Safety and efficacy of outpatient parenteral antibiotic therapy in an academic infectious disease clinic.

WHAT IS KNOWN AND OBJECTIVE: Outpatient parenteral therapy (OPAT) has become a safe and effective modality for patients requiring intravenous or prolonged antimicrobial therapy since the 1970s. It is being increasingly utilized in various settings; however, studies evaluating the safety and efficacy of clinic-based OPAT are limited. Since 2012, patients being considered for OPAT have required an infectious disease (ID) consultation at our institution. Candidates receiving once-daily antimicrobials who were ineligible for home infusion or nursing home placement as determined by their insurance companies and those who preferred the clinic over nursing home or home infusion were referred to the ID clinic. This study assessed the safety and outcome of patients receiving OPAT in an academic inner-city ID clinic in Detroit, Michigan. METHODS: This was a retrospective cross-sectional study of electronic medical records of patients, identified through clinic records, who received at least 2 days of OPAT from December 2012 to December 2015. Demographics, types of infections, antimicrobial regimen used, adverse events and outcome were evaluated. RESULTS: A total of 122 cases were identified during the study period. Mean age was 62 years with 55% male; 102 (84%) of 122 patients had peripherally inserted central catheter (PICC). Fifty-five per cent of patients participated in the clinic-based OPAT programme for insurance reasons, and 43% preferred the clinic over nursing home or home infusion. The most common infections were bone and joint (36%), followed by skin and soft tissue (18%) and urinary tract infections (12%). Ertapenem (44%) and daptomycin (41%) alone or in combination were used most frequently with 40% of patients receiving at least 4 weeks of treatment. Thirteen patients (11%) experienced one or more adverse drug events on daptomycin and/or ertapenem; of these, nine (69%) patients were receiving daptomycin monotherapy. Gastrointestinal symptoms (29%), cramping and myalgias (29%) and asymptomatic creatine phosphokinase (CPK) elevation (24%) were the most common adverse events. Three (3%) of 102 patients had PICC-related complications. Fourteen (88%) of 16 patients with adverse events or PICC-related complications required changing or stopping antibiotics; two (2%) had infection-related readmission. Conversely, 113 (93%) of 122 patients who completed treatment were considered cured and none had treatment failure at the end of 30 days of treatment. No patients died as a result of treatment or infection-related complications. WHAT IS NEW AND CONCLUSION: Outpatient parenteral therapy in our academic ID clinic was a safe and effective alternative to home infusion or skilled nursing facilities for patients requiring long-term antibiotics with few adverse events and complications.

Streptococcus equi subsp. zooepidemicus meningitis.

A 72-year-old woman was hospitalized for Streptococcus equi subsp. zooepidemicus meningitis. The same organism was cultured from her two horses. She denied contact with horses, but had a practice of consuming unpasteurized milk from a cow. The cow was in the same stable as the horses, and the ill woman's son milked the cow.

Infective endocarditis caused by USA300 methicillin-resistant Staphylococcus aureus (MRSA).

We report seven cases of infective endocarditis caused by USA300 methicillin-resistant Staphylococcus aureus (MRSA) at an urban, tertiary care, academic institution. Five strains were community associated and two were healthcare associated. All patients were injection drug users. Staphylococcus aureus isolates were characterised as USA300-type MRSA using pulsed-field gel electrophoresis. Five cases were right-sided endocarditis and two cases were left-sided. The mean length of in-hospital antimicrobial therapy was 23 days and the mean length of total antibiotic therapy was 55 days. Complications included heart failure resulting in valve replacement in one patient as well as death in that patient. As USA300 strains of MRSA continue to increase in prevalence, clinicians must be aware of the increasing spectrum of illness in considering management and prevention strategies.

High-level aminoglycoside-resistant enterococci. Colonization of nursing home and acute care hospital patients.

Enterococci with high-level resistance (HLR) to gentamicin sulfate and other aminoglycosides have emerged as pathogens in recent years. More than half of all current isolates of enterococci at the Ann Arbor (Mich) Veterans Administration (VA) Medical Center are HLR strains. We determined the rate of colonization with HLR enterococci in patients in the acute care hospital, the attached nursing home, and a private nursing home. We also studied the factors related to colonization and the molecular relatedness of strains of HLR enterococci in these settings. In the VA facilities, 47.4% of patients in the nursing home and 36.1% of patients in the acute care hospital were colonized, compared with a 4.3% colonization rate in the private nursing home. Intravenous or Foley catheters and bedridden status were associated with colonization in the acute care setting; the need for advanced nursing care and prior antibiotic therapy were associated with colonization in the nursing home. Environmental surfaces were contaminated with HLR enterococci in both VA settings. Plasmid analysis of HLR strains revealed identity between both patient and environmental strains in the nursing home care unit and the acute care hospital. Nursing home patients, with their high rate of colonization with HLR enterococci and their frequent movement into the acute care hospital, may play a role as a reservoir for subsequent transmission of HLR enterococci.

