Open Access

Are third-generation cephalosporins unavoidable for empirical therapy of community-acquired pneumonia in adult patients who require ICU admission? A retrospective study

  • Geoffroy Hariri1,
  • Jacques Tankovic2,
  • Pierre-Yves Boëlle3, 4,
  • Vincent Dubée1, 4,
  • Guillaume Leblanc1,
  • Claire Pichereau1,
  • Simon Bourcier1,
  • Naike Bigé1,
  • Jean-Luc Baudel1,
  • Arnaud Galbois1, 5,
  • Hafid Ait-Oufella1, 4 and
  • Eric Maury1, 3, 4Email author
Annals of Intensive Care20177:35

https://doi.org/10.1186/s13613-017-0259-4

Received: 6 October 2016

Accepted: 15 March 2017

Published: 24 March 2017

Abstract

Background

Third-generation cephalosporins (3GCs) are recommended for empirical antibiotic therapy of community-acquired pneumonia (CAP) in patients requiring ICU admission. However, their extensive use could promote the emergence of extended-spectrum beta-lactamases-producing Enterobacteriaceae. Our aim was to assess whether the use of 3GCs in patients with CAP requiring ICU admission was justified.

Methods

We assessed all patients with CAP who required ICU admission during a 7-year period. We recorded empirical and definitive antibiotic therapies and susceptibility of causative pathogens. Amoxicillin, amoxicillin/clavulanate (A/C) susceptibilities as well as amikacin susceptibility of A/C-resistant strains were recorded.

Results

From January 2007 to March 2014, 391 patients were included in the study. Empirical 3GCs were used in 215 patients (55%). Among 267 patients with microbiologically documented CAP (68%), 241 received a beta-lactam as definitive therapy, and of those, 3CGs were chosen for 43 patients (18%). Amoxicillin or A/C was active against isolated pathogens in 159 patients (66%), while 39 patients (16%) required a beta-lactam with a broader spectrum than 3GCs. Ninety-four per cent of A/C-resistant strains were amikacin susceptible.

Conclusions

In ICU patients with CAP, 3GCs given on an empirical basis are changed, according to microbiological documentation, for another beta-lactam in 82% of cases especially to A/C in the absence of resistance risk factor. In patients evidencing risk factors for A/C-resistant strains infection, 3GCs or antipseudomonal beta-lactams including carbapenem associated with amikacin in the most severe patients seem a relevant empirical antibiotic therapy. This strategy could decrease 3GCs’ use.

Keywords

Community-acquired pneumonia Third-generation cephalosporins Extended-spectrum beta-lactamases Intensive care unit Antibiotics

Background

Community-acquired pneumonia (CAP) is a major cause of hospitalization and death worldwide [1, 2]. CAP is the leading infectious cause for admission in the intensive care unit (ICU) and one of the most common causes of sepsis, severe sepsis and septic shock [3, 4]. Guidelines published in 2006 by the French Intensive Care Society (SRLF) and the French Infectious Diseases Society (SPILF) [5] recommended a non-antipseudomonal third-generation cephalosporin (3GC, as ceftriaxone or cefotaxime) in combination with either a macrolide or a fluoroquinolone for empirical treatment of patients with severe CAP who require ICU admission. Since the publication of those recommendations, a sharp increase in 3GCs prescription has been observed, with a 58% increase in ceftriaxone use in France between 2008 and 2013 (French National Institute for Public Health Surveillance, RAISIN) [6]. Between 2003 and 2012, the incidence of third-generation cephalosporin-resistant strains, especially extended-spectrum beta-lactamases-producing Enterobacteriaceae (ESBLEs), increased from 0.17 to 0.48 per 1000 hospitalization days [7].

Furthermore, the increased incidence of ESBLEs promotes the use of carbapenems, which in turn could increase the risk of emergence and spreading of carbapenem-resistant strains. A restricted use of 3GCs could therefore be warranted [9], as it might provide a possible strategy to decrease incidence of 3GCs’ resistance [10]. Thus, the aim of our study was to assess whether the use of 3GCs in patients with CAP who require ICU admission was justified based on the microbiologically identified causative pathogen and its susceptibility pattern.

