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Treatment recommendations of hospital-acquired pneumonia in Asian countries: first consensus report by the Asian HAP Working Group

2008; Elsevier BV; Volume: 36; Issue: 4 Linguagem: Inglês

10.1016/j.ajic.2007.01.015

1527-3296

Jae‐Hoon Song,

Antibiotic Resistance in Bacteria

Many different treatment options are available for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), which are important causes of morbidity and mortality. Although guidelines for the diagnosis and treatment of HAP and VAP have been published by various American and European societies, these guidelines may not be applicable in all respects to the diagnosis and treatment of HAP and VAP in Asian countries. In addition, clinical practice may vary among Asian countries, due to such factors as availability of specific antibiotics and formulations and their relative cost. In addition, and in particular, different epidemiologic, etiologic, and resistance patterns in Asian countries may affect treatment choices compared with those in Western countries. To address these issues, the Asian-Pacific Research Foundation for Infectious Diseases, together with the Asian Network for Surveillance of Resistant Pathogens, organized the Asian HAP Working Group to discuss current clinical practices and develop consensus treatment recommendations for HAP in Asian countries. The consensus treatment recommendations, summarized herein, represent the findings of an expert panel comprising 30 representatives from 10 Asian countries. Many different treatment options are available for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), which are important causes of morbidity and mortality. Although guidelines for the diagnosis and treatment of HAP and VAP have been published by various American and European societies, these guidelines may not be applicable in all respects to the diagnosis and treatment of HAP and VAP in Asian countries. In addition, clinical practice may vary among Asian countries, due to such factors as availability of specific antibiotics and formulations and their relative cost. In addition, and in particular, different epidemiologic, etiologic, and resistance patterns in Asian countries may affect treatment choices compared with those in Western countries. To address these issues, the Asian-Pacific Research Foundation for Infectious Diseases, together with the Asian Network for Surveillance of Resistant Pathogens, organized the Asian HAP Working Group to discuss current clinical practices and develop consensus treatment recommendations for HAP in Asian countries. The consensus treatment recommendations, summarized herein, represent the findings of an expert panel comprising 30 representatives from 10 Asian countries. Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are serious diseases that are often difficult to treat in clinical practice, resulting in high rates of morbidity and mortality worldwide. Many different treatment options are available. Currently available guidelines for diagnosis and treatment include those prepared by a joint committee of the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA)1American Thoracic Society, Infectious Disease Society of America Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.Am J Resp Crit Care Med. 2005; 171: 388-416Crossref PubMed Scopus (5327) Google Scholar and by the British Thoracic Society.2British Thoracic Society Standards of Care Committee BTS Guidelines for the management of community-acquired pneumonia in adults.Thorax. 2001; 56: IV1-IV64PubMed Google Scholar Although many Asian clinicians follow the general recommendations of the ATS/IDSA guidelines, others follow institutional recommendations or national guidelines when available. Several issues have greater relevance to infectious disease practice in Asian countries compared with other countries; these include, among others, variations in practice due to the epidemiology of HAP, prevalence of multidrug-resistant (MDR) pathogens, practice of antibiotic use, and availability, formulation, and cost of antibiotics. In particular, antimicrobial resistance patterns in Asia may be quite different from those found in the United States and other Western countries, with markedly higher incidences of methicillin-resistant Staphlyococcus aureus (MRSA) and MDR pathogens. Some of the most serious pathogens are multidrug- or pandrug-resistant Pseudomonas aeruginosa and Acinetobacter strains, which are resistant to most available treatments. Antimicrobial resistance can lead to inappropriate use of antimicrobial agents, such as overly frequent use or misuse, resulting in more resistance as well as clinical treatment failure. The prevalence of these pathogens has global significance, and this topic is of timely importance for practicing clinicians throughout the Asia-Pacific region. Recently, the Asian-Pacific Research