Nosocomial acquisition of Candida parapsilosis: an epidemiologic study.

OBJECTIVE: The purpose of this study was to determine aspects of the epidemiology of nosocomial infection due to Candida parapsilosis. Candida species are important nosocomial pathogens; however, little epidemiologic information is available. PATIENTS AND METHODS: We prospectively cultured specimens from 98 patients admitted to the bone marrow transplant unit and a medicine intensive care unit (ICU) of a tertiary care hospital. Specimens from hands of personnel and environmental surfaces were also cultured. Environmental cultures were done before patients were admitted to a studied unit. Restriction enzyme analysis (REA) of chromosomal DNA was used as a typing system to determine the relatedness of strains. RESULTS: C. parapsilosis was identified from five patients, six hand cultures from four hospital staff, and two environmental surfaces. All five patients had negative initial cultures and acquired C. parapsilosis after admission to the study unit. There were no significant differences between patients and control subjects in age, underlying disease, immunosuppressive therapy, and instrumentation. The duration of antibiotic therapy (median: 32.8 versus 11.8 days, p = 0.05) and the duration in the unit (means: 30.1 versus 16.1 days, p = 0.048) was longer in patients than in controls. No common source was identified. REA revealed three strain types; however, one strain type was identical in four patients, three staff members, and two environmental surfaces. CONCLUSION: These results suggest exogenous acquisition of C. parapsilosis. Based upon isolation of identical patient strains of C. parapsilosis from inanimate surfaces before patients were admitted to a study unit, there is evidence that the organism may have been acquired from the hospital environment. The principal mechanism of transmission was probably indirect contact via the hands of hospital personnel.

Association of contaminated gloves with transmission of Acinetobacter calcoaceticus var. anitratus in an intensive care unit.

PURPOSE: Acinetobacter calcoaceticus var. anitratus is an important nosocomial pathogen that has been associated with environmental reservoirs. An increased isolation rate of A. anitratus in our intensive care units (ICUs), from 0.03% (two of 7,800) to 0.5% (seven of 1,300) (p less than 0.00003), prompted an investigation. PATIENTS, METHODS, AND RESULTS: Ten patients were admitted to the surgical ICU and nine to the medical ICU during the outbreak period (late December 1987 to January 1988). Controls were all patients on the units who were not infected or colonized with the transmitted strain of A. anitratus. Three patients had A. anitratus pneumonia. A throat culture prevalence survey demonstrated three patients colonized with A. anitratus. Cases were placed in a cohort and symptomatic cases treated. An epidemiologic investigation was conducted to identify reservoirs and modes of transmission. Latex gloves were being used for universal precautions without routine changing of gloves between patients. Environmental sources culture-positive for A. antitratus included a small volume medication nebulizer and gloves in use for patient care. Plasmid typing showed that plasmid profiles of isolates from two symptomatic patients, two colonized patients, the nebulizer, and the gloves were identical. Other A. anitratus ICU isolates had distinct plasmid profiles. All patients with the transmitted strain had been in the surgical ICU. The need for changing gloves between patients and contaminated body sites was reinforced. CONCLUSION: Gloves, used incorrectly for universal precautions, may potentially transmit A. anitratus.

Invasive Candida guilliermondii infection: in vitro susceptibility studies and molecular analysis.

Candida guilliermondii is rarely isolated from humans. We describe a case of disseminated C. guilliermondii with associated purulent pericarditis, despite high-dose amphotericin B (AmB), in a 19-year-old female with aplastic anemia who underwent BMT. In vitro susceptibility studies of the 13 clinical isolates, two control strains and one environmental isolate revealed a minimum inhibitory concentration (MIC) range of (0.19-1.56 micrograms/ml) for AmB and (1.25-10 micrograms/ml) for fluconazole. Pulsed-field gradient gel electrophoresis was performed to evaluate possible similarities between strains. This case is significant for several reasons, the high degree and prolonged duration of fungemia despite high-dose AmB and concomitant flucytosine, the change in in vitro susceptibility during therapy, the initial misidentification of the yeast isolate, and the invasiveness of the organism. The poor response to therapy may have been due to the severe and sustained neutropenia and the high MICs of C. guilliermondii to AmB.