Methods

The study was conducted in a 670-bed tertiary teaching hospital in Paris, France. We retrospectively reviewed medical records of all consecutive adult patients who required ICU admission between January 2007 and March 2014 for acute respiratory failure. Pneumonia was diagnosed with the following criteria: a new alveolar, interstitial or alveolo-interstitial opacity on chest radiography, associated with at least two of the following: cough, sputum production, temperature above 38 °C or below 35 °C, and auscultatory findings consistent with pneumonia or dyspnoea. To be considered a community-acquired pneumonia, symptoms had to develop in the community or within the first 48 h after hospital admission [1113]. Patients were admitted to the ICU from the emergency department or directly from the pre-hospital emergency medical team. The institutional review board of our institution approved the study.

For each patient included in the study, the following parameters were recorded: age, sex, underlying comorbidities (chronic lung disease, hypertension, diabetes, chronic liver disease, heart failure, chronic renal disease, HIV infection, ongoing solid cancer or blood cancer), SAPS II score, mechanical ventilation use, intravenous vasopressors administered for septic shock and ICU mortality.

A pathogen was considered causal for CAP after a comprehensive and critical appraisal of clinical and microbiological data. The microbiological diagnostic workup for all patients included: blood cultures obtained upon admission and before antibiotic administration, expectorated sputum sample in patients able to cough or blind endotracheal aspirations in patients mechanically ventilated. A broncho-alveolar lavage through fibroscopy was performed if others means were deemed unsuccessful. Respiratory samples were analysed for Gram staining initially and after 48 h of culture. According to international guidelines, immunochromatographic tests for detection of Streptococcus pneumoniae and Legionella pneumophila serogroup 1 antigen in urine were also performed [5]. The addition of PCR virus detection on lower respiratory samples or nasal–pharyngeal swabs (e.g. specific influenza PCR testing during the flu-season or respiratory virus PCR panel), or direct detection and quantitative PCR assessment of Pneumocystis jirovecii on broncho-alveolar fluid in patients with underlying immunosuppression was left at the discretion of the attending intensivist.

As per French guidelines, at our institution the combination of ceftriaxone or cefotaxime with either a macrolide or a fluoroquinolone is used as empirical treatment of patients with severe CAP requiring ICU admission. Then, as suggested by internal protocols, empiric antimicrobial therapy would be reassessed after 48 h by attending physicians and adjusted according to the microbiological cultures, if available. The most narrow-spectrum antibiotic would be used as the definitive therapy based on antimicrobial susceptibility results based on the antibiogram diameter inhibition and switched to the oral route as soon as possible. If pneumococcal pneumonia were documented, the association of a beta-lactam and a macrolide would be maintained for the first 3 days [14] and then a beta-lactam (usually amoxicillin) would be maintained alone thereafter. If all cultures would remain negative in a patient having received any antibiotic before microbiological samples, the empiric therapy would be switched to oral pristinamycin. However, special attention would be paid to the direct examination of the sputum specimen in those patients, as the presence of typical Gram stain aspects (e.g. Gram-positive diplococci or numerous Gram-negative bacilli) might modify the choice of definitive therapy. In general, fluoroquinolones use was discouraged except in case of confirmed severe legionellosis [15].

The appropriateness of the 3GCs utilization was assessed in patients with microbiologically documented pneumonia, based on the susceptibility of the identified pathogens. Since Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines recommend 3GC or combination of amoxicillin/β-lactamase inhibitor in case of severe CAP [11], special attention was paid to amoxicillin/clavulanate (A/C) susceptibility. The empirical use of 3GCs was therefore classified as:
  • Unjustified when the pathogen was susceptible to amoxicillin or amoxicillin/clavulanate (A/C);

  • Appropriate when the pathogen was resistant to amoxicillin/clavulanic acid and susceptible to non-antipseudomonal 3GCs;

  • Insufficient when the pathogen was resistant to both amoxicillin/clavulanate and non-antipseudomonal 3GCs and required a broader-spectrum beta-lactam.