Foundation for Infectious Diseases (ARFID), in conjunction with the Asian Network for Surveillance of Resistant Pathogens (ANSORP), organized the Asian HAP Working Group to discuss the consensus treatment recommendations for HAP in Asian countries based on the current epidemiologic situation in the region. The first working group meeting, held in Kuala Lumpur, Malaysia on April 22–23, 2006, brought together 30 physicians from 10 Asian countries (Malaysia, Thailand, China, South Korea, India, Taiwan, Hong Kong, Pakistan, Philippines, and Singapore). A list of participants is provided in the Appendix. A primary purpose of the meeting was to develop a consensus guideline regarding the best available practices for the treatment of HAP and VAP in these countries. Secondarily, the workshop aimed to further inform the recently published ATS/IDSA guidelines in regard to issues relevant to clinical practice in Asian countries. In this article, we summarize the consensus recommendations generated at this meeting. Existing governmental and institutional guidelines for the treatment of HAP and VAP in Asian countries, where available, were reviewed on an individual country or individual hospital basis. International guidelines for the treatment of HAP and VAP, including but not limited to the ATS/IDSA guidelines, also were considered, together with international epidemiologic data. Individual physicians representing 10 Asian countries supplemented this with national or local data on epidemiology, etiologic pathogens, diagnostic procedures, antimicrobial resistance, and empirical antimicrobial treatment regimens. Information regarding clinical practice issues in Asian countries was exchanged among the participants and critically analyzed. As the need for further data was identified, insofar as possible, such data were collected and added to the summary draft consensus recommendation. It was noted that knowledge gaps currently exist regarding evidence or data on the epidemiology, etiology, and antibiotic resistance of pathogens causing HAP and VAP in Asian countries. Evidence-based recommendations specific to clinical practice in Asia can be addressed in only certain areas of clinical practice. This situation is neither surprising nor new. The recent ATS/IDSA guidelines also acknowledge this limitation and emphasize VAP-related treatment issues, because fewer data are available regarding HAP in nonintubated patients. Nonetheless, the evaluation of the current evidence base, and the identification of areas of incomplete knowledge, is considered to be of value in itself to help shape the direction of future research studies. The expert consensus opinion achieved in the workshop and reported herein is considered an initial step in identifying the best available clinical practices in Asian hospitals. It is understood and expected that in the future, as more relevant data become available, these recommendations will be adapted and modified to reflect a changing evidence base. Only a few Asian countries have national guidelines for the antibiotic treatment of HAP and VAP (China, the Philippines, Hong Kong, and Taiwan). Two countries, the Philippines and Taiwan, are expected to publish national guidelines for the first time. Earlier guidelines used in Hong Kong (IMPACT guidelines) were updated in 2005.3Interhospital Multidisciplinary Program on Antimicrobial Chemotherapy. Reducing bacterial resistance with IMPACT (3rd ed). Hong Kong: 2005. p. 68. Adapted from Brown EM. Empirical antimicrobial therapy of mechanically ventilated patients with nosocomial pneumonia.J Antimicrob Chemother. 1997; 40: 463-468Crossref PubMed Scopus (13) Google Scholar National guidelines used in China are currently under revision.4Chinese Medical Association, Respiratory Branch Treatment guidelines for hospital-acquired pneumonia.Chin J Tuber Respir Dis. 1999; 22: 201-202Google Scholar Individual institutional guidelines from Singapore were reviewed; in addition, national guidelines from Singapore for the treatment of HAP have recently been made available. It was noted that many physicians in Asia are guided by the ATS/IDSA recommendations to greater or lesser degrees, and that some national guidelines (eg, Philippines, Taiwan) also adhere closely to the ATS/IDSA guidelines, with minor modifications. It was agreed that the availability of better surveillance data for HAP and VAP could facilitate the development of national treatment guidelines in many Asian countries. In general, the panel agreed with the initial approach to therapy proposed by previous guidelines (Fig 1).1American Thoracic Society, Infectious Disease Society of America Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.Am J Resp Crit Care Med. 2005; 171: 388-416Crossref PubMed Scopus (5327) Google Scholar Overall, 2 groups of patients are recognized in the initial treatment algorithm. One group, with early-onset HAP or VAP and no