Vancomycin MIC susceptibility testing of methicillin-susceptible and methicillin-resistant Staphylococcus aureus isolates: a comparison between Etest® and an automated testing method.

BACKGROUND: Vancomycin treatment failures and increased mortality have been reported in methicillin-resistant Staphylococcus aureus (MRSA) isolates with minimum inhibitory concentrations (MICs) >1 µg/mL. Most of this data utilized manual testing to determine the MIC. Recent vancomycin treatment guidelines do not specify the optimal testing method to define the MIC. METHODS: Over a twelve-month study period, we compared manual susceptibility testing by Etest® (AB Biodisk, Solna, Sweden) with automated testing by MicroScan Walk-Away® (Dade Behring, Inc., East Mississauga, Ontario) to determine the difference in the MICs among 383 sequential clinical S aureus isolates. RESULTS: Manual testing demonstrated MICs of 1.5 µg/mL or 2.0 µg/mL in 90% and 86% of MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) isolates, respectively. Automated testing revealed MICs of 2.0 µg/mL for 56% and 54% of MRSA and MSSA isolates, respectively. The manual MIC test by Etest® was >1 µg/mL in 87% of MRSA isolates and 86% of methicillin-susceptible S aureus isolates in which the automated MIC result was 1 µg/mL. This same finding occurred in 94% (17/18) of S aureus isolates causing non-skin/skin structure infections. Among all subgroups of isolates, manual testing demonstrated statistically significant higher MICs compared to automated testing. CONCLUSIONS: MIC results generated by the Etest® consistently revealed a one dilution higher vancomycin MIC compared to MicroScan®. Automated MIC results of invasive MRSA isolates should be confirmed by manual Etest® to ensure identification of those isolates with vancomycin MICs >1µg/mL that are at risk for vancomycin treatment failure or increased mortality.

Targeted intranasal mupirocin to prevent colonization and infection by community-associated methicillin-resistant Staphylococcus aureus strains in soldiers: a cluster randomized controlled trial.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen that primarily manifests as uncomplicated skin and soft tissue infections. We conducted a cluster randomized, double-blind, placebo-controlled trial to determine whether targeted intranasal mupirocin therapy in CA-MRSA-colonized soldiers could prevent infection in the treated individual and prevent new colonization and infection within their study groups. We screened 3,447 soldiers comprising 14 training classes for CA-MRSA colonization from January to December 2005. Each training class was randomized to either the mupirocin or placebo study group, and the participants identified as CA-MRSA colonized were treated with either mupirocin or placebo. All participants underwent repeat screening after 8 to 10 weeks and were monitored for 16 weeks for development of infection. Of 3,447 participants screened, 134 (3.9%) were initially colonized with CA-MRSA. Five of 65 (7.7%; 95% confidence interval [95% CI], 4.0% to 11.4%) placebo-treated participants and 7 of 66 (10.6%; 95% CI, 7.9% to 13.3%) mupirocin-treated participants developed infections; the difference in the infection rate of the placebo- and mupirocin-treated groups was -2.9% (95% CI, -7.5% to 1.7%). Of those not initially colonized with CA-MRSA, 63 of 1,459 (4.3%; 95% CI, 2.7% to 5.9%) of the placebo group and 56 of 1,607 (3.5%; 95% CI, 2.6% to 5.2%) of the mupirocin group developed infections; the difference in the infection rate of the placebo and mupirocin groups was 0.8% (95% CI, -1.0% to 2.7%). Of 3,447 participants, 3,066 (89%) were available for the second sampling and completed follow-up. New CA-MRSA colonization occurred in 24 of 1,459 (1.6%; 95% CI, 0.05% to 2.8%) of the placebo group participants and 23 of 1,607 (1.4%; 95% CI, 0.05% to 2.3%) of the mupirocin group participants; the difference in the infection rate of the placebo and mupirocin groups was 0.2% (95% CI, -1.3% to 1.7%). Despite CA-MRSA eradication in colonized participants, this study showed no decrease in infections in either the mupirocin-treated individuals or within their study group. Furthermore, CA-MRSA eradication did not prevent new colonization within the study group.

Multidrug-resistant Acinetobacter extremity infections in soldiers.