In patients presenting with CAP exhibiting A/C-resistant strains, we revised the charts to explore the presence of underlying comorbidities previously reported as risk factors for resistant pathogens [16] (e.g. chronic lung disease, hypertension, diabetes, chronic liver disease, heart failure, renal failure, HIV infection, stroke, ambulatory status, previous antibiotic treatment and progressive cancer). In those patients, we assessed the susceptibility to aminoglycosides (amikacin and gentamicin).

Statistical analysis

Data are presented as numbers and percentages for categorical variables and mean ± standard deviation (SD) for continuous variables. Comparison between groups was made using Pearson’s Chi-squared test. P values <0.05 indicated statistical significance. Odds ratios for risk factors for A/C resistance were determined by logistic regression. An univariable analysis was first performed, and variables showing association with A/C resistance (P < 0.15) were included in a multivariate analysis, to calculate odds ratios. All analyses were performed using R 2.11.1 statistical package.

Results

Between January 2007 and March 2014, 7676 patients were admitted in the ICU. Out of 1071 patients hospitalized in the ICU for acute respiratory failure, a final diagnosis of CAP was made in 391 patients (Fig. 1).
Fig. 1

Flow chart of patients included in the analysis. HAP hospital-associated pneumonia, ARF acute respiratory failure, COPD chronic obstructive pulmonary disease

Of these 391 patients (55% male, mean age: 65 ± 19 years, SAPS II score of 47 ± 22), 172 (44%) required mechanical ventilation and 107 (27%) received vasopressors. Overall mortality during the ICU stay was 18% (73 patients). Patients’ characteristics are presented in Table 1.
Table 1

Patients’ characteristics

Characteristics

N

%

Sex (male)

215

55.0

Age

65 ± 19

 

IGSII

47 ± 22

 

Chronic lung disease

119

30.4

HTA

142

36.3

Diabetes mellitus

57

14.6

Congestive heart failure

43

11.0

Chronic liver disease

41

10.4

Chronic renal disease

23

5.9

Stroke

19

4.9

Progressive cancer

22

5.6

Blood cancer

37

9.5

HIV

20

5.1

Other causes of immunosuppression

8

2.0

Mechanical ventilation

172

44.0

Catecholamines

107

27.3

Acute renal failure

16

4.1

Renal replacement therapy

1

0.3

Mortality

73

18.6

The initial empiric antibiotic therapy consisted in a monotherapy in 53 patients (13%), a bitherapy in 312 patients (80%) and a tritherapy in 21 patients (5%). The bitherapies consisted in beta-lactam and macrolide (n = 277), beta-lactam and metronidazole (n = 34) and sulphonamides and macrolide (n = 1). The beta-lactams more frequently used were: a non-antipseudomonal 3GC in 215 patients (55%) and amoxicillin/clavulanate in 75 patients (19%) (Table 2). Macrolides were empirically prescribed in 277 patients (70%). Oseltamivir was associated with antibiotic therapy on an empirical basis in 23 patients.
Table 2

Anti-infective therapies administered on an empirical basis to the 391 patients with community-acquired pneumonia

Empirical antibiotic therapies

N (%)

Macrolides

277 (71)

Third-generation cephalosporin

215 (55)

Amoxicillin/clavulanate

75 (19)

Piperacillin/tazobactam

64 (16)

Metronidazole

34 (12)

Oseltamivir

23 (6)

Cotrimoxazole

18 (5)

Fluoroquinolone

15 (4)

Aminoglycoside

9 (2)

Imipenem

9 (2)

Amoxicillin

7 (2)

Vancomycin

6 (2)

Ceftazidime

3 (1)

Microbiologically proven community-acquired pneumonia

A causative pathogen was identified in 267 patients (68%) (Table 3). Streptococcus pneumoniae and Haemophilus influenzae were the most frequent pathogens, identified in 43.1 and 17.6% of cases, respectively.
Table 3