risk for MDR pathogens, has no need for broad-spectrum therapy. (In this context, early-onset HAP or VAP is considered HAP or VAP occurring within the first 4 days of hospitalization; late-onset HAP and VAP, that occurring 5 days or more after hospitalization.) Likely pathogens in early-onset HAP or VAP include Streptococcus pneumoniae, Haemophilus influenzae, MRSA, and antibiotic-susceptible enteric Gram-negative bacilli (ie, Escherichia coli, Klebsiella pneumoniae, Enterobacter species, Proteus species, or Serratia marcescens). Recommended treatment for this group is limited-spectrum antimicrobial therapy with either ceftriaxone, fluoroquinolone (levofloxacin, moxifloxacin, or ciprofloxacin), ampicillin-sulbactam, or ertapenem. The second group, with late-onset HAP or VAP or risk factors for MDR pathogens, requires broad-spectrum therapy. Late-onset HAP and VAP are more likely to be caused by MDR pathogens and are associated with increased morbidity and mortality. Risk factors for MDR pathogens include antimicrobial therapy within the preceding 90 days, current hospitalization of 5 days or longer, high frequency of antibiotic resistance in the community or specific hospital unit, admission from a health care–associated facility, and immunosuppressive disease or immunosuppressant therapy.1American Thoracic Society, Infectious Disease Society of America Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.Am J Resp Crit Care Med. 2005; 171: 388-416Crossref PubMed Scopus (5327) Google Scholar This group of patients is more likely to be infected by MDR pathogens (P. aeruginosa, extended-spectrum beta-lactamase [ESBL]+K. pneumoniae, Acinetobacter species, methicillin-resistant S. aureus, and Legionella pneumophila). The ATS/IDSA guidelines recommend combination broad-spectrum antibiotic therapy, using either antipseudomonal cephalosporin (cefepime, ceftazidime) or antipseudomonal carbepenem (impipenem or meropenem) or beta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam), along with either antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) or aminoglycoside (amikacin, gentamicin, or tobramycin). If MRSA is suspected, then linezolid or vancomycin is added to the other 2 drugs. If ESBL+K. pneumoniae or an Acinetobacter species is suspected, then carbepenem is considered a reliable choice. If L. pneumophila is suspected, then the combination regimen should include a macrolide (eg, azithromycin), or fluoroquinolone (ciprofloxacin or levofloxacin) should be used rather than aminoglycoside. The panel also agreed that the initial empirical antibiotic treatment choice should be guided by such factors as local microbiology and resistance patterns, drug availability and cost, and formulary restrictions on drugs in individual hospitals. These factors are also considered in existing guidelines, but they have greater relevance to practice in Asia, where in particular local microbiology and resistance patterns vary to a greater degree than in Western countries. Cost is also an issue of relatively greater significance for many patients treated by Asian doctors. Clinically, other factors that need to be weighed when selecting initial empirical antibiotic treatment include the results of lower respiratory tract (LRT) Gram stain, disease severity, medication allergies, and underlying comorbidities (eg, renal or hepatic insufficiency), and the impact of such agents on creating further resistance. LRT cultures may be made from samples obtained by endotracheal aspiration, bronchoalveolar lavage, or protected specimen brush. Although a positive culture cannot always distinguish a pathogen from a colonizing organism, a negative culture has utility in ruling out pneumonia and the presence of MDR pathogens, especially in intubated patients. The inclusion of disease severity in the treatment algorithm was discussed by the Working Group participants. Whereas previous ATS guidelines5American Thoracic Society Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy and preventative strategies.Am J Respir Crit Care Med. 1995; 153: 1711-1725Google Scholar considered disease severity in selecting treatment, current ATS/IDSA guidelines,1American Thoracic Society, Infectious Disease Society of America Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.Am J Resp Crit Care Med. 2005; 171: 388-416Crossref PubMed Scopus (5327) Google Scholar as well as national guidelines under development in Taiwan, do not consider this to be a factor. In an individual patient with severe pneumonia, the pneumonia may or may not be related to infection with an MDR pathogen. Although the etiologic agent (eg, methicillin-sensitive S. aureus) may be easily treated, the disease may manifest as severe if the host has a weakened immune response due to underlying comorbidities. Nonetheless, it is evident that many Asian physicians continue to regard disease severity as a significant issue in selecting