Riad Khatib

Vancomycin MIC plus Heteroresistance and Outcome of Methicillin-Resistant Staphylococcus aureus Bacteremia: Trends over 11 Years

ABSTRACT Vancomycin MICs (V-MIC) and the frequency of heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) isolates are increasing among methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) isolates, but their relevance remains uncertain. We compared the V-MIC (Etest) and the frequency of hVISA (Etest macromethod) for all MRSA blood isolates saved over an 11-year span and correlated the results with the clinical outcome. We tested 489 isolates: 61, 55, 187, and 186 isolates recovered in 1996-1997, 2000, 2002-2003, and 2005-2006, respectively. The V-MICs were ≤1, 1.5, 2, and 3 μg/ml for 74 (15.1%), 355 (72.6%), 50 (10.2%), and 10 (2.1%) isolates, respectively. We detected hVISA in 0/74, 48/355 (13.5%), 15/50 (30.0%), and 8/10 (80.0%) isolates with V-MICs of ≤1, 1.5, 2, and 3 μg/ml, respectively (P < 0.001). The V-MIC distribution and the hVISA frequency were stable over the 11-year period. Most patients (89.0%) received vancomycin. The mortality rate (evaluated with 285 patients for whose isolates the trough V-MIC was ≥10 μg/ml) was comparable for patients whose isolates had V-MICs of ≤1 and 1.5 μg/ml (19.4% and 27.0%, respectively; P = 0.2) but higher for patients whose isolates had V-MICs of ≥2 μg/ml (47.6%; P = 0.03). However, the impact of V-MIC and hVISA status on mortality or persistent (≥7 days) bacteremia was not substantiated by multivariate analysis. Staphylococcal chromosome cassette mec (SCCmec) typing of 261 isolates (including all hVISA isolates) revealed that 93.0% of the hVISA isolates were SCCmec type II. These findings demonstrate that the V-MIC distribution and hVISA frequencies were stable over an 11-year span. A V-MIC of ≥2 μg/ml was associated with a higher rate of mortality by univariate analysis, but the relevance of the V-MIC and the presence of hVISA remain uncertain. A multicenter prospective randomized study by the use of standardized methods is needed to evaluate the relevance of hVISA and determine the optimal treatment of patients whose isolates have V-MICs of ≥2.0 μg/ml.

Persistence in Staphylococcus aureus bacteremia: Incidence, characteristics of patients and outcome

Staphylococcus aureus bacteremia often persists. The reasons for persistence and its outcome are poorly defined. We conducted a prospective-observational study among 245 consecutive S. aureus (MRSA: n=125; MSSA: n=120) bacteremias (≥1 positive blood cultures (BC)) among 234 adults (18–103-y-old; median = 59 y) hospitalized during 1 January 2002–31 December 2002 at a 600-bed teaching hospital. Measurements included bacteremia duration, complication-rate (metastatic infection, relapse or attributable mortality) and outcome. Bacteremia duration was measured based on follow-up BC among 193 patients and estimated based on symptoms resolution in the rest. Measured (1–59 d; median = 2) and estimated (median = 1 d) duration correlated (r=0.885) though positive follow-up BC was often detected without fever (57/105 patients, 54.3%). Persistence (defined as bacteremia for ≥3 d) was noted in 84 cases (38.4%). Complication-rate increased steadily with bacteremia duration (6.6%, 24.0% and 37.7% in bacteremia for 1–2, 3 and ≥4 d, respectively; p=0.05). Cox regression analysis revealed that bacteremia duration correlated positively with endovascular sources (p=0.006), vancomycin treatment (p=0.016), cardiovascular prosthesis (p=0.025), metastatic infections (p=0.025) and diabetes (p=0.038). It is concluded that persistent bacteremia is a feature of S. aureus infection, irrespective of oxacillin susceptibility, associated with worse outcome. Risk factors include endovascular sources, cardiovascular prosthesis, metastatic infections, vancomycin treatment and diabetes. Patients at risk may benefit from novel treatment strategies.