Distribution of pathogens identified in 267 patients with documented community-acquired pneumonia

Microbiological strains

n (%)

Streptococcus pneumonia

115 (43.1)

Haemophilus influenza

47 (17.6)

Moraxella catarrhalis

4 (1.5)

Legionella pneumophila

7 (2.6)

Mycoplasma pneumoniae

1 (0.3)

Enterobacteriaceae

 

 Escherichia coli

22 (8.2)

 Klebsiella pneumoniae

15 (5.6)

 Klebsiella oxytoca

3 (1.1)

 Serratia marcescens

4 (1.5)

 Enterobacter cloacae

4 (1.5)

 Morganella morganii

3 (1.1)

 Proteus mirabilis

2 (0.7)

 Hafnia alvei

1 (0.3)

 Enterobacter aerogenes

1 (0.3)

Non-fermenting Gram-negative bacteria

 Pseudomonas aeruginosa

22 (8.2)

 Stenotrophomonas maltophilia

2 (0.7)

 Acinetobacter baumannii

1 (0.3)

Methi-S Staphylococcus aureus

18 (5.7)

Methi-R Staphyloccocus aureus

3 (1.1)

Corynebacterium

3 (1.1)

Fusobacterium other

1 (0.3)

Neisseiria sp. other

1 (0.3)

Streptococcus anginosus other

1 (0.3)

Streptococcus milleri other

2 (0.3)

Pneumocystis jirovecii

11 (4.1)

Viruses

 

 H1N1 influenzae

4 (1.5)

 Adenovirus

1 (0.3)

Mycobacterium tuberculosis

1 (0.3)

The total count of pathogens exceeds the total number of documented pneumonia since 33 pneumonias were caused by two pathogens

Among the 267 patients with microbiologically proven CAP, 241 were given a beta-lactam alone as a definitive therapy (Table 4). In these patients, the empirical prescription of 3GCs was unjustified in 159 patients (66%) and was changed for amoxicillin/clavulanate (n = 70), amoxicillin (n = 87) or oxacillin (n = 2). The empirical 3GC’s prescription was appropriate and continued in 43 patients (18%) and insufficient in 39 patients (16%) in whom a broader-spectrum beta-lactam was required for definitive therapy. Finally, in patients with documented pneumonia requiring beta-lactam, non-antipseudomonal 3GCs prescribed on an empirical basis were justified in less than a fifth of patients (Fig. 2).
Table 4

Empiric and definitive beta-lactams given to 241 patients with documented pneumonia requiring at least a beta-lactam

Beta-lactam

n (%)

Non-antipseudomonal 3GC unjustified

159 (65.9)

 Amoxicillin

87 (36.1)

 Amoxicillin/clavulanate

70 (29)

 Oxacillin

2 (0.8)

Non-antipseudomonal 3GC appropriate

43 (17.8)

Non-antipseudomonal 3GC inappropriate

39 (16.2)

 Piperacillin/tazobactam

16 (6.7)

 Ticarcillin

9 (3.7)

 Carbapenem

7 (2.9)

 Ceftazidime

3 (1.2)

 Tazocillin/clavulanate

2 (0.8)

 Cefepime

1 (0.4)

 Piperacillin

1 (0.4)

Fig. 2

Relevance of third-generation cephalosporins given on an empirical basis to patients with documented community-acquired pneumonia and requiring at least a beta-lactam

No pneumococcal strain exhibited resistance to amoxicillin. Among H influenza strains, 43% were fully amoxicillin susceptible and 36% were amoxicillin resistant and A/C susceptible, whereas 21% were A/C resistant and cefotaxime susceptible. All Haemophilus strains were susceptible to spiramycin. Resistance to cefotaxime was mainly observed in non-fermenting Gram-negative bacilli. All patients with Pseudomonas aeruginosa-associated CAP had at least one of the specific risk factor previously defined in French guidelines [17].