initial empirical antibiotic treatment. In current guidelines, the presence of severe pneumonia is not considered a risk factor for MDR pathogens causing HAP and VAP. As always, clinical judgment is the best guide in the initial empirical selection of treatment. Multiple factors must be weighed, including the individual patient's overall status, timing of disease onset, local microbiologic data, underlying comorbidities, virulence of the suspected etiologic agent, and the presence of risk factors for MDR pathogens (Fig 1). Many clinicians in Asian countries would choose a single agent to treat early-onset HAP. The consensus recommendation of the panel includes several options and overlaps somewhat with existing guidelines (Table 1).1American Thoracic Society, Infectious Disease Society of America Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.Am J Resp Crit Care Med. 2005; 171: 388-416Crossref PubMed Scopus (5327) Google Scholar The third-generation cephalosporins (ceftriaxone or cefotaxime), fluoroquinolones (moxifloxacin, levofloxacin, and gatifloxacin), beta-lactam/beta-lactamase inhibitor combinations (amoxicillin/clavulanic acid or ampicillin/sulbactam), and ertapenem are recommended when monotherapy is indicated. Because the current knowledge base on the epidemiology and etiology of HAP in Asian countries is incomplete, the panel did not assign an order of priority in the selection of drug treatment. Rather, each of these options is considered more or less therapeutically equivalent to the others, providing coverage against many of the common potential pathogens causing HAP, including S. pneumoniae, H. influenzae, MRSA, and antibiotic-sensitive enteric Gram-negative bacilli. To some extent, the choice of agent should incorporate information on local microbiology. Therapy with a monobactam plus clindamycin or fluoroquinolone used alone is recommended for patients who are allergic to beta-lactam agents.Table 1Initial empirical antibiotic treatment for early-onset HAP: consensus recommendations by the Asian HAP Working GroupPotential pathogenRecommended regimen∗Antibiotic options should depend on the local epidemiology of etiologic pathogens.Streptococcus pneumoniae†The frequency of macrolide-resistant S. pneumoniae and MDR S. pneumoniae is increasing; levofloxacin or moxifloxacin are preferred to ciprofloxacin and the role of other new quinolones, such as gatifloxacin, has not been established.Haemophilus influenzaeMethicillin-sensitive Staphyloccocus aureusAntibiotic-sensitive enteric Gram-negative bacilli:Escherichia coliKlebsiella pneumoniaeEnterobacter speciesProteus speciesSerratia marcescensThird-generation cephalosporins (ceftriaxone, cefotaxime)orfluoroquinolones (moxifloxacin, levofloxacin)orβ-lactam/β-lactamase inhibitor (amoxicillin/clavulanic acid; ampicillin/sulbactam)orcarbepenems (ertapenem)orthird-generation cephalosporins plus macrolideormonobactam plus clindamycin (for β-lactam– allergic patients)∗ Antibiotic options should depend on the local epidemiology of etiologic pathogens.† The frequency of macrolide-resistant S. pneumoniae and MDR S. pneumoniae is increasing; levofloxacin or moxifloxacin are preferred to ciprofloxacin and the role of other new quinolones, such as gatifloxacin, has not been established. Open table in a new tab Another consideration for treating early-onset HAP is the use of combination therapy with a third-generation cephalosporin plus a macrolide (eg, azithromycin) or occasionally fluoroquinolone to provide broader initial coverage. The use of combination regimens for empirical therapy may have relevance in specific situations sometimes found in Asian countries. For example, in Pakistan, the etiologic distribution of pathogens causing early-onset HAP is very similar to that of community-acquired pneumonia (CAP), suggesting the need for a regimen providing coverage against atypical pathogens, and thus clarithromycin is often added for this purpose. Given the lack of objective data on the etiologic role of atypical pathogens in early-onset HAP, the panel discussed the need to collect better surveillance data regarding the incidence and prevalence of atypical pathogens in Asian countries and their role in early-onset HAP. To treat late-onset HAP in Asian countries, the panel primarily recommended using third- or fourth-generation cephalosporins (ceftazidime or cefepime), carbapenems (imipenem or meropenem) or piperacillin/tazobactam in combination with fluoroquinolones or aminoglycosides, plus/minus glycopeptides (vancomycin or teicoplanin) or linezolid (Table 2). Other regimens that may be considered by Asian clinicians include cefoperazone/sulbactam plus fluoroquinolones or aminoglycosides or ampicillin/sulbactam or fluoroquinolones (ciprofloxacin) plus aminoglycosides plus/minus glycopeptides (vancomycin or teicoplanin). The regimen containing antibiotics with sulbactam compound (cefoperazone/sulbactam