Control of endemic glycopeptide-resistant enterococci.

OBJECTIVE: To evaluate the epidemiology of, and control measures for, vancomycin-resistant Enterococcus (VRE) in a renal unit. DESIGN: A 3-month, prospective, prevalence culture survey of patients on a 24-bed renal unit. SETTING: A 975-bed community teaching hospital. PATIENTS: Patients admitted to the renal unit over a 3-month period. Patients identified with VRE were each matched with four patients without VRE isolated over the study period. INTERVENTIONS/CONTROL MEASURES: Resistant-organism barrier precautions. To eradicate carriage of VRE, two patients with VRE stool colonization were treated with 5 days of oral doxycycline (100 mg twice per day) and rifampin (300 mg/day). RESULTS: Seven patients with VRE (8 isolates) were identified. Five isolates were Enterococcus faecium (vancomycin MIC = 16 to 256 micrograms/mL), two were Enterococcus faecalis (MICs = 16 and 124 micrograms/mL), and one was Enterococcus gallinarum (MIC = 8.0 micrograms/mL). Eradication of carriage with VRE was accomplished in two patients treated with doxycycline and rifampin. In the final 30 days of the culture survey and at 9 months, there were no further patients with VRE identified. CONCLUSIONS: Resistant-organism precautions and elimination of patient carriage may be useful measures for controlling the spread of low-prevalence endemic vancomycin-resistant Enterococcus.

Comparative in vitro activity of antiseptics and disinfectants versus clinical isolates of Candida species.

OBJECTIVE: To evaluate the in vitro activity of antiseptics and detergents against Candida. DESIGN: One strain each of Candida albicans, Candida tropicalis, Candida lusitaniae, Candida parapsilosis, Candida kefyr, Candida glabrata, and an American Type Culture Collection strain of Escherichia coli (control) were studied. Clinical isolates were obtained from patients in a bone marrow unit of a large tertiary hospital. Antiseptic and disinfectant agents studied were used in the hospital where isolates were identified for cleaning of inanimate surfaces or hand washing. In vitro susceptibility was determined using a broth macrodilution method with exposure times to antiseptic or disinfectant agent of 15 seconds to 4 minutes and concentrations of agents that ranged from undiluted to 1:10,000 dilution. SETTING: A 900-bed teaching hospital. RESULTS: Of disinfectants tested, Vestal and Sparquat inhibited growth of all species at dilutions of < or = 1:100 at all contact times for all species. Clorox showed inhibition of growth at 1:100 dilution after 30 seconds of contact time for all isolates. Of antiseptics studied, Hibiclens inhibited growth of all species except C tropicalis at dilutions of < or = 1:100 at all contact times and for C tropicalis after 60 seconds. Clinidine inhibited growth of all species at dilutions of < or = 1:100 at all contact times for all species with the exception of Cglabrata and C tropicalis, which grew at the undiluted concentration. Ultradex failed to demonstrate killing of any species for any dilutions tested. CONCLUSIONS: The results of this study show varying degrees of in vitro inhibition of growth by a variety of antiseptics and disinfectants against clinical isolates of Candida species from hospitalized patients.

Enterococcal infections: an increasing problem in hospitalized patients.

We studied 157 episodes of infection or colonization with enterococci in 122 patients over a six-month period. One hundred twelve episodes (71.3%) occurred in patients over age 60 years. The most common sites for isolation of enterococci were the urinary tract, and bone and soft tissue. Nosocomial acquisition of enterococci occurred in 74.7% of all infections, and an additional 21% of episodes occurred in patients who had been transferred from another hospital or were regularly seen in the clinic. The overall mortality was 19.6%; 71.4% of those with bacteremia died. Enterococci appear to be significant pathogens, especially in older men in veterans' acute care hospitals and nursing home care units.

Controlling vancomycin-resistant enterococci.

After controlling an epidemic of vanB-type vancomycin-resistant Enterococcus faecium (VRE), we contained a subsequent vanA E faecium outbreak by using prospective laboratory-based surveillance, placing patients with VRE in private rooms, requiring the use of both gowns and gloves by all personnel entering the patients' rooms, and conducting prevalence surveys of patients on affected wards.

