Detection of associated bacteria in aspiration pneumonia and lung abscesses using partial 16S rRNA gene amplicon sequencing.

OBJECTIVES: Lower respiratory tract infections (LRTIs) are often caused by the patient's own oral commensal bacteria. Causative bacteria must be identified to select the appropriate antimicrobial agents; however, the pathogens are identified via routine culture methods in only approximately half of LRTI cases. METHODS: To investigate LRTI-associated bacteria, we conducted culture testing under aerobic and anaerobic conditions using culture-independent partial 16S rRNA gene amplicon sequencing analysis using a high-throughput sequencer in cases of aspiration pneumonia and lung abscesses. RESULTS: Culture testing of 17 aspiration pneumonia cases revealed Streptococcus spp. (n = 13), Prevotella spp. (n = 9), and Veillonella spp. (n = 8); 16S rRNA analysis of these cases yielded Streptococcus spp. (n = 16), Veillonella spp. (n = 12), Haemophilus spp. (n = 12), Prevotella spp. (n = 11), and Rothia spp. (n = 11). Culture testing of 8 lung abscess cases revealed Streptococcus spp. (n = 7) and Fusobacterium spp. (n = 4); 16S rRNA analysis of these cases yielded Fusobacterium spp. (n = 8), Prevotella spp. (n = 7), Streptococcus spp. (n = 6), and Porphyromonas spp. (n = 5). All taxa with abundance ratios of ≥50% on the 16S rRNA analysis were also detected in the cultures. However, several taxa were either undetected in the cultures despite relatively high abundance ratios on the 16S rRNA analysis or negative on the 16S rRNA analysis and isolated only by culturing. CONCLUSION: Our data provide a comprehensive list of bacterial taxa that may be associated with aspiration pneumonia and lung abscesses. In empirically treating LRTIs, this information will help determine the best treatment against the targeted anaerobes.

ASPIRATION BRONCHOPNEUMONIA BY ACINETOBACTER BAUMANNII IN A WILDLIFE EUROPEAN HARE (LEPUS EUROPAEUS) IN BRAZIL.

Acinetobacter baumannii is a major cause of illness in hospitalized patients and the most important and common pathogen in nosocomial outbreaks worldwide. In animals, A. baumannii has been associated with respiratory infections in a group of minks, leading to pneumonia and acute mortality. This report documents a case of aspiration bronchopneumonia in a wild European hare caused by A. baumannii. A free-ranging, adult male European hare was submitted to necropsy after acute trauma due to being hit by a car. Its lungs showed consolidation with abscess in the middle and cranial lobes. Histopathologic evaluation revealed liquefactive necrosis associated with neutrophilic infiltration, cellular debris, plant material, and bacterial myriads surrounded by moderate neutrophils, macrophages, multinucleated giant cells, lymphocytes, and plasma cell inflammation. Acinetobacter baumannii was isolated from lung tissue.

Antibiotics for Aspiration Pneumonia in Neurologically Impaired Children.

OBJECTIVE: To compare hospital outcomes associated with commonly used antibiotic therapies for aspiration pneumonia in children with neurologic impairment (NI). DESIGN/METHODS: A retrospective study of children with NI hospitalized with aspiration pneumonia at 39 children's hospitals in the Pediatric Health Information System database. Exposure was empiric antibiotic therapy classified by antimicrobial activity. Outcomes included acute respiratory failure, intensive care unit (ICU) transfer, and hospital length of stay (LOS). Multivariable regression evaluated associations between exposure and outcomes and adjusted for confounders, including medical complexity and acute illness severity. RESULTS: In the adjusted analysis, children receiving Gram-negative coverage alone had two-fold greater odds of respiratory failure (odds ratio [OR] 2.15; 95% CI: 1.41-3.27), greater odds of ICU transfer (OR 1.80; 95% CI: 1.03-3.14), and longer LOS [adjusted rate ratio (RR) 1.28; 95% CI: 1.16-1.41] than those receiving anaerobic coverage alone. Children receiving anaerobic and Gram-negative coverage had higher odds of respiratory failure (OR 1.65; 95% CI: 1.19-2.28) than those receiving anaerobic coverage alone, but ICU transfer (OR 1.15; 95% CI: 0.73-1.80) and length of stay (RR 1.07; 95% CI: 0.98-1.16) did not statistically differ. For children receiving anaerobic, Gram-negative, and P. aeruginosa coverage, LOS was shorter (RR 0.83; 95% CI: 0.76-0.90) than those receiving anaerobic coverage alone; odds of respiratory failure and ICU transfer rates did not significantly differ. CONCLUSIONS: Anaerobic therapy appears to be important in the treatment of aspiration pneumonia in children with NI. While Gram-negative coverage alone was associated with worse outcomes, its addition to anaerobic therapy may not yield improved outcomes.