or ampicillin/sulbactam) was especially recommended for the coverage of MDR Acinetobacter spp in some Asian countries.Table 2Initial empirical antibiotic treatment for late-onset HAP: consensus recommendations by the Asian HAP Working GroupPotential pathogenRecommended antibiotic regimenPathogens listed in Table 1 and MDR pathogensAntipseudomonal cephalosporin (cefepime, ceftazidime) Pseudomonas aeruginosaor Klebsiella pneumoniae (ESBL+)∗If an ESBL+ strain, such as K. pneumoniae, or an Acinetobacter species is suspected, then a carbepenem is a reliable choice. If L. pneumophila is suspected, then the combination antibiotic regimen should include a macrolide (eg, azithromycin), or a fluoroquinolone (eg, ciprofloxacin or levofloxacin) should be used rather than an aminoglycoside.antipseudomonal carbepene (imipenem or meropenem) Acinetobacter species∗If an ESBL+ strain, such as K. pneumoniae, or an Acinetobacter species is suspected, then a carbepenem is a reliable choice. If L. pneumophila is suspected, then the combination antibiotic regimen should include a macrolide (eg, azithromycin), or a fluoroquinolone (eg, ciprofloxacin or levofloxacin) should be used rather than an aminoglycoside.orbeta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam)MRSA+/−fluoroquinolone (ciprofloxacin or levofloxacin)oraminoglycoside (amikacin, gentamicin, or tobramycin)Legionella pneumophila∗If an ESBL+ strain, such as K. pneumoniae, or an Acinetobacter species is suspected, then a carbepenem is a reliable choice. If L. pneumophila is suspected, then the combination antibiotic regimen should include a macrolide (eg, azithromycin), or a fluoroquinolone (eg, ciprofloxacin or levofloxacin) should be used rather than an aminoglycoside.cefoperazone/sulbactam plus fluoroquinolones or aminoglycosides plus ampicillin/sulbactam (if sulbactam is not available)orfluoroquinolone (ciprofloxacin) plus aminoglycosidepluslinezolid or vancomycin†If MRSA risk factors are present or there is a high incidence locally.plusazithromycin or fluoroquinolone∗ If an ESBL+ strain, such as K. pneumoniae, or an Acinetobacter species is suspected, then a carbepenem is a reliable choice. If L. pneumophila is suspected, then the combination antibiotic regimen should include a macrolide (eg, azithromycin), or a fluoroquinolone (eg, ciprofloxacin or levofloxacin) should be used rather than an aminoglycoside.† If MRSA risk factors are present or there is a high incidence locally. Open table in a new tab As with early-onset HAP, the choice of therapy should be guided by local microbiology data. For example, in Korea or Taiwan, where MRSA is a relatively common pathogen found in late-onset HAP, a clinician might choose to add a glycopeptide (vancomycin or teicoplanin) or linezolid as the second drug, rather than a fluoroquinolone or an aminoglycoside. However, initial therapy with glycopeptides or linezolid is usually not recommended, because in late-onset HAP, up to 20% of etiologic pathogens may be MRSA, and the initial use of drugs directed against this pathogen may increase the likelihood of the emergence of vancomycin resistance in S. aureus or enterococci. Alternatively, the clinician might choose to ascertain the presence of Gram-positive cocci by Gram stain before adding vancomycin to therapy with a third-or fourth-generation cephalosporin. In the absence of Gram-positive cocci, vancomycin is not recommended. Some panel members stated a preference for levofloxacin, moxifloxacin, or gatifloxacin over ciprofloxacin for treating Acinetobacter, based on in vitro susceptibility data. Although there is no valid study on this approach, theoretically, aminoglycosides may have decreased bioavailability in the acidic environment of pneumonitis. The panel members agreed that use of ampicillin/sulbactam plus an aminoglycoside does appear to increase the response in some patients. A combination of two drugs containing sulbactam (eg, ampicillin/sulbactam and cefoperazone/sulbactam) may be used to deliver a higher dose of sulbactam. Alternatively, if sulbactam is available as a single agent (as it is in some countries), then the clinician may consider using it together with cefoperazone/sulbactam rather than adding ampicillin/sulbactam. It was noted that in some settings, Gram stain, with appropriate interpretation, can be used to confirm the presence of Acinetobacter baumannii. In the case of a confirmed infection, treatment with imipenem plus sulbactam as a single agent (if available) or plus ampicillin/sulbactam is recommended. In patients with early-onset VAP, the panel recommends, with no order of priority, fourth -generation cephalosporins such as cefepime or carbapenems (imipenem or meropenem) or piperacillin/tazobactam plus/minus fluoroquinolones or aminoglycosides, plus/minus glycopeptides (vancomycin or teicoplanin) or linezolid. Other regimens that may be considered include cefoperazone/sulbactam plus