Resistance to amoxicillin/clavulanate was observed in 82 patients and was more frequent among patients with comorbidities (Table 5). In the multivariable analysis, variables significantly associated with resistance to amoxicillin/clavulanate were chronic lung disease [OR 1.9 (95% CI 1–3.6)], cancer [OR 4.5 (95% CI 2.0–9.8)], previous antibiotic therapy [OR 2.7 (95% CI 1.3–5.9)], limited autonomy [OR 2.9 (95% CI 1.0–8.2) and stroke [OR 0.1 (95% CI 0.0–0.9)].
Table 5

Univariable and multivariable analysis of comorbidities associated with infection due to amoxicillin/clavulanate non-susceptible

Comorbidities

Univariable analysis

Multivariable analysis

OR (95% CI)

P value

OR (CI 95%)

P value

Arterial hypertension

1.3 (0.7–2.2)

0.40

  

Chronic lung disease

1.7 (0.9–3.1)

0.09

1.9 (1.0–3.6)

0.05

Chronic renal failure

1.6 (0.4–6.0)

0.52

  

Chronic liver disease

0.7 (0.3–1.6)

0.36

  

Congestive heart failure

1.2 (0.4–3.3)

0.78

  

Immunosuppression (HIV, other)

2.0 (0.8–5.1)

0.13

  

Diabetes mellitus

1.0 (0.4–2.4)

0.97

  

Cancer

4.3 (2.1–9.1)

0.001

4.5 (2.0–9.8)

0.04

Stroke

0.2 (0.0–1.2)

0.07

0.1 (0.0–0.9)

0.03

Nursing home/non-ambulatoryb

2.1 (0.9–5.0)

0.11

2.9 (1.0–8.2)

0.04

Proton pump inhibitor

1.1 (0.5–2.1)

0.85

  

Other immunosuppression

2.4 (0.7–8.1)

0.16

  

Hospitalizationa

1.6 (0.8–3.4)

0.23

  

Antibiotic during last 90 days

2.7 (1.3–5.6)

0.01

2.7 (1.3–5.9)

0.01

aAt least 2 days in the last 90 days

bNon-ambulatory status was defined as being bedridden or using a wheelchair because of difficulty walking

Among the 82 pathogens resistant to amoxicillin/clavulanate, 18 strains (22%) were resistant to gentamicin, whereas five strains (6%) were resistant to both gentamicin and amikacin.

Discussion

In our retrospective study, we evaluated the efficacy and relevance of the chosen empirical antibiotic therapy especially non-antipseudomonal 3GCs in the light of the microbiologically identified pathogens and their susceptibility result. To assess whether 3GCs were really justified, we focused on CAP with microbiological documentation, which required definitive beta-lactam therapy. These infections were separated into three groups according to whether 3GCs appeared unjustified (pathogen susceptible either to amoxicillin or amoxicillin/clavulanate), appropriate (pathogen cefotaxime susceptible and resistant to amoxicillin/clavulanate) or insufficient (pathogen resistant to both amoxicillin/clavulanate and non-antipseudomonal 3GCs and requiring a broader-spectrum beta-lactam).

In the present study, 3GCs were the second most frequent empirical antibiotic used for severe CAP after macrolides (53 and 70%, respectively). This is in agreement with French guidelines [5]. Streptococcus pneumoniae and Haemophilus influenzae remain, as previously observed [1822], the most frequent bacterial species causing CAP. These two pathogens accounted for 60% cases of documented pneumonias. These pathogens are most often highly susceptible to narrow-spectrum β-lactams such as amoxicillin or amoxicillin/clavulanate [20], except for some H. influenzae isolates. In the present studies, 10 H influenzae strains (21%) were amoxicillin/clavulanate resistant, but all were susceptible to both cefotaxime and spiramycin.