Dynamics of microbiota during mechanical ventilation in aspiration pneumonia.

BACKGROUND: The emergence of multi-drug resistant pathogens is an urgent health-related problem, and the appropriate use of antibiotics is imperative. It is often difficult to identify the causative bacteria in patients with aspiration pneumonia because tracheal aspirate contains contaminants of oral bacteria. We investigated the dynamics of microbiota in mechanically ventilated patients with aspiration pneumonia to develop a treatment strategy. METHODS: Twenty-two intubated patients with aspiration pneumonia were recruited. Saliva and tracheal aspirate of the subjects were collected at three time points: (A) within 2 h after intubation, (B) just before administration of antibiotics, and (C) 48-72 h after administration of antibiotics. The microbiota in each specimen was analyzed by using the 16S rRNA gene clone library sequencing method. Bacterial floras of the samples were analyzed by principal component analysis. RESULTS: Principal component analysis based on the composition of genus revealed that although the changes of microbiota in the saliva from (A) to (B) were not clear, the composition of anaerobes in the tracheal aspirate (B) was lower than (A). In fact, the reduction of anaerobes, not in the saliva but in the tracheal aspirate from (A) to (B), was confirmed by incident rate ratios estimated by a multilevel Poisson regression model (p < 0.001). The extent of decrease in anaerobes was fully dependent on the time difference between the sampling of tracheal aspirate (A) and (B)-in particular, over 3 h of mechanical ventilation. This indicates that the alterations of microbiota (involving the reduction of anaerobes in the lower respiratory tract) occurred during mechanical ventilation prior to the administration of antibiotics. After the administration of antibiotics, Enterobacter spp., Corynebacterium spp., Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Granulicatera adiacens were predominantly detected in the tracheal aspirate (C). CONCLUSION: The microbiota of the lower respiratory tract changes dynamically during mechanical ventilation and during the administration of antibiotics in intubated patients with aspiration pneumonia. Antibiotics should be selected on the premise that dynamic changes in microbiota (involved in the reduction of anaerobes) may occur during the mechanical ventilation in these patients.

New perspectives in aspiration community acquired Pneumonia.

Introduction: Aspiration pneumonia is a subclass of community-acquired pneumonia that is expected to have an increasing contribution in mortality and morbidity, particularly in the elderly population over the next coming decades. While studies have revealed significant progress in identifying risk factors for aspiration pneumonia, the clinical presentation and diagnosis remain challenging to healthcare providers. Areas covered: We conducted a broad literature review using the MeSH heading in PubMed/MEDLINE of 'aspiration pneumonia' from January 1970 to July 2019. The understanding of the microbiology of aspiration pneumonia has evolved from a possible shift in the causative organisms away from anaerobes to traditional community-acquired pneumonia organisms. The importance of this shift is not yet known, but it has questioned the pathogenic role of anaerobes, appropriate anaerobic testing and the role of these pathogens in the pulmonary microbiome in patients with pneumonia. The identification of risk factors led to strategies to prevent or minimize the risk of aspiration pneumonia with moderate success. Expert opinion: Our expert opinion is that further research is needed to determine the role of the microbiome with aspiration pneumonia and patient risk factors. There is also a great need to develop clinical tools to help providers diagnose, treat, and prevent aspiration pneumonia.

Pilot study for risk assessment of aspiration pneumonia based on oral bacteria levels and serum biomarkers.

