Yong Pil Chong

Viral Infection in Patients with Severe Pneumonia Requiring Intensive Care Unit Admission

RATIONALE The role of viruses in pneumonia in adults and the impact of viral infection on mortality have not been elucidated. Previous studies have significant limitations in that they relied predominantly on upper respiratory specimens. OBJECTIVES To investigate the role of viral infection in adult patients with pneumonia requiring intensive care unit (ICU) admission. METHODS A retrospective analysis of a prospective cohort was conducted in a 28-bed medical ICU. Patients with severe community-acquired pneumonia (CAP) or healthcare-associated pneumonia (HCAP) were included in the study. MEASUREMENTS AND MAIN RESULTS A total of 198 patients (64 with CAP, 134 with HCAP) were included for analysis. Of these, 115 patients (58.1%) underwent bronchoscopic bronchoalveolar lavage (BAL), 104 of whom were tested for respiratory viruses by BAL fluid reverse-transcription polymerase chain reaction (RT-PCR). Nasopharyngeal specimen RT-PCR was performed in 159 patients (84.1%). Seventy-one patients (35.9%) had a bacterial infection, and 72 patients (36.4%) had a viral infection. Rhinovirus was the most common identified virus (23.6%), followed by parainfluenza virus (20.8%), human metapneumovirus (18.1%), influenza virus (16.7%), and respiratory syncytial virus (13.9%). Respiratory syncytial virus was significantly more common in the CAP group (CAP, 10.9%; HCAP, 2.2%; P = 0.01). The mortalities of patients with bacterial infections, viral infections, and bacterial-viral coinfections were not significantly different (25.5, 26.5, and 33.3%, respectively; P = 0.82). CONCLUSIONS Viruses are frequently found in the airway of patients with pneumonia requiring ICU admission and may cause severe forms of pneumonia. Patients with viral infection and bacterial infection had comparable mortality rates.

Paradoxical responses in non-HIV-infected patients with peripheral lymph node tuberculosis

OBJECTIVES We evaluated the clinical characteristics and risk factors for the paradoxical response (PR) in non-HIV-infected patients with peripheral lymph node tuberculosis (TB). METHODS Medical records of non-HIV-infected patients aged > or =16 years with peripheral lymph node TB treated in a tertiary hospital between January 1997 and August 2007 were analysed. PR was defined as clinical or radiological worsening of pre-existing TB lesions, or development of new lesions in a patient who had received anti-TB therapy for at least 2 weeks. RESULTS Three hundred patients with lymph node TB were included. Of these, 235 patients (78%) had confirmed TB; the remaining 65 (22%) had probable TB and were excluded from the final analysis. Among the 235 study patients, their mean age (+/-standard deviation) was 37.6 (+/-13.9) years and 175 (75%) were female. PR occurred in 54 (23%; 95% confidence interval 18-28%) patients, at a median onset time of 8 weeks (interquartile range, 4-14 weeks) after starting anti-TB medication. In multivariate analysis, younger age (OR 0.96), male gender (OR 2.60), and the presence of local tenderness at the time of diagnosis (OR 2.90) were independently associated with PR. CONCLUSION PR was relatively common, occurring in one-fifth of non-HIV-infected patients with peripheral lymph node TB, and was associated with younger age, male gender, and the presence of local tenderness.

Persistent Staphylococcus aureus Bacteremia: A Prospective Analysis of Risk Factors, Outcomes, and Microbiologic and Genotypic Characteristics of Isolates