Herpes simplex virus esophagitis in the immunocompetent host: an overview

OBJECTIVE:The aim of this study was to delineate the characteristics of herpes simplex virus esophagitis (HSVE) in the immunocompetent host.METHODS:The study entailed a case report and a review of relevant literature through a MEDLINE search back to 1966. All cases with documented HSVE in patients without immunosuppression were selected and their characteristics defined.RESULTS:A total of 38 cases were identified. The age range was 1–76 yr and the male/female ratio 3.2/1. Antecedent exposure to HSV disease was described in eight cases (21.1%). A prodrome of systemic manifestations preceded the onset of esophageal symptoms in nine subjects (23.6%). Manifestations included acute odynophagia (76.3%), heartburn (50%), and fever (44.7%). Concurrent oropharyngeal lesions were uncommon (n = 8, 21.1%). Endoscopically, extensive involvement was common, showing friable mucosa (84.2%), numerous ulcers (86.8%), and whitish-exudates (39.5%). The distal esophagus was most commonly affected (63.8%). Microscopic examination showed characteristic viral cytopathology in 26 (68.4%) cases. Virus was recovered from esophageal-brushes or biopsies in 23 of 24 (95.8%) patients and immunocytochemistry was positive in seven of eight (87.5%) cases. Immune status was consistent with primary HSV infection in eight (21.1%) cases. The disease was self-limiting, although esophageal perforation and upper GI bleeding were reported in one case each.CONCLUSIONS:HSVE in the immunocompetent host is a rare but distinct entity, and is significantly more common in male subjects. It represents either primary infection or reactivation, and is characterized by acute onset, systemic manifestations, and extensive erosive-ulcerative involvement of the mid-distal esophagus. Histopathological examination alone may miss the diagnosis; adding tissue-viral culture optimizes the diagnostic sensitivity. It is usually self-limiting; whether antiviral therapy is beneficial remains unknown.

Cytomegalovirus Colitis in the Immunocompetent Host: an Overview

This paper describes 2 immunocompetent patients with cytomegalovirus colitis and reviews all previously reported cases (n = 13). Affected patients were generally older (69.13+/-15.62 y-old) with probable reactivation (n = 8) or younger (43.86+/-19.73 y-old) with probable primary infection (n = 7). The onset of illness was found to be hospital-associated in 4 (50.0%) reactivation cases and 1 (14.3%) primary case. Presenting manifestations included diarrhoea (86.7%), fever (80.0%), gastrointestinal bleeding (66.7%) and abdominal pain (60.0%). Endoscopy showed erosive colitis with multiple (n = 11; 73.3%) or single ulcers (n = 2, 13.3%); biopsy was diagnostic in 12/13 (92.3%) patients. Complications included massive haemorrhage (13.3%), toxic megacolon (13.3%), perforation (13.3%) and protracted inflammatory bowel disease (20.0%; exclusively in primary-infection). The mortality rate was 26.7%. Antiviral-agents were given in 8 (53.3%) cases; assessment of treatment-efficacy was not possible. In conclusion, cytomegalovirus colitis in the immunocompetent-host is a rare but potentially severe erosive disease with significant morbidity. It may occur during primary infection or reactivation; the diagnosis requires careful histopathological examination and the benefit of antiviral-therapy is unknown.

Time to Positivity in Staphylococcus aureus Bacteremia: Possible Correlation with the Source and Outcome of Infection