BACKGROUND: Aspiration pneumonia is a serious problem among elderly patients; it is caused by many risk factors including dysphagia, poor oral hygiene, malnutrition, and sedative medications. The aim of this study was to define a convenient procedure to objectively evaluate the risk of aspiration pneumonia in the clinical setting. METHODS: This prospective study included an aspiration pneumonia (AP) group, a community-acquired pneumonia (CAP) group, and a control (Con) group (patients hospitalized for lung cancer chemotherapy). We used the Oral Health Assessment Tool (OHAT), which assesses oral hygiene, and evaluated performance status, body mass index, serum albumin levels, substance P values in plasma, and oral bacterial counts. RESULTS: The oral health as assessed by the OHAT of the aspiration pneumonia group was significantly impaired compared with that of the CAP group and the control (5.13 ± 0.18, 4.40 ± 0.26, 3.90 ± 0.22, respectively; p < 0.05). The oral bacterial count in the aspiration pneumonia group (7.20 ± 0.11) was significantly higher than that in the CAP group (6.89 ± 0.12), consistent with the OHAT scores. Oral bacterial count was significantly reduced by oral care. CONCLUSIONS: OHAT and oral bacterial counts can be a tool to assess the requirement of taking oral care and other preventive procedures in patients at high risk of aspiration pneumonia.

[Microbiology of Aspiration Pneumonia].

The number of patients with pneumonia has been increasing as the population ages, and most fatal pneumonia cases are the elderly with aspiration pneumonia. Although aspiration pneumonia leads to poor short- and long-term prognosis, there have been no practical ways to diagnose it precisely. Persistent subclinical aspiration without any subjective symptoms is problematic in clinical practice in patients with aspiration pneumonia, and physicians can only use aspiration risks such as brain infarction to diagnose aspiration pneumonia. Anaerobes have been believed to be major causative pathogens in aspiration pneumonia, based on data from the 1970's. In relation to these data, Marik insisted that there is a possible overestimation of anaerobes because 1) the sampling of microbiologic specimens was in the late phase in the course of the illness, especially frequently after developing complications such as abscesses, necrotizing pneumonia, or empyema thoracis; 2) the organisms recovered by percutaneous transtracheal aspiration (PTA) sampling could have been contaminated by the aspiration of oropharyngeal flora during the PTA procedure or colonized in the trachea; and 3) many of the patients had chronic alcoholism or were under general anesthesia. In addition, 4) oral care was not common in the 1970s, and 5) the patients in these reports were relatively young. Molecular biological approaches using the 16S ribosomal RNA (rRNA) gene have recently been used, and have enabled us to detect more exact pathogens compared to conventional bacterial culture. Using the method with the detection of the 16S rRNA gene, we evaluated the bacterial phylotypes in bronchoalveolar lavage fluid in patients with aspiration pneumonia and found that oral streptococci were the most detected phylotypes (31.0%), while anaerobes were only 6.0%. Our results suggest that oral streptococci are important, and anaerobes may have been overestimated as causative pathogens in patients with aspiration pneumonia.

Aerodigestive sampling reveals altered microbial exchange between lung, oropharyngeal, and gastric microbiomes in children with impaired swallow function.

BACKGROUND: Children with oropharyngeal dysphagia have impaired airway protection mechanisms and are at higher risk for pneumonia and other pulmonary complications. Aspiration of gastric contents is often implicated as a cause for these pulmonary complications, despite being supported by little evidence. The goal of this study is to determine the relative contribution of oropharyngeal and gastric microbial communities to perturbations in the lung microbiome of children with and without oropharyngeal dysphagia and aspiration. METHODS: We conducted a prospective cohort study of 220 patients consecutively recruited from a tertiary aerodigestive center undergoing simultaneous esophagogastroduodenoscopy and flexible bronchoscopy. Bronchoalveolar lavage, gastric and oropharyngeal samples were collected from all recruited patients and 16S sequencing was performed. A subset of 104 patients also underwent video fluoroscopic swallow studies to assess swallow function and were categorized as aspiration/no aspiration. To ensure the validity of the results, we compared the microbiome of these aerodigestive patients to the microbiome of pediatric patients recruited to a longitudinal cohort study of children with suspected GERD; patients recruited to this study had oropharyngeal, gastric and/or stool samples available. The relationships between microbial communities across the aerodigestive tract were described by analyzing within- and between-patient beta diversities and identifying taxa which are exchanged between aerodigestive sites within patients. These relationships were then compared in patients with and without aspiration to evaluate the effect of aspiration on the aerodigestive microbiome. RESULTS: Within all patients, lung, oropharyngeal and gastric microbiomes overlap. The degree of similarity is the lowest between the oropharynx and lungs (median Jensen-Shannon distance (JSD) = 0.90), and as high between the stomach and lungs as between the oropharynx and stomach (median JSD = 0.56 for both; p = 0.6). Unlike the oropharyngeal microbiome, lung and gastric communities are highly variable across people and driven primarily by person rather than body site. In patients with aspiration, the lung microbiome more closely resembles oropharyngeal rather than gastric communities and there is greater prevalence of microbial exchange between the lung and oropharynx than between gastric and lung sites (p = 0.04 and 4x10-5, respectively). CONCLUSIONS: The gastric and lung microbiomes display significant overlap in patients with intact airway protective mechanisms while the lung and oropharynx remain distinct. In patients with impaired swallow function and aspiration, the lung microbiome shifts towards oropharyngeal rather than gastric communities. This finding may explain why antireflux surgeries fail to show benefit in pediatric pulmonary outcomes.