AbstractPersistent Staphylococcus aureus bacteremia (SAB) that fails to respond to appropriate antibiotic therapy is associated with poor outcomes. Comprehensive prospective studies on risk factors and outcomes of persistent bacteremia are limited. We investigated outcomes and risk factors encompassing clinical, pharmacokinetic, microbiologic, and genotypic characteristics associated with persistent bacteremia using a case-control study nested in a prospective cohort of patients with SAB at a tertiary-care hospital from August 2008 through September 2010. We compared the clinical characteristics, management, and outcomes of patients with persistent bacteremia (≥7 d) with controls with resolving bacteremia (<3 d). To detect associations between microbiologic and genotypic characteristics of methicillin-resistant S. aureus (MRSA) isolates and persistent bacteremia, we determined the heteroresistance phenotype, SCCmec type, agr genotype and functionality, multilocus sequence typing, and presence of 41 virulence genes. Our cohort consisted of 483 patients; 76 (15.7%) had persistent bacteremia, 212 (43.5%) had resolving bacteremia. In the multivariate analysis, independent risk factors associated with persistent bacteremia were community-onset bacteremia (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.24–6.87), bone and joint infection (OR, 5.26; 95% CI, 1.45–19.03), central venous catheter-related infection (OR, 3.36; 95% CI, 1.47–7.65), metastatic infection (OR, 36.22; 95% CI, 12.71–103.23), and methicillin resistance (OR, 16.99; 95% CI, 5.53–52.15). For patients with eradicable foci, delay (>3 d) in the removal of the infection focus was significantly associated with persistent bacteremia (OR, 2.18; 95% CI, 1.05–4.55). There were no significant associations of persistent bacteremia with high vancomycin minimal inhibitory concentration, vancomycin heteroresistance, and microbiologic/genotypic characteristics of MRSA isolates. However, initial vancomycin trough level <15 mg/L was an independent risk factor for persistent MRSA bacteremia (OR, 4.25; 95% CI, 1.51–11.96) in the multivariate analysis. Clinical outcomes were significantly worse for patients with persistent bacteremia. Relapse of bacteremia and attributable mortality within 12 weeks after SAB were significantly higher in patients with persistent bacteremia than in those with resolving bacteremia (9.2% [7/76] vs. 2.4% [5/212], p = 0.02 and 21.1% [16/76] vs. 9.4% [20/212], p = 0.009, respectively).In conclusion, patients with SAB should be given early aggressive treatment strategies, including early source control and maintenance of a vancomycin trough level ≥15 mg/L, to reduce the risk of persistent bacteremia.

Treatment Duration for Uncomplicated Staphylococcus aureus Bacteremia To Prevent Relapse: Analysis of a Prospective Observational Cohort Study

ABSTRACT Practice guidelines recommend at least 14 days of antibiotic therapy for uncomplicated Staphylococcus aureus bacteremia (SAB). However, these recommendations have not been formally evaluated in clinical studies. To evaluate the duration of therapy for uncomplicated SAB, we analyzed data from our prospective cohort of patients with SAB. A prospective observational cohort study was performed in patients with SAB at a tertiary-care hospital in Korea between August 2008 and September 2010. All adult patients with SAB were prospectively enrolled and observed over a 12-week period. Uncomplicated SAB was defined as follows: negative results of follow-up blood cultures at 2 to 4 days, defervescence within 72 h of therapy, no evidence of metastatic infection, and catheter-related bloodstream infection or primary bacteremia without evidence of endocarditis on echocardiography. Of 483 patients with SAB, 111 met the study criteria for uncomplicated SAB. Fifty-three (47.7%) had methicillin-resistant SAB. When short-course therapy (<14 days) and intermediate-course therapy (≥14 days) were compared, the treatment failure rates (10/38 [26.3%] versus 16/73 [21.9%]) and crude mortality (7/38 [18.4%] versus 16/73 [21.9%]) did not differ significantly between the two groups. However, short-course therapy was significantly associated with relapse (3/38 [7.9%] versus 0/73; P = 0.036). In multivariate analysis, primary bacteremia was associated with a trend toward increased treatment failure (P = 0.06). Therefore, in the treatment of uncomplicated SAB, it seems reasonable to consider at least 14 days of antibiotic therapy to prevent relapse, as practice guidelines recommend. Because of its poor prognosis, primary bacteremia, even with a low risk of complication, should not be treated with short-course therapy.

Comparison of the clinical features, bacterial genotypes and outcomes of patients with bacteraemia due to heteroresistant vancomycin-intermediate Staphylococcus aureus and vancomycin-susceptible S. aureus