The group of unjustified third-generation cephalosporin prescription is the most important with 66% (159) of patients with documented infection; in this group, treatment with amoxicillin or amoxicillin/clavulanate would have been sufficient. Appropriate 3GC’s prescription was observed in only 18% (43 patients) of our cohort. Finally, the group in which third-generation cephalosporin use appeared insufficient represents 16% (39) of patients, meaning that in these patients a beta-lactam with a broader spectrum than 3GCs would have been required.

These results suggest that the use of third-generation cephalosporins as an empiric beta-lactam for treatment of severe community-acquired pneumonia admitted to the ICU is a perfectly tailored antibiotic therapy in only one out of five patients. Most of the time, a narrower-spectrum beta-lactam might be preferred. The amoxicillin/clavulanate combination would be a satisfactory alternative to 3GCs against two-thirds of overall recovered pathogens. Moreover, non-antipseudomonal 3GC spectrum appears insufficient in one out of six patients with CAP requiring beta-lactam.

In a second part of the study, we sought to delineate patients for whom amoxicillin/beta-lactamase inhibitor would be insufficient and who would require a broader-spectrum beta-lactam. For that, we assessed the presence or absence of risk factors associated with colonization/infection with resistant strains previously reported [21]. We found that chronic lung disease, ongoing cancer, non-ambulatory status and previous antibiotic therapy were significantly associated with amoxicillin/clavulanate-resistant strains.

These amoxicillin/clavulanate-resistant isolates (mainly Pseudomonas aeruginosa, non-fermenting Gram-negative bacilli and several Enterobacteriaceae) were most of the time sensitive to amikacin (94%), suggesting that this antibiotic could be considered in patients with risk factors for infection with an amoxicillin/clavulanate non-susceptible pathogen.

Prior use of 3CGs has been identified as a risk factor for infections caused by ESBL-producing Enterobacteriaceae [8, 23, 24]. Recent experiments report a decrease in ESBLEs emergence following decrease in cephalosporins use [10]. These data support, when possible, a decrease in the use of 3CGs to control ESBL-producing Enterobacteriaceae spreading. According to our results, amoxicillin/clavulanate could be proposed as an alternative beta-lactam for severe CAP in patients without risk factors for amoxicillin/clavulanate resistance. This situation (absence of A/C resistance risk factor) is observed in 55% of patients.

Such a strategy could contribute to limit the 3GCs use and then probably the emergence of extended-spectrum beta-lactamases (ESBLs). It is important to note that conversely to French recommendations, amoxicillin/beta-lactamase inhibitor is proposed as a possible first-line empirical beta-lactam for ICU patients with CAP in North American [11] and British [25] guidelines. Reducing the use of third-generation cephalosporins for CAP is already suggested in the emergency department [26].

Among patients with risk factors for amoxicillin/clavulanate resistance, strains encountered are very similar to those observed in patients with healthcare-associated pneumonia, and even this is still debated, to strains identified in patients with ventilator-associated pneumonia and/or hospital-acquired pneumonia [1627]. The latter patients should receive at least 3GCs for empirical treatment and antipseudomonal beta-lactam (piperacillin/tazobactam, cefepime, ceftazidime) or carbapenem associated with an aminoglycoside for the most severe patients. Amikacin appears in the present study more frequently efficient than gentamicin.

The present study has, however, several limitations. First, whereas some of the observed data are similar to previously published results, the present study is a single-centre retrospective study with a moderate size population. Thus, these results should be interpreted cautiously and confirmed in a larger population. Second, our approach relies on an extensive infectious workup including invasive procedures, which is a strategy not supported by current guidelines in non-immunocompromised patients. Nevertheless, owing to significant increase in antibiotic resistance and to the necessity of a relevant antimicrobial stewardship, an aggressive diagnostic approach dedicated to increase the rate of microbiological identification in order to use the antibiotic therapy with the narrowest spectrum seems mandatory.