War wound infection and osteomyelitis caused by multidrug-resistant (MDR) Acinetobacter species have been prevalent during the 2003-2005 military operations in Iraq. Twenty-three soldiers wounded in Iraq and subsequently admitted to our facility from March 2003 to May 2004 had wound cultures positive for Acinetobacter calcoaceticus-baumannii complex. Eighteen had osteomyelitis, 2 burn infection, and 3 deep wound infection. Primary therapy for these infections was directed antimicrobial agents for an average of 6 weeks. All soldiers initially improved, regardless of the specific type of therapy. Patients were followed up to 23 months after completing therapy, and none had recurrent infection with Acinetobacter species. Despite the drug resistance that infecting organisms demonstrated in this series, a regimen of carefully selected extended antimicrobial-drug therapy appears effective for osteomyelitis caused by MDR Acinetobacter spp.

Induction of telithromycin resistance by erythromycin in isolates of macrolide-resistant Staphylococcus spp.

Staphylococcal isolates were examined for possible macrolide-inducible resistance to telithromycin. All macrolide-resistant isolates demonstrated telithromycin D-shaped zones. This result did not discriminate between resistance due to an efflux mechanism (msrA) or a ribosomal target modification (ermA or ermC). Inducible telithromycin resistance in staphylococci does not appear to be analogous to inducible clindamycin resistance.

Methicillin-resistant Staphylococcus aureus (MRSA) nares colonization at hospital admission and its effect on subsequent MRSA infection.

BACKGROUND: Asymptomatic colonization with methicillin-resistant Staphylococcus aureus (MRSA) has been described as a risk factor for subsequent MRSA infection. MRSA is an important nosocomial pathogen but has currently been reported in patients without typical risk factors for nosocomial acquisition. This study was designed to evaluate the impact of asymptomatic nares MRSA colonization on the development of subsequent MRSA infection. The incidence of MRSA infection was examined in patients with and patients without MRSA or methicillin-susceptible S. aureus (MSSA) colonization at admission to the hospital and in those who developed colonization during hospitalization. METHODS: Patients admitted to 5 representative hospital units were prospectively evaluated. Nares samples were obtained for culture at admission and during hospitalization. Laboratory culture results were monitored to identify all MRSA infections that occurred during the study period and 1 year thereafter. RESULTS: Of the 758 patients who had cultures of nares samples performed at admission, 3.4% were colonized with MRSA, and 21% were colonized with MSSA. A total of 19% of patients with MRSA colonization at admission and 25% who acquired MRSA colonization during hospitalization developed infection with MRSA, compared with 1.5% and 2.0% of patients colonized with MSSA (P<.01) and uncolonized (P<.01), respectively, at admission. MRSA colonization at admission increased the risk of subsequent MRSA infection, compared with MSSA colonization (relative risk [RR], 13; 95% confidence interval [CI], 2.7-64) or no staphylococcal colonization (RR, 9.5; 95% CI, 3.6-25) at admission. Acquisition of MRSA colonization also increased the risk for subsequent MRSA infection, compared with no acquisition (RR, 12; 95% CI, 4.0-38). CONCLUSION: MRSA colonization of nares, either present at admission to the hospital or acquired during hospitalization, increases the risk for MRSA infection. Identifying MRSA colonization at admission could target a high-risk population that may benefit from interventions to decrease the risk for subsequent MRSA infection.

The effect of semipermeable dressings on smallpox vaccine site evolution.

BACKGROUND: Many hospital systems in the United States are contemplating the implementation of a smallpox vaccination program. The Centers for Disease Control and Prevention and other organizations recommend use of occlusive dressings over the vaccination site of health care workers in contact with patients. Minimal data are available on the impact of an occlusive dressing on the evolution of the vaccinia inoculation site. METHODS: We conducted a prospective observational study in which subjects were instructed to cover their vaccination site with either a semipermeable dressing over gauze or gauze alone. We recorded the duration of semipermeable dressing use and parameters pertaining to vaccination site evolution, to include time until scab separation. RESULTS: The increased use of a semipermeable dressing is associated with increased time until scab separation (n = 41, r =.48, P =.001 by regression analysis). This analysis predicts a 9-day difference in time until scab separation between patients that wore semipermeable dressings 100% of the time versus not at all. No significant correlation was observed between semipermeable dressing use and size of maximum erythema, time until maximum erythema, size of erythema on day 6 or 8, nor time until pustule formation. CONCLUSION: Semipermeable dressing use appears to prolong the time until scab separation and possibly the duration of infectivity and risk of secondary transmission. Health care organizations may wish to consider this information when instituting a smallpox vaccination program.