BACKGROUND Staphylococcus aureus bacteremia often persists and causes metastatic infections. It is unknown whether the time between blood culture incubation and growth detection (i.e., the time to positivity) in a continuously monitored system--a probable surrogate marker of bacteremia severity--correlates with outcome. METHODS We performed a prospective, observational study involving adult inpatients who had S. aureus bacteremia between 1 January 2002 and 30 June 2003 at a 600-bed teaching hospital. Measurements included time to positivity in initial blood culture series, duration of bacteremia, rate of metastatic infection, and outcome. RESULTS A total of 376 S. aureus bacteremias (> or = 1 positive blood culture result) were reported for 357 patients aged 18-103 years (median age, 59 years); 64 bacteremias were excluded because blood was drawn after antibiotic therapy was started (n = 59) or through an intravascular catheter (n = 5). The source of infection was identified in 244 series (78.2%). Metastatic infection was detected in 25 bacteremias (8.0%). The mortality rate was 25.6%. The duration of bacteremia (determined in 251 series) was 1-59 days (median duration, 1 day; 70th percentile, 3 days). The time to positivity ranged from 4.2 to 98.2 h (median time to positivity, 15.5 h) and was significantly shorter for patients with an endovascular source of infection (14.9+/-5.4 vs. 19.5+/-10.6 h; P < .0005), extended duration (i.e., > or = 3 days) of bacteremia (14.1+/-4.2 vs. 18.6+/-9.2 h; P < .0005), and metastatic infection (12.9+/-5.9 vs 18.0+/-9.3 h; P = .007). Analysis of a range of cutoff values demonstrated that a time to positivity of < or = 14 h yielded the best sensitivity and specificity for predicting the source and outcome of infection. Logistic regression analyses revealed that a time to positivity of < or = 14 h was an independent predictor of an endovascular source of infection (P < .0005), extended bacteremia (P < .0005), metastatic infection (P < .0005), and attributable mortality (P = .017). CONCLUSIONS Time to positivity in S. aureus bacteremia may provide useful diagnostic and prognostic information. Growth of S. aureus within 14 h after the initiation of incubation may identify patients with a high likelihood of endovascular infection sources, delayed clearance, and complications.

Peripherally inserted central venous catheters in the acute care setting: A safe alternative to high-risk short-term central venous catheters.

BACKGROUND Peripherally inserted central venous catheters (PICCs) serve as an alternative to short-term central venous catheters (CVCs) for providing intravenous (IV) access in the hospital. It is not clear which device has a lower risk of central line-associated bloodstream infection (CLABSI). We compared CVC- and PICC-related CLABSI rates in the setting of an intervention to remove high-risk CVCs. METHODS We prospectively followed patients with CVCs in the non-intensive care units (ICUs) and those with PICCs hospital-wide. A team evaluated the need for the CVC and the risk of infection, recommended the discontinuation of unnecessary or high-risk CVCs, and suggested PICC insertion for patients requiring prolonged access. Data on age, gender, type of catheter, duration of catheter utilization, and the development of CLABSIs were obtained. RESULTS A total of 638 CVCs were placed for 4917 catheter-days, during which 12 patients had a CLABSI, for a rate of 2.4 per 1000 catheter-days. A total of 622 PICCs were placed for 5703 catheter-days, during which 13 patients had a CLABSI, for a rate of 2.3 per 1000 catheter-days. The median time to development of infection was significantly longer in the patients with a PICC (23 vs 13 days; P=.03). CONCLUSION In the presence of active surveillance and intervention to remove unnecessary or high-risk CVCs, CVCs and PICCs had similar rates of CLABSIs. Given their longer time to the development of infection, PICCs may be a safe alternative for prolonged inpatient IV access.

Staphylococcus aureus Bacteremia: Compliance with Standard Treatment, Long-term Outcome and Predictors of Relapse

The long-term outcome of compliance with standard treatment recommendations for Staphylococcus aureus bacteremia was assessed. Cases of S. aureus bacteremia at our institution over a 2-y period were reviewed and follow-up performed by review of subsequent admissions or contact with primary care physicians. We encountered 226 cases (age 64.7±15.8 y) and most (171/226, 75.7%) had no removable source. In-hospital mortality rate was 32.7% (74/226). Follow-up of 104/152 (68.4%) survivors (for 386.7±449.8 d) revealed 23.1% (24/104) relapses: recurrent bacteremia (n=19), distant site (n=3) and local recurrence (n=2). Most relapses (21/24; 87.5%) occurred within 90 d of therapy. Relapse rate was higher with vancomycin treatment (20/48 vs. 4/56; p<0.001), bacteremia for ≥3 d (9/20 vs. 15/84; p=0.001), and failure to remove the source (6/7 vs. 6/22; p=0.006). Vancomycin effect was independent of oxacillin susceptibility. Treatment for less than the standard 2-week duration among 19 patients with short duration of bacteremia (<3 d) did not increase relapse rate (1/19; 5.3%). Duration of bacteremia, vancomycin therapy and failure to remove the source were predictors of relapse. Prospective studies are needed to determine if S. aureus bacteremias of short duration can be treated for 2 weeks or less, and define the optimal duration for prolonged bacteremia when vancomycin is used.