Conclusion

In ICU patients with documented community-acquired pneumonia who require definitively a beta-lactam, we observed that 3GCs are most of the time an unjustified or insufficient antibiotic therapy. Based on the present retrospective analysis, a narrower-spectrum beta-lactam antibiotic with amoxicillin/clavulanate combined with a macrolide could replace 3GCs as empirical antibiotics for severe CAP in patients without risk factors for amoxicillin/clavulanate resistance, i.e. chronic lung disease, ongoing cancer, non-ambulatory status and antibiotic therapy during the previous 90 days. In patients with risk factors for amoxicillin/clavulanate resistance, 3GCs, antipseudomonal beta-lactam including carbapenem associated with amikacin in the most severe patients seems a relevant empirical antibiotic therapy. This strategy could promote a decrease in 3GCs’ consumption.

Abbreviations

3GC: 

third-generation cephalosporin

ESBL: 

extended-spectrum beta-lactamase

ICU: 

intensive care unit

CAP: 

community-acquired pneumonia

HCAP: 

healthcare-associated pneumonia

A/C: 

amoxicillin/clavulanate

Declarations

Authors’ contributions

GH took part to the conception and design of the study, acquired the data, had major input in the data analysis and wrote the draft of the manuscript. JT took part to the design of the study and extracted the microbiological data. PYB took part to the design of the study and conducted uni- and multivariable analysis and had major input in the data analysis. VD contributed to data analysis, and GL contributed to database elaboration. CP, SB, NB, JLB, AG and HAO took part to the design of the study and contributed to data analysis. EM conceptualized and designed the study, contributed to database elaboration, had major input in data interpretation and had major input in manuscript writing and revision. All authors read and approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

Availability of data and materials

Medical files can be found in our ICU 4D fusion software database. Microbiological data can be found in the data base of our hospital microbiology department.

Ethical approval and consent to participate

The institutional review board of our hospital authorized this retrospective analysis. All patients or next of kin gave their consent for the data obtained during their ICU stay to be retrospectively analysed.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors’ Affiliations

(1)
Service de Réanimation Médicale, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris
(2)
Microbiologie, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris
(3)
Institut Pierre-Louis d’Epidémiologie et de Santé Publique, U 1136, Inserm
(4)
UPMC Univ Paris 06, Sorbonne Universités
(5)
Réanimation Polyvalente, HP Claude Galien