Time-kill kinetic studies of ampicillin/sulbactam for beta-lactamase-producing enterococci.

beta-Lactamase-producing (Bla+) enterococci have now been reported from several geographic areas. Most of these strains also demonstrate high-level aminoglycoside resistance, making therapy of serious infections due to Bla+ enterococci difficult. Using time-kill kinetic studies, we evaluated the activity of ampicillin-sulbactam (Am/SB) against five clinical Bla+ Enterococcus faecalis isolates from three geographically distinct areas. Am at fourfold minimum inhibitory concentrations (MIC) concentrations did not achieve bactericidal activity as determined by time-kill kinetic studies. Am/SB achieved 99.9% reduction in growth at 24 hr at twofold MIC concentrations without an aminoglycoside in four of five strains. SB alone had little independent activity against any of the strains, but synergy of killing was achieved in all five strains with a combination of Am + SB. No synergy was shown in a Bla- control strain. Am/SB may be useful for serious infections due to Bla+ enterococci.

In vitro activity of sparfloxacin and clinafloxacin against multidrug-resistant enterococci.

We evaluated the in vitro susceptibility of 140 clinical enterococcal isolates to the quinolones sparfloxacin and clinafloxacin. Isolates included Enterococcus faecalis (107), Enterococcus faecium (29), Enterococcus raffinosus (3), and one Enterococcus gallinarum. There were 111 isolates that showed high-level [minimum inhibitory concentrations (MICs) > or = 2000 micrograms/ml] resistance to gentamicin and were resistant to high levels of all other aminoglycosides; five isolates produced beta-lactamase; 21 isolates were resistant (MIC > or = 16 micrograms/ml) to ampicillin and were not beta-lactamase producers; and 13 strains were resistant (MIC > or = 32 micrograms/ml) to vancomycin. Most strains were susceptible to low concentrations of sparfloxacin and clinafloxacin, with MIC90S of 0.6 microgram/ml and 0.5 micrograms/ml, respectively. There were no inoculum effects. Time-kill experiments were performed with 22 strains; using 2 x MIC at 24 h, a > or = 2 log10 reduction in growth was observed with sparfloxacin and clinafloxacin for 14 and 17 strains, respectively. Time-kill synergism experiments were performed with 15 strains lacking high-level aminoglycoside resistance. In vitro bacterial synergism with the combination of sparfloxacin or clinafloxacin with streptomycin or gentamicin was observed for five and 12 isolates, respectively. The bactericidal activity of sparfloxacin and clinafloxacin suggest that these antibiotics may prove useful for therapy of multidrug resistant enterococci.

Comparative in vitro activity of quinupristin/dalfopristin against multidrug resistant Enterococcus faecium.

The in vitro susceptibilities of 82 strains of vancomycin resistant Enterococcus faecium (VREF), (49 vanA and 33 vanB) from over 13 hospitals in Europe and United States were studied. The MIC for several antibiotics showed high levels of resistance to vancomycin, ampicillin, gentamicin, and imipenem. All VREF strains were highly susceptible to quinupristin/dalfopristin with a MIC 90% of 0.5 microgram/ml for both vanA and vanB phenotypes. Time-kill and synergy studies of VREF for quinupristin/dalfopristin alone and quinupristin/dalfopristin in combination with several antibiotics (ampicillin, gentamicin, ciprofloxacin, rifampin and novobiocin) did not show bactericidal activity. In induction experiments using SF6550, (VREF, a vanA strain), quinupristin/dalforpristin showed a delay in the expression of vancomycin resistance by 2.5 hours. The results of this study show quinupristin/dalfopristin to have excellent in vitro activity versus multiple resistant E. faecium.

In vitro susceptibility and molecular analysis of gentamicin-resistant enterococci.

Enterococci with gentamicin MICs of 256 to 1,024 micrograms/mL were evaluated for susceptibility to ampicillin plus gentamicin synergism. Sixteen of eighteen enterococcal isolates were not susceptible to synergistic killing by ampicillin plus gentamicin; 11 possessed aac(6')-aph(2"), and 4 possessed aph(2")-Ic. A gentamicin MIC of 512 or 1,024 micrograms/mL predicted lack of ampicillin/gentamicin synergism, but a gentamicin MIC of 256 micrograms/mL did not. For six enterococcal strains possessing the gentamicin-resistance gene aph(2")-Ic, ampicillin plus dibekacin, ampicillin plus netilmicin, and ampicillin plus amikacin produced synergistic killing in five, three, and two strains, respectively.

In-vitro activity of arbekacin alone and in combination with vancomycin against gentamicin- and methicillin-resistant Staphylococcus aureus.