Antimicrobial susceptibilities of clinical isolates of the anaerobic bacteria which can cause aspiration pneumonia.

Aspiration pneumonia is an infectious disease of the lungs caused by inhalation of saliva or foods, associated with swallowing dysfunction. Therefore, the major causative organisms are oral or gastric bacteria. In this study, we evaluated the antimicrobial susceptibility patterns of the anaerobic bacteria which can cause aspiration pneumonia, Fusobacterium spp., Finegoldia magna, Bacteroides fragilis, Peptostreptococcus spp., Prevotella spp., and Streptococcus milleri group to ceftriaxone, cefmetazole, flomoxef, ampicillin/sulbactam, and ampicillin. We also tested the ß-lactamase activities of each of the bacterial strains. Fusobacterium spp. and Finegoldia magna were susceptible to all of the tested antimicrobial drugs, except ampicillin, and showed no ß-lactamase activity. The Streptococcus milleri group, Bacteroides fragilis, and Peptostreptococcus spp. showed decreased susceptibility to cefmetazole or flomoxef as compared to the susceptibility levels documented in a previous report. There was one strain of Peptostreptococcus anaerobius which was not susceptible to ampicillin/sulbactam, but also showed no ß-lactamase activity, suggesting that this strain harbored a mechanism of resistance other than the production of ß-lactamase. The susceptibility of Prevotella spp. to ceftriaxone was also decreased as compared to the susceptibility level documented in a previous report. Furthermore, ß-lactamase-positive strains were found even among ceftriaxone-susceptible strains. Elderly persons with swallowing dysfunction carry a risk of recurrent episodes of aspiration pneumonia and repeated use of antibiotics increases the risk of development of antibiotic resistance. In the present study, the antibiotic susceptibilities of some of organisms which can cause aspiration pneumonia were found to be decreased as compared to the susceptibility levels documented in a previous report. Therefore, surveillance of the antimicrobial susceptibility patterns of these bacteria is recommended to prevent the development of resistance.

Clinical observation of tongue coating of perioperative patients: factors related to the number of bacteria on the tongue before and after surgery.

BACKGROUND: Increased amount of tongue coating has been reported to be associated with increased bacteria count in the saliva and aspiration pneumonia in elderly people. However, the implications of tongue coating for prevention of postoperative complications in patients undergoing major oncologic or cardiac surgery has not been well documented. The purpose of this study is to investigate the number of bacteria on the tongue before and after surgery and factors affecting it. METHODS: Fifty-four patients who underwent oncologic or cardiac surgery under general anesthesia at Nagasaki University Hospital were enrolled in the study. Various demographic, tumor-related, treatment-related factors, and the number of bacteria on the tongue and in the saliva were examined, and the relationship among them was analyzed by Mann-Whitney U test, Spearman rank correlation coefficient, or multiple regression. RESULTS: Before surgery, no significant factors were correlated with the number of bacteria on the tongue, and there were no relationship between bacteria count on the tongue and that in the saliva. On the next day after surgery, bacteria on the tongue increased, and sex, periodontal pocket depth, feeding condition, dental plaque, blood loss, and bacteria in the saliva were correlated with bacteria on the tongue by a univariate analysis. A multivariate analysis showed that feeding condition, and amount of dental plaque were correlated with the number of bacteria. CONCLUSIONS: Increased number of bacteria on the tongue was associated with feeding condition and amount of dental plaque. Further studies are necessary to clarify the clinical significance of dental coating in perioperative oral management of patients undergoing oncologic or cardiac surgery.