OBJECTIVES We compared the clinical characteristics and outcomes of, and the bacterial genotypes in, patients with bacteraemia due to heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) and vancomycin-susceptible S. aureus (VSSA). METHODS A total of 268 consecutive patients with methicillin-resistant S. aureus (MRSA) bacteraemia were prospectively enrolled. All isolates were selected on the first day of bacteraemia and subjected to population analysis profiling for identification of hVISA phenotype and PCR analysis for 41 virulence factors. RESULTS Of 268 MRSA isolates, 101 (37.7%) were identified as hVISA. Overall mortality was similar in hVISA- and VSSA-infected patients (45/101 versus 65/167; P = 0.36). The following factors were independently associated with the presence of hVISA: a vancomycin MIC ≥2 mg/L by Etest [adjusted OR (aOR), 9.98; 95% CI, 4.22-23.59], rifampicin resistance (aOR, 5.74; 95% CI, 1.35-24.37), prior vancomycin therapy (aOR, 3.04; 95% CI, 1.49-6.17) and use of immunosuppressive therapy (aOR, 2.41; 95% CI, 1.12-5.17). Among patients with hVISA, bacteraemia was more likely to persist for ≥7 days in patients with an initial vancomycin trough <15 mg/L than in those with an initial trough ≥15 mg/L (13/34 versus 5/35; P = 0.02). The hVISA and VSSA isolates were genotypically similar. CONCLUSIONS The hVISA phenotype was present in more than one-third of MRSA isolates and was independently associated with several baseline factors. Although this phenotype did not affect patient outcomes, our results indicate that targeting an initial vancomycin trough of 15-20 mg/L may be beneficial in patients with hVISA bacteraemia.

Clinical significance of Propionibacterium acnes recovered from blood cultures : Analysis of 524 episodes

ABSTRACT Of 522 patients with Propionibacterium acnes bacteremia (PAB), 18 (3.5%) had clinically significant PAB. Of these 18 patients, 10 (55.6%) had hospital-acquired bacteremia and 6 (33.3%) had undergone invasive procedures before development of PAB. One patient with a ventricular septal defect presented with infective endocarditis. After the exclusion of 1 patient whose outcome was not available, the overall mortality rate was 5.9% (1/17).

Impact of adequate empirical combination therapy on mortality from bacteremic Pseudomonas aeruginosa pneumonia

BackgroundPseudomonas aeruginosa has gained an increasing amount of attention in the treatment of patients with pneumonia. However, the benefit of empirical combination therapy for pneumonia remains unclear. We evaluated the effects of adequate empirical combination therapy and multidrug-resistance in bacteremic Pseudomonas pneumonia on the mortality.MethodsA retrospective cohort study was performed at the 2,700-bed tertiary care university hospital. We reviewed the medical records of patients with bacteremic pneumonia between January 1997 and February 2011. Patients who received either inappropriate or appropriate empirical therapy were compared by using marginal structural model. Furthermore, we investigated the direct impact of combination therapy on clinical outcomes in patients with monomicrobial bacteremic pneumonia.ResultsAmong 100 consecutive patients with bacteremic Pseudomonas pneumonia, 65 patients were classified in the adequate empirical therapy group, 32 of whom received monotherapy and 33 combination therapy. In the marginal structural model, only inadequate therapy was significantly associated with 28-day mortality (p = 0.02), and multidrug-resistance was not a significant risk factor.To examine further the direct impact of combination therapy, we performed a subgroup analysis of the 65 patients who received adequate therapy. Multivariate logistic regression analysis identified absence of septic shock at the time of bacteremia (OR, 0.07; 95% CI, 0.01-0.49; p = 0.008), and adequate combination therapy (OR, 0.05; 95% CI, 0.01-0.34; p = 0.002) as variables independently associated with decreased all-cause 28-day mortality.ConclusionsOur study suggests that adequate empirical combination therapy can decrease mortality in patients with bacteremic Pseudomonas pneumonia.

Diagnostic usefulness of a T-cell-based assay for osteoarticular tuberculosis

BACKGROUND Although diagnosing osteoarticular tuberculosis (TB) remains a challenge, a recently developed Mycobacterium tuberculosis-specific ELISPOT assay for diagnosing TB infection has shown promising results. We performed a prospective, blinded, observational study to compare its diagnostic usefulness with those of conventional tests in patients with suspected osteoarticular TB. METHODS All patients presenting at a tertiary hospital between April 2008 and September 2009 with suspected osteoarticular TB were enrolled. In addition to conventional tests for TB, we used ELISPOT assays to measure the IFN-gamma response to ESAT-6 and CFP-10 in T-cells in samples of peripheral blood mononuclear cells (PBMC). Patients with suspected osteoarticular TB were classified by diagnostic category. RESULTS Of the 65 patients with suspected osteoarticular TB, 5 (8%) were excluded due to inconclusive diagnoses. Of the remaining 60 patients, 23 (38%) were classified as having confirmed TB, 3 (5%) as having probable TB, 2 (3%) as having possible TB, and 32 (53%) as not having active TB. Five (8%) patients with probable or possible TB were excluded from the final analysis. Of the 23 patients with confirmed osteoarticular TB, 15 (65%) had TB spondylitis, 4 (17%) had TB arthritis, 2 (9%) had prosthetic joint infection, and 2 (9%) had extra-spinal TB. The sensitivities of the tuberculin skin test (> or =10 mm) and the ELISPOT assay for active osteoarticular TB were 80% (95% confidence interval [CI], 58%-92%) and 100% (95% CI, 85%-100%) (P = 0.04), respectively and their specificities were 68% (95% CI, 51%-81%) and 58% (95% CI, 41%-74%) (P = 0.60), respectively. CONCLUSION A negative ELISPOT assay using PBMC may be a useful test for excluding a diagnosis of active osteoarticular TB.