fluoroquinolones or aminoglycosides or ampicillin/sulbactam or fluoroquinolones (ciprofloxacin) plus aminoglycosides plus/minus the glycopeptides vancomycin or teicoplanin (Table 3). As in cases of late-onset HAP, the decision regarding which drug to add, either a fluoroquinolone or an aminoglycoside, and the decision of whether to add a glycopeptide or linezolid, is a matter of clinical judgment.Table 3Initial empirical antibiotic treatment for early-onset VAP: consensus recommendations by the Asian HAP Working GroupPotential pathogenRecommended antibiotic regimenPathogens listed in Table 1 and MDR pathogensAntipseudomonal cephalosporin (cefepime) Pseudomonas. Aeruginosaor Klebsiella pneumoniae (ESBL+)antipseudomonal carbepenem (imipenem or meropenem) Acinetobacter species†orMRSAbeta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam)+/−fluoroquinolone (ciprofloxacin or levofloxacin)oraminoglycoside (amikacin, gentamicin, or tobramycin)+/−linezolid or vancomycin Open table in a new tab Cefepime, a fourth-generation cephalosporin, was preferred to ceftazidime (see below) as an initial empirical agent for early-onset VAP. Cefpirome, another fourth-generation cephalosporin available in India, is a possible alternative to cefepime. Cefepime and cefpirome are more resistant to some beta-lactamases (ie, those that are plasmid- or chromosome-mediated) compared with third-generation cephalosporins. Cefepime and cefpirome, like ceftazidime, are active against P. aeruginosa and for this reason may be useful in early-onset VAP when there is a low risk for MDR pathogens. As always, the choice of agent should depend on local microbiology and resistance patterns. The panel noted that in some countries, third-generation cephalosporins are not recommended for initial empirical therapy in early-onset VAP. In particular, some organisms, including strains of ESBL+E. coli and K. pneumoniae and Acinetobacter, display increasing resistance to third-generation cephalosporins. In many Asian countries, there is a high prevalence of one or another of these organisms, all of which are major pathogens of HAP and VAP. For these reasons, ceftazidime is not recommended as initial empirical therapy. Ceftazidime has excellent activity against Pseudomonas, however, and its use (always in combination with other drugs) may be considered on a case-by-case basis in patients at low risk for MDR pathogens and early-onset VAP. On the other hand, the panel strongly recommended avoiding ceftazidime in patients at high risk for MDR pathogens and early-onset VAP with fever and leucopenia. Existing guidelines recommend the use of aminoglycosides rather than fluoroquinolones in a combination regimen with a beta-lactam agent. This recommendation is based on a study demonstrating a trend toward improved survival for patients receiving the aminoglycoside-containing combination but not the fluoroquinolone-containing combination.6Fowler R.A. Flavin K.E. Barr J. Weinacker A.B. Parsonnet J. Gould M.K. Variability in antibiotic prescribing patterns and outcomes in patients with clinically suspected ventilator-associated pneumonia.Chest. 2003; 123: 835-844Crossref PubMed Scopus (70) Google Scholar Among the aminoglycosides, in most Asian clinical settings, amikacin is preferred over gentamicin or tobramycin. Netilmicin, the latest of the aminoglycosides to be marketed, also may be considered. Netilmicin has broad antimicrobial activity against aerobic Gram-negative bacilli and is effective against Acinetobacter strains. Many Asian clinicians agree that fluoroquinolones also should be used judiciously. To prevent the emergence of resistant organisms to fluoroquinolones, some institutions have adopted a policy to reserve the use of ciprofloxacin for the treatment of enteric fever and related infections. Restriction of fluoroquinolone use can help maintain the susceptibility of bacterial organisms, which is another reason to select aminoglycosides for combination therapy. Local microbiology data and the circumstances of the individual patient always should be considered when planning treatment. If there is a high prevalence of a specific organism (eg, L. pneumophila), a combination regimen using a fluoroquinolone rather than an aminoglycoside may be preferred. In addition, fluoroquinolones are clearly a better choice in elderly patients and patients with decreased renal function. The panel concurred that ciprofloxacin and levofloxacin are the preferred fluoroquinolones. Ciprofloxacin is more effective than the other fluoroquinolones against P. aeruginosa, especially moxifloxacin. If nonfermenter strains other than Pseudomonas are suspected, then levofloxacin may be preferred. In cases of late-onset VAP, the panel recommended the use of carbapenems (imipenem or meropenem) or piperacillin/tazobactam in combination with fluoroquinolones or aminoglycosides plus/minus glycopeptides or linezolid (Table 4). Alt