Frequency of vaccinia virus isolation on semipermeable versus nonocclusive dressings covering smallpox vaccination sites in hospital personnel.

BACKGROUND: The Centers for Disease Control and Prevention recommends a semipermeable occlusive dressing for hospital workers who receive smallpox vaccination. OBJECTIVE: The study was designed to determine the frequency of vaccinia virus isolation from the outer surface of semipermeable dressings and to compare the prevalence of vaccinia virus on the outer surface of semipermeable dressings with its prevalence on the outer surface of nonocclusive dressings. METHODS: A prospective, observational study was conducted on hospital employees who received smallpox vaccination at a military academic medical center. Subjects were instructed to wear a semipermeable dressing if they had direct patient contact. Employees without direct patient care had the option of wearing a semipermeable dressing or a nonocclusive dressing. Prior to a programmed dressing change, the outer surface of the bandage site was swabbed and cultured for virus. Samples were considered positive when cytopathic effects were observed, with results confirmed as vaccinia by polymerase chain reaction. RESULTS: A total of 212 cultures were obtained from 93 subjects. All cultures directly obtained from active lesions were positive (13/13). Positive cultures were obtained from 7% (10/135) of the semipermeable dressings and 23% (15/64) of the nonocclusive dressings (P <.05). Ten percent (8/79) of the semipermeable dressings with purulent exudate observed underneath the bandage were culture positive, compared with 4% (2/56) of semipermeable dressings with no purulent exudate observed underneath the bandage (P=.19). CONCLUSIONS: Compared with nonocclusive dressings, the semipermeable dressing reduced, but did not eliminate, the frequency with which vaccinia virus was cultured from the surface of the dressing. Virus was present, but only rarely, on the dressing surface in the absence of purulent exudate under the semipermeable dressings.

Successful desensitization to high-dose methotrexate after systemic anaphylaxis.

BACKGROUND: Methotrexate (MTX) is a folic acid antagonist used in high doses as adjuvant chemotherapy for osteosarcoma. It has many known toxicities and has been reported to cause anaphylaxis. We report the first successful desensitization protocol to high-dose MTX. CASE PRESENTATION: The patient is a 22-year-old male with the evaluation of osteosarcoma, T1Gr2NxM0. He received neoadjuvant chemotherapy and later underwent a right above the knee amputation without complication. He was then scheduled to receive adjuvant chemotherapy with high-dose MTX, 12 g/m2 body surface area, followed by leucovorin rescue and ifosfamide. He had an immediate hypersensitivity reaction during the initiation of the MTX infusion with diffuse urticaria, facial swelling, cough, and chest tightness. The infusion was terminated and his symptoms abated. He was later skin tested to confirm allergy to MTX. In order for him to receive the needed chemotherapy, we developed a desensitization protocol that was administered in the intensive care unit. Before the infusion he was pretreated with ranitidine, cetirizine, hydroxyzine, montelukast, and prednisone. He underwent the desensitization without incident on repeated infusions. Serum tryptase levels drawn during the infusions were low, signifying controlled mast cell degranulation. CONCLUSIONS: This case describes the original development of a desensitization protocol to high-dose MTX. The successful development and implementation of this protocol will have impact on patients who have anaphylactic reactions to MTX but require this medication for specific diseases. For patients who suffer from osteogenic sarcoma and have anaphylactic reactions to MTX, this desensitization protocol will allow these patients to continue with needed therapeutic or palliative chemotherapy.

Disseminated Histoplasmosis Mimicking Felty's Syndrome.

The successful treatment of rheumatoid arthritis often requires the use of immunosuppressive medications. Although these agents have different potential toxicities, they share in common the potential for permitting the development of opportunistic infections. We describe 2 patients with chronic rheumatoid arthritis treated with immunosuppressive agents who developed progressive neutropenia with documented splenomegaly. The differential diagnosis included Felty's syndrome versus bone marrow suppression from their immunosuppressive medication. Although both patients had the triad of Felty's syndrome, high titer seropositive rheumatoid arthritis with splenomegaly and neutropenia, the diagnosis of this syndrome relies on excluding other potential causative factors. Further investigation revealed that both patients had disseminated histoplasmosis with bone marrow involvement, which most likely represented reactivation from prior exposure to Histoplasma capsulatum. Opportunistic infections such as disseminated histoplasmosis can mimic other disease processes, including Felty's syndrome, and are important to consider when there is a change in the clinical status of patients with rheumatic disease who are immunocompromised.