In-vitro susceptibility studies were performed on 99 clinical Staphylococcus aureus isolates. A total of 68 of 73 methicillin-resistant S. aureus and 2 of 26 methicillin-susceptible S. aureus were gentamicin-resistant (gentamicin MIC range 16 to 1,024 microg/mL). All 70 gentamicin-resistant isolates contained the aac(6')-Ie-aph(2'')-Ia aminoglycoside resistance gene, and none possessed the aph(2'')-Ic or aph(2'')-Id aminoglycoside resistance genes. The arbekacin MIC for the 70 gentamicin-resistant isolates ranged from 0.25 to 4 microg/mL. The combination of arbekacin plus vancomycin produced synergistic killing against 12 of 13 gentamicin-resistant MRSA isolates. The combination of gentamicin plus vancomycin produced synergistic killing against 7 of the same 13 isolates. Arbekacin may prove useful when used in combination with vancomycin in treating infections caused by gentamicin-resistant MRSA.

Comparative in vitro and bactericidal activity of oxazolidinone antibiotics against multidrug-resistant enterococci.

Increasing resistance among enterococci poses a considerable therapeutic problem. In this study, we evaluated the comparative in vitro activity of two investigational oxazolidinone antibiotics, eperezolid and linezolid, versus clinical isolates of multidrug-resistant enterococci. One hundred isolates (16 Enterococcus faecalis, 69 E. faecium, 10 E. gallinarum, 2 E. casseliflavus, 1 E. avium, 1 E. hirae, and 1 E. raffinosus) evaluated were collected from diverse geographic areas in North America and Europe from 1991 to 1995. Eperezolid MIC50 and MIC90 were 1.0 microgram/mL and 2.0 micrograms/mL (1.0-2.0 micrograms/mL range). Linezolid MIC50 and MIC90 were 2.0 micrograms/mL and 2.0 micrograms/mL (0.5-2.0 micrograms/mL range), respectively. MICs were the same at 10(3) CFU/mL and 10(8) CFU/mL initial inoculum. In time-kill experiments using 10 strains and concentrations of 4 micrograms/mL, 8 micrograms/mL, and 16 micrograms/mL (achievable serum concentrations) of eperezolid and linezolid there was a 2 log10 reduction of growth for 2 of 10 isolates tested using eperezolid and a 1 log10 reduction for 50% of isolates with both agents. There was indifferent bactericidal killing when either oxazolidinone was combined with gentamicin, ampicillin, or streptomycin for isolates lacking these resistances. This study demonstrates these oxazolidinone agents to have excellent in vitro activity versus multidrug-resistant enterococci.

In-vitro synergistic activity of the combination of ampicillin and arbekacin against vancomycin-and high-level gentamicin-resistant Enterococcus faecium with the aph(2")-Id gene.

The combination of ampicillin plus arbekacin produced synergistic killing against 8 of 13 vancomycin-, ampicillin-, gentamicin-, and streptomycin-resistant Enterococcus faecium isolates that possess the high-level gentamicin resistance gene, aph(2")-Id. This combination may prove useful in treating infections caused by multiresistant enterococci.

DNA analysis in the study of fungal infections in the immunocompromised host.

Fungal infections, most of which are caused by the Candida species, are an increasing problem in the immunocompromised host. The clinical manifestations of Candida infections include disseminated candidiasis, oral and esophageal infections, focal hepatic infections, peritoneal urinary tract infections, and wound infections. DNA methods, which include pulse field electrophoresis and restriction enzyme analysis of genomic DNA, have been used to increase understanding of the epidemiology of these infections. These techniques have shown that most Candida infections are endogenous or acquired from one's own flora. Recent outbreaks have provided evidence for exogenous acquisition of some isolates. Better methods for differentiation of colonization versus infection and identifying infection in the absence of positive cultures are under investigation.

The epidemiology of pseudallescheriasis complicating transplantation: Nosocomial and community-acquired infection.

The epidemiology of two cases of pseudallescheriasis in organ transplant patients are described and the disease in that population is reviewed. Disseminated hospital-acquired infection occurred in a liver transplant recipient and was fatal despite therapy with miconazole. A heart transplant recipient developed localized disease following soil contamination of soft tissue trauma which was cured with surgical resection and miconazole therapy. Itraconazole showed in vitro activity against Pseudallescheria boydii and should be evaluated in pseudallescheriasis. P. boydii infections are important complications of transplantation and should be considered in the differential diagnosis of community-acquired as well as nosocomial fungal infections in this population.