Fluoroquinolone resistance in Mycobacterium tuberculosis: the effect of duration and timing of fluoroquinolone exposure.

RATIONALE: Fluoroquinolones are the most commonly prescribed antibiotic class in the United States. They have the potential to become first-line antituberculosis therapy, but the effect of fluoroquinolone use on fluoroquinolone resistance in Mycobacterium tuberculosis is not well characterized. OBJECTIVES: To determine the prevalence of and risk factors for fluoroquinolone-resistant tuberculosis in a large United States population. METHODS: We identified all people with culture-confirmed tuberculosis enrolled in TennCare (Medicaid) and reported to the Tennessee Department of Health from January 2002 to December 2006. People with fluoroquinolone-resistant M. tuberculosis isolates (cases) were compared with those with susceptible isolates (control subjects). Fluoroquinolone resistance was determined by agar proportion using ofloxacin 2 microg/ml. Outpatient fluoroquinolone exposure in the 12 months before tuberculosis diagnosis was ascertained from TennCare pharmacy data. MEASUREMENTS AND MAIN RESULTS: Of 640 study patients, 116 (18%) had fluoroquinolone exposure in the 12 months before diagnosis, and 16 (2.5%; 95% confidence interval [CI], 1.4-4.0%) M. tuberculosis isolates were fluoroquinolone resistant. Among the 54 patients with more than 10 days of fluoroquinolone exposure, 7 (13%) had fluoroquinolone resistance. In multivariable logistic regression analyses using propensity score to control for age, sex, race, HIV serostatus, and site of disease, more than 10 days of fluoroquinolone exposure before tuberculosis diagnosis was associated with fluoroquinolone resistance (odds ratio 7.0; 95% CI, 2.3-20.6; P = 0.001). Fluoroquinolone exposure for more than 10 days that occurred more than 60 days before tuberculosis diagnosis was associated with the highest risk of resistance (20.8%; odds ratio 17.0; 95% CI, 5.1-56.8; P < 0.001 compared with no exposure). CONCLUSIONS: Overall, fluoroquinolone resistance was relatively low. However, receipt of fluoroquinolones for more than 10 days, particularly more than 60 days before tuberculosis diagnosis, was associated with a high risk of fluoroquinolone-resistant tuberculosis.

Compliance with azithromycin versus erythromycin in the setting of a pertussis outbreak.

BACKGROUND: Erythromycin has traditionally been the choice for prophylaxis and treatment of pertussis, but recently azithromycin has been recommended as another first-line agent. We evaluated treatment adherence between exposed persons giving erythromycin or azithromycin during a community-wide pertussis outbreak. METHODS: This was a case-control study. All cases and their contacts were prescribed either 56 doses of erythromycin over 14 days or 5 doses of azithromycin over 5 days. A standardized questionnaire regarding demographics, side effects, and compliance with therapy was administered by mail or telephone interviews. RESULTS: Of 244 persons prescribed erythromycin, 139 (57%) completed the full course compared with 234 (93%) of 251 persons prescribed azithromycin (rate ratio [RR] 4.5; 95% confidence interval [CI], 2.9-7.0). The primary reason for not completing erythromycin was side effects in 79 (76%) persons, of whom 72 (91%) reported gastrointestinal upset, compared with azithromycin side effects in 6 (35%) of whom 5 (83%) reported gastrointestinal side effects. CONCLUSIONS: Azithromycin was associated with significantly higher completion rates than erythromycin. Due to side effects, the use of azithromycin may be preferable to erythromycin in outbreaks of pertussis.

Fluoroquinolone resistance in Mycobacterium tuberculosis: an assessment of MGIT 960, MODS and nitrate reductase assay and fluoroquinolone cross-resistance.

OBJECTIVES: The aim of this study was to assess the sensitivity, specificity and time to results of mycobacterial growth indicator tube (MGIT) 960, microscopic observation drug susceptibility (MODS) assay and nitrate reductase assay (NRA) compared with the gold standard agar proportion method (PM), and to determine whether there is cross-resistance between older-generation fluoroquinolones and moxifloxacin. METHODS: Mycobacterium tuberculosis isolates from culture-confirmed tuberculosis patients from 2002 to 2007 were tested for ofloxacin (2 mg/L) resistance by PM and MGIT 960. All isolates from 2005 and 2006 were also tested by MODS and NRA. Ofloxacin-resistant isolates by PM were further tested by all four methods using ciprofloxacin, levofloxacin and moxifloxacin. For each ofloxacin-resistant isolate, two ofloxacin-susceptible isolates were tested against all three fluoroquinolones using all four methods. RESULTS: Of the 797 M. tuberculosis isolates, 19 (2.4%) were ofloxacin-resistant by PM. MGIT 960 had 100% sensitivity (95% CI, 83%-100%) and specificity (95% CI, 99.5%-100%). Of the 797 isolates, 239 were from 2005 to 2006 and 6 of these (2.5%) were resistant by PM. MODS had 100% sensitivity (95% CI, 61%-100%) and specificity (95% CI, 98%-100%). NRA had 100% sensitivity (95% CI, 61%-100%) and 98.7% specificity (95% CI, 96%-99.6%). The median time to results was shorter using MGIT 960 (8 days), MODS (6 days) or NRA (9 days) compared with PM (21 days) (P < 0.001). All 19 ofloxacin-resistant isolates were resistant to ciprofloxacin, levofloxacin and moxifloxacin by PM. CONCLUSIONS: MGIT 960, MODS and NRA are sensitive and specific and more rapid than PM for identifying fluoroquinolone resistance in M. tuberculosis. Ofloxacin resistance was associated with cross-resistance to ciprofloxacin, levofloxacin and moxifloxacin.

