devices, and during surgical procedures. Contaminated surfaces may play a role in the transmission of Enterobacter spp., particularly during outbreaks . Most cases of Enterobacter bacteremia are nosocomial, and frequently acquired in the ICU. The portal of entry into the bloodstream is frequently unknown, but any infected organ, central line, or arterial catheters may be the primary source of bacteremia . The primary route through which organisms enter the lower airways is through aspiration of oropharyngeal secretions into the trachea. Primary inhalation pneumonia develops when these organisms bypass normal respiratory defense mechanisms or when the patient inhales aerobic Gram-negative organisms that colonize the upper respiratory tract or respiratory support equipment. Aspiration pneumonia is due to the aspiration of colonized upper respiratory tract secretions . The stomach appears to be an important reservoir of Gram-negative bacilli that can ascend and colonize the respiratory tract. A prospective observational study found that patients who used acid-suppressive medications were more likely to develop hospital-acquired pneumonia than were patients who did not (5 vs. 2%). Further evaluation by drug class showed that the risk for pneumonia was significantly increased with proton pump inhibitors, but not with histamine 2-blocking agents .
This study showed that 70.8% of patients with E. aerogenes detected in culture and sensitivity were sensitive to both amikacin and levofloxacin, and 16 out of 34 patients provided good response to amikacin therapy as indicated by CPIS and CRP.
Nosocomial pneumonia adds significantly to the cost of hospital care and to the length of hospital stay and accounts for the use of 50% of all antibiotics administered in the hospital. Therefore, early diagnosis and early determination of the most effective antibiotic may decrease the time of hospital admission and decrease usage of antibiotics . Although most patients with nosocomial pneumonia develop fever and leukocytosis, these findings are not uniform and are not a requisite for the presumptive diagnosis of nosocomial pneumonia . Respiratory tract symptoms include an increase in respiratory rate, shortness of breath, and productive cough . Although it is supported by appropriate cultures, these can include semiquantitative cultures from bronchoalveolar lavage samples. The definitive diagnosis of nosocomial pneumonia rests on tissue biopsy, which is rarely performed. Therefore, the clinician must factor in various findings that are not specific to nosocomial pneumonia . The most commonly used criteria are the presence of three of the following: fever, elevated white blood cell count, infected appearing sputum, or worsening oxygenation. Although specifically based on cases of ventilator-associated pneumonia, these criteria also appear to be valid for hospital-acquired pneumonia and healthcare-associated pneumonia. This diagnostic approach is 69% sensitive and 75% specific .
American Thoracic Society guidelines mentioned that CPIS greater than 6 shows a good correlation with the presence of pneumonia .
Pugin et al.  evaluated 79 episodes of suspected ventilator acquired pneumonia (VAP) using the CPIS and compared the findings with diagnosis established by bronchoalveolar lavage culture. A persistently low score less than 6 for 3 days in patients with suspected nosocomial pneumonia makes the diagnosis unlikely and might guide the decision to stop treatment with antibiotics .
Singh et al.  used a modified CPIS that did not rely on culture data to guide clinical management of nosocomial pneumonia . They have shown that some patients with a low clinical suspicion of VAP (CPIS of 6 or less) can have antibiotics safely discontinued after 3 days, if the subsequent course suggests that the probability of pneumonia is still low. This modified CPIS used by Singh et al.  appears to be an objective measure to define patients who can receive a short duration of therapy.
Luna et al.  suggested that re-evaluation of the decision to use antibiotics based on serial clinical evaluations, by the third day or sooner, is necessary because patients who are improving will have signs of good clinical response by this time .
In this study, 18 patients did not provide good response to amikacin therapy and hence levofloxacin was added to antibiotic therapy. These patients were followed up for a further 4 days. The results demonstrated that 16 patients showed good response to this combination, as proved by significant difference between CPIS and CRP on the fifth and eighth days.
Enterobacter spp. are notorious for their drug resistance, which is thought to have been amplified by the use of broad-spectrum cephalosporins in hospitals .