Frequency of Reduced Vancomycin Susceptibility and Heterogeneous Subpopulation in Persistent or Recurrent Methicillin-Resistant Staphylococcus aureus Bacteremia

Vancomycin susceptibility was checked in isolates from initial and final blood samples obtained from 22 patients with persistent or recurrent methicillin-resistant Staphylococcus aureus bacteremia. The minimum inhibitory concentration of vancomycin was determined using Etest and found to have increased in 2 pairs of isolates, and results of screening in 4 mu g vancomycin and a modified population analysis profile suggested heteroresistance in 3 isolates (13.6%). Heteroresistance is not a common cause of persistent or recurrent bacteremia.

Hepatic actinomycosis : An overview of salient features and outcome of therapy

A 34-y-old African-American male developed Actinomyces liver abscess 8 months after appendectomy. Review of the English language literature revealed 56 additional cases of hepatic actinomycosis. Affected patients were typically immunocompetent, had a wide age range (4-86 y) and were predominantly male (70.2%). Infection was frequently (80.7%) cryptogenic, presenting with fever (83.3%), abdominal pain (74.5%) and weight loss (50.9%) over a 3.7 ± 5.1 month period. The most common radiographic finding was a single hypodense mass/abscess (68.4%). Extension to surrounding tissues was evident in 19 cases (33.3%). Diagnosis was usually accomplished microscopically and culture was often (33.3%) negative. Infection was often (35.2%) mixed, usually with anaerobic bacteria. A surgical or percutaneous approach was diagnostic in 29/35 (82.9%) and 24/33 (72.7%) cases, respectively. The overall mortality rate was 8.8%; it was 10.7% with medical therapy alone and 4.0% using a combined medical/intervention approach (p = 0.6). In conclusion, hepatic actinomycosis is a rare subacute infection that may mimic neoplasm. It is usually cryptogenic, is more common among immunocompetent individuals and male subjects and is highly responsive to medical therapy.

Relevance of vancomycin-intermediate susceptibility and heteroresistance in methicillin-resistant Staphylococcus aureus bacteraemia

OBJECTIVES To assess the relevance of vancomycin-intermediate susceptibility (VISA) and heteroresistance (hVISA) in methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. METHODS We determined vancomycin MICs for 371 saved MRSA blood isolates (2002-03; 2005-06) by Etest and broth microdilution (BMD), screened for hVISA (Etest methods), determined the population analysis profile (PAP)/AUC for isolates with suspected reduced susceptibility (MICs >2 mg/L and/or hVISA-screen-positive versus Mu3 (hVISA control), and stratified patient characteristics and outcome according to susceptibility phenotype: VISA (PAP/AUC >1.3), hVISA (PAP/AUC 0.9-1.3), and susceptible (S-MRSA; PAP/AUC <0.9). RESULTS PAP/AUC revealed 6 (1.6%) VISA and 30 (8.1%) hVISA phenotypes. The Etest MIC was above the susceptibility cut-off (2 mg/L) for all VISA isolates, whereas the BMD MIC was within the susceptibility range in two (33.3%) instances. Eight hVISA isolates (26.7%) with MICs of 2 mg/L were hVISA-screen negative. SCCmec typing revealed SCCmec II in 100% of VISA, 86.7% of hVISA and 75.5% of S-MRSA isolates (P = 0.04). Prior vancomycin use was documented in 100% of VISA, 73.3% of hVISA and 52.2% of S-MRSA cases (P = 0.002). Outcome (compared in 243 vancomycin-treated patients with MICs of 2 mg/L) revealed longer time to clearance in VISA cases [12.1 ± 13.1 days versus 3.3 ± 3.9 (hVISA) and 3.7 ± 5.1 (S-MRSA); P = 0.001], more frequent endocarditis [33.3% versus 9.1% (hVISA; P = 0.1) and 4.2% (S-MRSA; P = 0.001)] and attributable mortality [33.3% versus 9.1% (hVISA; P = 0.1) and 8.4% (S-MRSA); P = 0.08]. CONCLUSIONS No adverse outcome was documented with hVISA phenotype, whereas VISA contributed to vancomycin treatment failure. VISA and hVISA appear to emerge in SCCmec II isolates among vancomycin-exposed patients and are better detected by Etest.