Response to emerging infection leading to outbreak of linezolid-resistant enterococci.

Linezolid was approved in 2000 for treatment of gram-positive coccal infections. We performed a case-control study during a hospital outbreak of linezolid-resistant enterococci (LRE) infections, comparing cases of LRE infection (cases) with linezolid-sensitive enterococci infections (controls). Nasal and perirectal swab samples were obtained from all patients in a 1-day point-prevalence survey. We examined antimicrobial drug use and calculated the defined daily dose of linezolid per 1,000 patient-days. Fifteen LRE cases were identified (13 Enterococcus faecalis and 2 E. faecium); 7 were vancomycin-resistant. Compared with controls, case-patients had increased in-hospital mortality rates and lengths of stay. Multivariate analysis identified independent predictors of LRE infection: prior cultures positive for methicillin-resistant Staphylococcus aureus (adjusted odds ratio [AOR] 27), hospitalization duration before index culture (AOR 1.1 per day), and duration of preceding linezolid therapy (AOR 1.1 per day). Linezolid exposure and patient-to-patient transmission appear to be responsible for LRE infections, an important emeraina hospital problem.

Endemically acquired foodborne outbreak of enterotoxin-producing Escherichia coli serotype O169:H41.

PURPOSE: Enterotoxigenic Escherichia coli (ETEC) is traditionally recognized as a common cause of traveler's diarrhea, but is becoming a more frequent cause of foodborne disease outbreaks in the United States. It is important for public health practitioners and clinicians to be aware of ETEC as a domestic cause of gastroenteritis. We investigated a foodborne disease outbreak to understand the epidemiology of ETEC in this setting. METHODS: We conducted a cohort study of 63 employees of Company A. A case was defined as an employee who experienced diarrhea or vomiting or fever and cramps after eating a catered meal at Company A from August 14th-15th. A standardized questionnaire was administered to cases and controls. RESULTS: Of 63 employees, 36 met the case definition (Attack Rate = 57.1%). Diarrhea (94%) and cramps (74%) were common, whereas vomiting was not (3%). Mean duration of illness was 2.7 days. Coleslaw at the August 15th lunch was significantly associated with illness (Odds ratio = 4.4, 95% CI = 1.1-17). Stool specimens were positive for heat-stable enterotoxin-producing E. coli O169:H41. Contamination likely occurred at the point of service. CONCLUSIONS: This outbreak illustrates the changing epidemiology of enterotoxigenic E. coli and the importance for healthcare practitioners to consider ETEC as a potential cause of domestically acquired gastroenteritis.

Two community hepatitis B outbreaks: an argument for vaccinating incarcerated persons.

Current recommendations have not resulted in routine vaccination of correctional facility inmates for hepatitis B. We investigated two hepatitis B outbreaks. Outbreak 1 involved 4 cases epidemiologically linked to persons who had been in jail. Outbreak 2 involved 48 community cases; 69% had a history of incarceration. Two-thirds of the cases in these outbreaks might have been prevented by a program of routine vaccination of local jail inmates. Priority should be given to developing and supporting practical programs to vaccinate the high-risk populations in correctional facilities against hepatitis B.

Antimicrobial use and outcomes in patients with multidrug-resistant and pansusceptible Salmonella Newport infections, 2002-2003.

Multidrug-resistant Salmonella Newport with decreased susceptibility to ceftriaxone (MDR-AmpC) is becoming increasingly common in its food animal reservoirs and in humans. Few data exist on rates of antimicrobial use or differences in clinical outcomes in persons infected with MDR-AmpC or other Salmonella strains. We conducted a case-comparison analysis of data from a multistate population-based case-control study to identify antimicrobial treatment choices and differences in clinical outcomes in those infected with MDRAmpC compared to pansusceptible S. Newport. Of isolates from 215 laboratory-confirmed S. Newport cases, 54 (25%) were MDR-AmpC, 146 (68%) were pansusceptible, and 15 (7%) had other resistance patterns; 146 (68%) patients with S. Newport were treated with antimicrobial agents and 66 (33%) were hospitalized. Over two-thirds of cases at low-risk for serious complications received antimicrobial therapy, most commonly with fluoroquinolones, to which this strain was susceptible. There were no significant differences in symptoms, hospitalization, duration of illness, or other outcomes between the persons infected with MDR-AmpC and pansusceptible S. Newport. Although currently prevalent MDR-AmpC S. Newport strains remains susceptible to the antimicrobial most commonly prescribed for it, continued efforts to reduce unnecessary use of antimicrobial agents in food animals and humans are critical to prevent further development of resistance to quinolones and cephalosporins, which is likely to lead to substantial adverse outcomes.