Antibacterial treatment of aspiration pneumonia in older people: a systematic review.

BACKGROUND: Aspiration pneumonia is a common problem in older people with high mortality and increasing prevalence. OBJECTIVE: The aims of this paper were to systematically review the literature on the antibacterial treatment of aspiration pneumonia in elderly patients and identify the microbiology of aspiration pneumonia. MATERIALS AND METHODS: EMBASE, MEDLINE, and Cochrane databases were systematically searched for studies that examined the clinical efficacy of antibiotic treatment in elderly patients with aspiration pneumonia. Information on study design, antibiotic treatment, study population, participants, microbiology, clinical outcomes, adverse events, and mortality was recorded. RESULTS: There were no definitive clinical trials, placebo-controlled trials, or meta-analyses. Of the eight studies selected for inclusion in the review, the majority utilized and/or compared broad-spectrum antibiotics. No specific antibacterial agent had evidence of superior efficacy. Broad-spectrum antibiotics resulted in the emergence of multiresistant organisms. Anaerobic bacteria were infrequently isolated, suggesting a less important role in the pathogenesis of aspiration pneumonia. CONCLUSION: There is limited evidence with regard to the use of antibiotics in older patients with aspiration pneumonia. Research providing an evidence base for the treatment of aspiration pneumonia in older people is required.

Mycobacterium Fortuitum infection associated with achalasia.

The association between achalasia and no tuberculosis mycobacterial   lung infection is well described in the literature. MycobactériumFortuitum is often responsible, and the clinical's presentation   is an aspiration pneumonia resistant to usual antibiotic therapy. We report the case of a 15 year-old patient with the history of Allgrove syndrome. The chest imaging showed right lung congestion; the diagnosis was bacteriological and MycobactériumFortuitum resistant to rifampicin, isoniazid, pyrazinamide and ethambutol was isolated. The patient was treated by the association cotrimoxazole, ciprofloxacin and clarithromycin for 12 months and the clinical, radiological and bacteriological outcomes were favorable. To prevent the recurrence the patient benefited from a cardiomyotomy.

Retrospective analysis of incidence, clinical features, potential risk factors, and prognostic indicators for aspiration pneumonia in three brachycephalic dog breeds.

OBJECTIVE To investigate incidence, clinical features, potential risk factors, and prognostic indicators for aspiration pneumonia in Pugs, French Bulldogs, and Bulldogs. DESIGN Retrospective, observational study. ANIMALS 41 brachycephalic dogs with aspiration pneumonia. PROCEDURES Medical records of a veterinary referral hospital were retrospectively searched to identify Pugs, French Bulldogs, and Bulldogs treated for aspiration pneumonia between 2006 and 2015. Signalment, clinical data, and outcomes were recorded. Variables of interest were analyzed for statistical associations with outcome. Incidence of aspiration pneumonia for the population of interest was compared with that for all other dog breeds and for the general hospital population of dogs during the study. RESULTS 41 of 2,141 (1.91%) dogs of the selected brachycephalic breeds and 396 of 80,137 (0.49%) dogs overall had a diagnosis of aspiration pneumonia. Relative risk of the disease in the population of interest was 3.77 times that for all other breeds. Median age at disease onset was greater for Pugs (83 months) than for French Bulldogs (8 months) and Bulldogs (6 months). History of gastrointestinal signs was the most commonly observed preidentified risk factor (27/41 [66%]) in these breeds. Neurologic disease was significantly more common in Pugs than in French Bulldogs and Bulldogs. On univariate analysis, increased age, male sex, obtundation, hypoalbuminemia, azotemia, and high liver enzyme activities were associated with nonsurvival; on logistic regression, increased age was associated with nonsurvival. CONCLUSIONS AND CLINICAL RELEVANCE Age at onset and presence of other risk factors for aspiration pneumonia may vary among brachycephalic dog breeds. Prospective studies are needed to determine common risk factors and prognostic indicators for aspiration pneumonia in the larger population of brachycephalic dogs.

Murine Oropharyngeal Aspiration Model of Ventilator-associated and Hospital-acquired Bacterial Pneumonia.