Comparable Efficacy of Tigecycline versus Colistin Therapy for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Pneumonia in Critically Ill Patients

Tigecycline has in vitro activity against multidrug-resistant and extensively drug-resistant Acinetobacter baumannii (MDR/XDRAB), and may constitute an alternative therapy for treating pneumonia caused by MDR/XDRAB. The aim of this study was to compare the efficacy of tigecycline-based therapy with colistin-based therapy in patients with MDR/XDRAB pneumonia. Between January 2009 and December 2010, patients in the intensive care unit who were diagnosed with MDR/XDRAB pneumonia and treated with either tigecycline or colistin mono-/combination therapy were reviewed. A total of 70 patients were included in our analysis. Among them, 30 patients received tigecycline-based therapy, and 40 patients received colistin-based therapy. Baseline characteristics were similar in the two groups. Clinical success rate was 47% in the tigecycline group and 48% in the colistin group (P = 0.95). There were no differences between the groups with regard to other clinical outcomes, with the exception that nephrotoxicity was observed only in the colistin group (0% vs. 20%; P = 0.009). Clinical and microbiological success rates were numerically higher, and mortality rates were numerically lower in combination therapy group than in the monotherapy group. Multivariate analysis indicated that monotherapy was independently associated with increased clinical failure (aOR, 3.96; 95% CI, 1.03–15.26; P = 0.046). Our results suggest that tigecycline-based therapy was tolerable and the clinical outcome was comparable to that of colistin-based therapy for patients with MDR/XDRAB pneumonia. In addition, combination therapy may be more useful than monotherapy in treatment of MDR/XDRAB pneumonia.

Optimal Duration of Antibiotic Therapy in Patients With Hematogenous Vertebral Osteomyelitis at Low Risk and High Risk of Recurrence

BACKGROUND The optimal duration of antibiotic treatment for hematogenous vertebral osteomyelitis (HVO) should be based on the patients risk of recurrence, but it is not well established. METHODS A retrospective review was conducted to evaluate the optimal duration of antibiotic treatment in patients with HVO at low and high risk of recurrence. Patients with at least 1 independent baseline risk factor for recurrence, determined by multivariable analysis, were considered as high risk and those with no risk factor as low risk. RESULTS A total of 314 patients with microbiologically diagnosed HVO were evaluable for recurrence. In multivariable analysis, methicillin-resistant Staphylococcus aureus infection (adjusted odds ratio [aOR], 2.61; 95% confidence interval [CI], 1.16-5.87), undrained paravertebral/psoas abscesses (aOR, 4.09; 95% CI, 1.82-9.19), and end-stage renal disease (aOR, 6.58; 95% CI, 1.63-26.54) were independent baseline risk factors for recurrence. Therefore, 191 (60.8%) patients were classified as low risk and 123 (39.2%) as high risk. Among high-risk patients, there was a significant decreasing trend for recurrence according to total duration of antibiotic therapy: 34.8% (4-6 weeks [28-41 days]), 29.6% (6-8 weeks [42-55 days]), and 9.6% (≥8 weeks [≥56 days]) (P = .002). For low-risk patients, this association was still significant but the recurrence rates were much lower: 12.0% (4-6 weeks), 6.3% (6-8 weeks), and 2.2% (≥8 weeks) (P = .02). CONCLUSIONS Antibiotic therapy of prolonged duration (≥8 weeks) should be given to patients with HVO at high risk of recurrence. For low-risk patients, a shorter duration (6-8 weeks) of pathogen-directed antibiotic therapy may be sufficient.