E. aerogenes uses three mechanisms of resistance: inactivating enzymes, alteration of drug targets, and alteration of the ability of drugs to enter and or accumulate in cells .
The susceptibility of Enterobacter spp. strains varies widely, but 'older' antibiotics such as colistin may be required to treat multidrug resistance. Some of the antibiotics that E. aerogenes is known to be resistant to include β-lactam antibiotics, aminoglycosides, and quinolones .
| Conclusion|| |
This study demonstrated that CPIS and serum CRP can be used as indicators of efficacy of antibiotics in nosocomial pneumonia.
| Acknowledgements|| |
The authors thank all members of the Anesthesia and ICU Department, Faculty of Medicine, Minia University.
Conflicts of interest
There are no conflicts of interest.
| References|| |
American Thoracic SocietyInfectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 15:388–416.
Cunha BA. Multi-drug resistant (MDR) Klebsiella
, and Pseudomonas aeruginosa
. Antibiot Clin 2006;10:354–355.
Furtado GH, d'Azevedo PA, Santos AF, et al.
Intravenous polymyxin B for the treatment of nosocomial pneumonia caused by multidrug-resistant Pseudomonas aeruginosa
. Int J Antimicrob Agents 2007; 30:315–319.
Mesaros N, Nordmann P, Plesiat P, et al. Pseudomonas aeruginosa
: resistance and therapeutic options at the turn of the new millennium. Clin Microbiol Infect 2007; 13:560–578.
Wang S, Kwok M, McNamara JK, Cunha BA. Colistin for multi-drug resistant (MDR) Gram-negative bacillary infections. Antibiot Clin 2007; 11:389–396.
Ferrara AM. Potentially multidrug-resistant non-fermentative Gram-negative pathogens causing nosocomial pneumonia. Int J Antimicrob Agents 2006; 27:183–195.
Agodi A, Barchitta M, Cipresso R, et al. Pseudomonas aeruginosa
carriage, colonization, and infection in ICU patients. Intensive Care Med 2007; 33:1155–1161.
Sanders WE, Sanders CC. Enterobacter
spp.: pathogens poised to flourish at the turn of the century. Clin Microbiol Rev 1997; 10:220–241.
Pugin J, Auckenthaler R, Mili. N, et al.
Diagnosis of ventilator – associated pneumonia by bacteriologic analysis of bronchoscopic and non-bronchoscopic 'blind' bronchoalveolar lavage fluid. Am Rev Respir Dis 1991; 149:1121–1129.
Fartoukih M, Maitre B, Honore S, et al.
Diagnosing pneumonia during mechanical ventilation: the clinical pulmonary infection score revisited. Am J Respir Crit Care Med 2003; 168:173–179.
Otter J, Yezli S, Schouten M, van Zanten A, Houmes-Zielman G, Nohlmans-Paulssen M. Hydrogen peroxide vapor decontamination of an intensive care unit to remove environmental reservoirs of multidrug-resistant gram-negative rods during an outbreak. Am J Infect Control 2010; 38:754–756.
Rossi F, Baquero F, Hsueh PR, et al. In vitro
susceptibilities of aerobic and facultatively anaerobic Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). J Antimicrob Chemother 2006; 58:205–210.
Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA 2009; 301:2120–2128.
Fàbregas N, Ewig S, Torres A, El-Ebiary M, Ramirez J, de La Bellacasa JP, et al.
Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies. Thorax 1999; 54:867–873.
Singh N, Rogers P, Atwood C, et al.
Short course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit: a proposed solution for in discriminate antibiotic prescription. Am J Respir Crit Care Med 2000; 162:505–511.
Luna C, Blanzaco D, Niederman M, et al.
Resolution of ventilator – associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome. Crit Care Med 2003; 31:676–682.
Giamarellou H. Multidrug resistance in Gram-negative bacteria that produce extended-spectrum beta-lactamases (ESBLs). Clin Microbiol Infect 2005; 11:1–16.
[Table 1], [Table 2], [Table 3], [Table 4]