Murine infection models are critical for understanding disease pathogenesis and testing the efficacy of novel therapeutics designed to combat causative pathogens. Infectious pneumonia is among the most common infections presented by patients in the clinic and thus warrants an appropriate in vivo model. Typical pneumonia models use intranasal inoculation, which deposits excessive organisms outside the lung, causing off-target complications and symptoms, such as sinusitis, gastritis, enteritis, physical trauma, or microparticle misting to mimic aerosol spread more typical of viral, tuberculous, or fungal pneumonia. These models do not accurately reflect the pathogenesis of typical community- or healthcare-acquired bacterial pneumonia. In contrast, this murine model of oropharyngeal aspiration pneumonia mimics the droplet route in healthcare-acquired pneumonia. Inoculating 50 µL of the bacteria suspension into the oropharynx of anesthetized mice causes reflexive aspiration, which results in pneumonia. With this model, one can examine the pathogenesis of pneumonia-causing pathogens and new treatments to combat these diseases.

Hypervirulent Klebsiella pneumoniae, a 5-year study in a French ICU.

PURPOSE: Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a leading cause of severe community-acquired pneumonia, liver abscess and disseminated infection in the Far East. Data regarding the incidence, clinical features and microbiological characteristics related to hvKp infections in the Western world are scarce. METHODOLOGY: The incidence, clinical features and microbiological characteristics of hvKp infections were investigated through a 5-year survey conducted in a single French intensive care unit. K. pneumoniae strains were screened for hypermucoviscosity based on a string test. Multilocus sequence typing and multiplex PCR analysis targeting virulence genes were performed on string test-positive strains. RESULTS: Over a 53-month period, a total of 59 infections due to K. pneumoniae were identified including 26 community-onset infections. Twelve hvKp infections were documented, accounting for 46.1 % of community-acquired K. pneumoniae. Community-acquired pneumonia (n=6), aspiration pneumonia (n=4) and liver abscess (n=2) represented initial sites and mode of infection. Compared to non-hvKp infections, patients with hvKp infections displayed higher rates of multi-organ failure (83.3 % vs 35.7 %; P=0.04), but mortality rates were not different (50 % vs 35 %; P=0.71). Strains K1/ST23 (n=5) and K2/ST86 (n=5) predominated. All hvKp strains displayed wild-type susceptibility. CONCLUSION: hvKp represent a potentially underestimated cause of fatal infections in the Western world.

Microbiology and prognosis assessment of hospitalized patients with aspiration pneumonia: a single-center prospective cohort study.

Aspiration pneumonia has a high incidence in hospitalized patients with community-acquired pneumonia and results in high mortality rates. We aimed to evaluate microbiology and assess prognostic factors of aspiration pneumonia in the setting of a tertiary hospital pulmonology department. Community-acquired (CAAP) and healthcare-associated aspiration pneumonia (HCAAP) cases hospitalized over a period of a year were prospectively followed. Demographic, clinical, biological and radiological data were recorded at admission, while sputum, tracheal aspirates or bronchial washing samples were collected within 48 hours of admission. During hospital stay, therapeutic and supportive measures and resulting complications were recorded. Regression analysis was applied to find statistically significant prognostic factors. The sample consisted of 70 patients (67.1% men); 55.7% of them presented as HCAAP; 94.3% had positive culture of lower respiratory tract specimens with isolation of 115 pathogens, 47 of which were multidrug- or extensively drug-resistant. The most common pathogens were Pseudomonas aeruginosa (37.1%), Klebsiella pneumoniae (27.1%), Staphylococcus aureus (25.7%) and Acinetobacter baumannii (20%). Empiric antimicrobial therapy was combination therapy in 70% and included antipseudomonal and MRSA-targeted antibiotics in 61.4% and 11.4%, respectively. Patients in the HCAAP group had a higher rate of antibiotics usage in the previous trimester, more frequent isolation of resistant strains and were more likely to receive inadequate empiric treatment than those in the CAAP group. In-hospital mortality was 52.2%; no difference between groups was noted. Independent factors of increased mortality were older age (p=0.004), low serum albumin levels (p=0.039), increased radiological involvement (p=0.050) and ineffective initial therapy (p=0.001). We concluded that patients hospitalized for aspiration pneumonia have frequent contact with healthcare services and acquire multidrug-resistant Gram-negative bacteria. Empiric therapy should target these specific microorganisms as its success determines the prognosis.