This was a hospital-based, prospective descriptive study. The study setting was Okinawa Chubu Hospital, which is located in the central area of Okinawa, a subtropical region of Japan. The University of Hawaii has supported the clinical education of the staff at this hospital with a Postgraduate Medical Education Program since 1966. Approximately 39,000 patients visit the emergency department annually and nearly 14,000 patients are hospitalized each year . Patients enrolled in the study attended between May 2013 and April 2014. All adult patients who were enrolled were suspected of a bacterial infection of the pulmonary system, urinary tract, or skin and soft tissue, and were newly admitted to the Division of Infectious Diseases through the emergency room. No other sites of infection were included in the study. These three infection sites constituted over 90 % of our hospitalized patients . The exclusion criteria were 1) diseases that were not included in the JAID/JSC Guide, such as pulmonary abscess, empyema, renal abscess, or prostate abscess; 2) more than one simultaneous site of infection, because this situation is not covered by the guidelines; 3) a diagnosis of something other than a bacterial infection when the culture results were received, because this study was only intended to compare the three most common sites of bacterial infection; and 4) all human immunodeficiency virus (HIV)-infected patients, because their clinical courses, such as Pneumocystis pneumonia, are quite different from those of community-acquired pneumonia. Infections that occurred after admission, such as Clostridium difficile-associated infections, were not included, for simplicity.
All patient information was collected from medical charts, including the types and doses of the antibiotics administered, all the bacteria isolated, changes in antibiotics after culture results, and the duration of antimicrobial use during hospitalization. All point-of-care Gram stains of sputum or urine samples were performed at the bedside by in-house staff members in the emergency room. Positive blood cultures were identified from the initial two sets of blood cultures. If the detected organisms were considered skin contaminants, the samples were classified as blood-culture negative.
According to the JAID/JSC Guide, pulmonary infection is classified as community-acquired pneumonia or aspiration pneumonia; urinary tract infection as pyelonephritis, complicated pyelonephritis, urosepsis, prostatitis, or catheter-related pyelonephritis; skin and soft tissue infection as cellulitis, severe cellulitis, or methicillin-resistant Staphylococcus aureus (MRSA)-suspected cellulitis. We diagnosed urosepsis and severe cellulitis as present in patients with a systolic blood pressure of <90 mmHg upon arrival, or in patients who did not respond to the administration of intravenous fluid. Complicated pyelonephritis was considered if a patient had a neurogenic bladder, calculi, prostate hyperplasia, an anatomical defect, or diabetes mellitus, or if they took immune suppressants or were pregnant.
Penicillins and first- or second-generation cephalosporins were defined as narrow-spectrum antibiotics; piperacillin/tazobactum, fourth-generation cephalosporin, carbapenems, and vancomycin as broad-spectrum antibiotics; and all other antibiotics as intermediate-spectrum antibiotics.
In our hospital, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and anaerobes were differentiated in Gram-stained sputum by physicians in the emergency room . The first-choice antimicrobial was selected based on local antibiotic-resistance patterns, which are updated every year by the hospital’s Microbiology Laboratory.
In Gram-stained sputum, Gram-positive diplococci suggested S. pneumoniae, and ampicillin was selected . Small Gram-negative coccobacilli suggested H. influenzae, and a third-generation cephalosporin (cefotaxime or ceftriaxone) was selected . Gram-negative diplococci suggested M. catarrhalis, and ampicillin-sulbactam was selected . Gram-negative rods suggested Enterobacteriaceae, such as K. pneumoniae, and a second- or third-generation cephalosporin was selected . Small Gram-negative rods suggested P. aeruginosa, and an antipseudomonal agent, such as piperacillin, ceftazidime, imipenem, meropenem, ciprofloxacin, or tobramycin, was selected . Polymicrobial flora suggested the aspiration of oral anaerobes, and ampicillin-sulbactum was selected .
In Gram-stained urine, Gram-negative rods suggested Enterobacteriaceae, such as Escherichia coli or K. pneumoniae, and a second-generation cephalosporin, such as cefotiam, was selected . However, if a patient was at high risk of a drug-resistant organism, such as one expressing extended-spectrum beta-lactamases (ESBLs), cefmetazole or carbapenem was selected. Small Gram-negative rods suggested P. aeruginosa, and an antipseudomonal agent was selected . Gram-positive cocci in chains suggested Streptococcus or Enterococcus, and ampicillin or vancomycin was selected.
In skin and soft tissue infections, specimens were not usually collected unless a subcutaneous abscess developed. Cefazolin, which is effective for both Streptococcus and Staphylococcus, was selected. If the risk of MRSA infection was high, clindamycin or vancomycin was added. For immunocompromised hosts, such as those with liver cirrhosis, a third-generation cephalosporin was selected as they are effective for Gram-negative organisms, such as Vibrio or Aeromonas, and Gram positive organisms.
Within these classifications, we compared two groups: one group of patients whose antibiotic was selected based on the point-of-care Gram stain in this study, and the other group with a simulated choice of antibiotic and dosage based on the Japanese guidelines.
The types of antimicrobials selected based on the Gram stain were real, whereas those based on the guidelines were simulated.
The evaluation of their effectiveness was based on culture results. If the cultured pathogen was susceptible in vitro and the clinical response was also favorable, the initially chosen antibiotic was continued or its spectrum narrowed down, and it was classified as “effective”. If the cultured pathogen was resistant in vitro and the clinical response was also unfavorable, a narrow-spectrum antibiotic was changed to a broader-spectrum antibiotic, and it was classified as “ineffective”. If the cultured pathogen was resistant in vitro, but effective in vivo, it was classified as “unknown”. If the culture result showed normal flora in the sputum or was negative, the effectiveness was evaluated from the clinical course. If a narrow-spectrum antimicrobial was effective, we considered that a broader antimicrobial in the simulation would automatically be effective. If this estimation was impossible, we considered it “unknown”.
The total antibiotic cost during hospitalization was determined using the original pharmaceutical price in Japanese yen, determined by the Ministry of Health, Labour and Welfare in Japan, and the days of intravenous antibiotic use.
Gram-stain-based antimicrobial therapy is the standard care at our hospital. This was an observational study, so written informed patient consent was deemed unnecessary. The study proposal was approved by the Institutional Review Board of Okinawa Chubu Hospital.
For continuous valuables, the means and standard deviations were described for normal distributions, and the medians and interquartile ranges were described for skewed distributions. The χ2 test or Fisher’s exact test was used to analyze categorical variables, and were calculated with the Stata software (version 12.1; StataCorp, College Station, TX, USA).