References

  1. Torres A, Peetermans WE, Viegi G, Blasi F. Risk factors for community-acquired pneumonia in adults in Europe: a literature review. Thorax. 2013;68:1057–65.View ArticlePubMedPubMed CentralGoogle Scholar
  2. Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med. 2014;371:1619–28.View ArticlePubMedGoogle Scholar
  3. Walden AP, Clarke GM, McKechnie S, Hutton P, Gordon AC, Rello J, et al. Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort. Crit Care. 2014;18:R58. doi:10.1186/cc13812.View ArticlePubMedPubMed CentralGoogle Scholar
  4. Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007;167:1655–63.View ArticlePubMedPubMed CentralGoogle Scholar
  5. Société de Réanimation de Langue Française. 15th consensus conference about management of lower respiratory tract infections in immunocompetent adult. Med Mal Infect. 2006;36:235–44.View ArticleGoogle Scholar
  6. Desenclos JC, RAISIN Working Group. RAISIN—a national programme for early warning, investigation and surveillance of healthcare-associated infection in France. Euro Surveill. 2009;14:1–8.Google Scholar
  7. Carbonne A, Arnaud I, Maugat S, Marty N, Dumartin C, Bertrand X, et al. National multidrug-resistant bacteria (MDRB) surveillance in France through the RAISIN network: a 9 year experience. J Antimicrob Chemother. 2013;68:954–9.View ArticlePubMedGoogle Scholar
  8. Gbaguidi-Haore H, Dumartin C, L’Hériteau F, Péfau M, Hocquet D, Roques AM, et al. Antibiotics involved in the occurrence of antibiotic-resistant bacteria: a nationwide multilevel study suggests differences within antibiotic classes. J Antimicrob Chemother. 2013;68:461–70.View ArticlePubMedGoogle Scholar
  9. Carlet J. Ten tips on how to win the war against resistance to antibiotics. Intensive Care Med. 2015;41:899–901.View ArticlePubMedGoogle Scholar
  10. Livermore DM, Hope R, Reynolds R, Blackburn R, Johnson AP, Woodford N, et al. Declining cephalosporin and fluoroquinolone non-susceptibility among bloodstream Enterobacteriaceae from the UK: links to prescribing change? J Antimicrob Chemother. 2013;68:2667–74.View ArticlePubMedGoogle Scholar
  11. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:27–72.View ArticleGoogle Scholar
  12. Johnstone J, Majumdar SR, Marrie TJ. The value of prognostic indices for pneumonia. Curr Infect Dis Rep. 2008;10:215–22.View ArticlePubMedGoogle Scholar
  13. Lim WS. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003;58:377–82.View ArticlePubMedPubMed CentralGoogle Scholar
  14. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165–228.View ArticlePubMedGoogle Scholar
  15. Bretonnière C, Leone M, Milési C, Allaouchiche B, Armand-Lefevre L, Baldesi O, et al. Strategies to reduce curative antibiotic therapy in intensive care units (adult and paediatric). Intensive Care Med. 2015;41:1181–96.View ArticlePubMedGoogle Scholar
  16. Shindo Y, Ito R, Kobayashi D, Ando M, Ichikawa M, Goto Y, et al. Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2013;188:985–95.View ArticlePubMedGoogle Scholar
  17. Chidiac C, la Société de pathologie infectieuse de langue Française. Antibiothérapie par voie générale dans les infections respiratoires basses de l’adulte. Pneumonie aiguë communautaire. Exacerbations de bronchopneumopathie chronique obstructive. Médecine Mal Infect. 2011;41:221–8.View ArticleGoogle Scholar
  18. Bohte R, van Furth R, van denBroek PJ. Aetiology of community-acquired pneumonia: a prospective study among adults requiring admission to hospital. Thorax. 1995;50:543–7.View ArticlePubMedPubMed CentralGoogle Scholar
  19. The British Thoracic Society Research Committee and The Public Health Laboratory Service. The aetiology, management and outcome of severe community-acquired pneumonia on the intensive care unit. Respir Med. 2012;86:7–13.Google Scholar
  20. Woodhead M. Community-acquired pneumonia in Europe: causative pathogens and resistance patterns. Eur Respir J. 2002;36(Suppl):20–7.View ArticleGoogle Scholar
  21. Moine P, Vercken JB, Chevret S, Gajdos P. Severe community-acquired pneumonia. Etiology, epidemiology, and prognosis factors. French Study Group for Community-Acquired Pneumonia in the Intensive Care Unit. Chest. 1994;105:1487–95.View ArticlePubMedGoogle Scholar
  22. Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax. 2012;67:71–9.View ArticlePubMedGoogle Scholar
  23. Patterson JE. Antibiotic utilization: is there an effect on antimicrobial resistance? Chest. 2001;119(suppl):426–30.View ArticleGoogle Scholar
  24. Trecarichi EM, Cauda R, Tumbarello M. Detecting risk and predicting patient mortality in patients with extended-spectrum β-lactamase-producing Enterobacteriaceae bloodstream infections. Future Microbiol. 2012;7:1173–89.View ArticlePubMedGoogle Scholar
  25. Lim WS, Baudouin SV, George RC, et al. BTS guidelines for the management of community acquired pneumonia in adults: update. Thorax. 2009;64(Suppl 3):1–55.View ArticleGoogle Scholar
  26. Goffinet N, Lecadet N, Cousin M, Peron C, Hardouin JB, Batard E, et al. Increasing use of third-generation cephalosporins for pneumonia in the emergency department: may some prescriptions be avoided? Eur J Clin Microbiol Infect Dis. 2014;33:1095–9.View ArticlePubMedGoogle Scholar
  27. Khalil A, Metesky M, Klompas M, Muscedere J, Sweeney D, Palmer L, et al. Executive summary. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63:575–82.View ArticleGoogle Scholar

Copyright

© The Author(s) 2017

Advertisement