Maury Mulligan - Academia.edu (original) (raw)

Papers by Maury Mulligan

Infection and immunity, 1995

The clonal relationships among 187 bloodstream isolates of Escherichia coli from 179 patients at ... more The clonal relationships among 187 bloodstream isolates of Escherichia coli from 179 patients at Boston, Mass., Long Beach, Calif., and Nairobi, Kenya, were determined by multilocus enzyme electrophoresis (MLEE), analysis of polymorphisms associated with the ribosomal operon (ribotyping), and serotyping. MLEE based on 20 enzymes resolved 101 electrophoretic types (ETs), forming five clusters; ribotyping resolved 56 distinct patterns concordant with the analysis by MLEE. The isolates at each study site formed a genetically diverse group and demonstrated similar clonal structures, with the same small subset of lineages accounting for the majority of isolates at each site. Moreover, two ribotypes accounted for approximately 30% of the isolates at each study site. One cluster contained the majority (65%) of isolates and, by direct comparison of the ETs and ribotypes of individual isolates, was genetically indistinguishable from the largest cluster for each of two other collections of E....

Following implementation of special measures to control a nosocomial outbreak of methicillin-resi... more Following implementation of special measures to control a nosocomial outbreak of methicillin-resistant Staphylococcus aureus (MRSA), we used immunoblot typing in conjunction with antimicrobial susceptibility testing to investigate the epidemiology of this event and to determine whether this outbreak represented the failure of infection control measures to limit the spread of previously endemic MRSA strains or the introduction of a new strain of MRSA. Isolates of MRSA recovered from hospitalized patients were initially categorized on the basis of antimicrobial susceptibility results. Organisms susceptible to ciprofloxacin and/or trimethoprim/sulfamethoxazole were recovered from patients at a relatively constant rate prior to December 1988 and were categorized as endemic isolates. Subsequently, there was an outbreak due to organisms resistant to both of these antibiotics; these were therefore categorized as outbreak isolates. Isolates were later characterized by immunoblot typing. Prior to this analysis, isolates were given code numbers so that clinical and epidemiologic data as well as resistance patterns were not known until this testing was complete. Between January 1986 and November 1988, an average of 3.9 patients per month acquired nosocomial MRSA in the Sepulveda Veterans Administration Medical Center. In contrast, from December 1988 to October 1989, 369 MRSA isolates were collected from 125 patients (an average of 11.4 patients per month). Prior to December 1988, all tested nosocomial isolates of MRSA were susceptible to ciprofloxacin and/or to trimethoprim/sulfamethoxazole. In contrast, the outbreak was due to spread of MRSA isolates resistant to these antibiotics. Immunoblot typing of 204 isolates from 98 individuals identified five distinct immunoblot types of which types B and C were by far the most common. Type B was highly associated with outbreak isolates, whereas type C was associated with endemic isolates (p less than 0.001). All sequential isolates from single patients that belonged to different susceptibility categories demonstrated discordant immunoblot types. In contrast, concordant immunoblot types were observed for 25 of 27 sequential isolates that displayed minor variations in antimicrobial resistance. The institution of more stringent infection control measures was followed by the return of nosocomial MRSA acquisition rates to pre-outbreak levels. Although novobiocin and trimethoprim/sulfamethoxazole were extensively used to treat patients harboring outbreak and endemic isolates, respectively, in no instance was the initial MRSA isolate from any patient resistant to novobiocin and only 6% of initial endemic isolates displayed trimethoprim/sulfamethoxazole resistance. A modest, significant increase in the resistance of endemic isolates to various other antimicrobial agents was noted however. Immunoblot analyses provided strong, corroborative evidence that at least two separate strains of MRSA were present during the outbreak and that a newly introduced strain with a distinctive antimicrobial resistance pattern was primarily responsible for the rapid spread of MRSA during the outbreak. The observation that previously effective infection control measures failed to prevent the nosocomial spread of a newly introduced community-acquired MRSA strain suggests that a single set of control measures may not be equally efficacious against all strains of MRSA. In this regard, previously reported variations in resistance to topical antimicrobials and/or antiseptics, and differences in virulence factors such as colonization potential, invasiveness, and survival on fomites, may warrant further study. Control of the outbreak strain of MRSA in our institution did occur after the implementation of more strenuous isolation procedures.(ABSTRACT TRUNCATED)

Journal of clinical microbiology, 1985

Clinical isolates of agar-pitting, formate-fumarate-requiring, anaerobic gram-negative bacilli we... more Clinical isolates of agar-pitting, formate-fumarate-requiring, anaerobic gram-negative bacilli were recharacterized in consideration of the species descriptions of Bacteroides ureolyticus and the newly described B. gracilis, Campylobacter concisus, and Wolinella sp. During an 11-year period, 7.5% (101 of 1,341) of all specimens yielding anaerobes were found to contain an organism in this group. Of the 71 isolates that were available for study, 43 were B. ureolyticus, 23 were B. gracilis, and 5 were in the Wolinella-C. concisus group. The role in infection and patterns of antimicrobial susceptibility for B. ureolyticus and B. gracilis were studied. Review of the clinical data indicated that 83% of B. gracilis strains were recovered from patients with serious visceral or head and neck infection, whereas 73% of B. ureolyticus isolates were recovered from superficial soft-tissue or bone infections. The strains of B. ureolyticus were uniformly susceptible to the tested antimicrobial agen...

Journal of Antimicrobial Chemotherapy, 1994

By using dot blot hybridization, 69 of 102 Clostridium difficile isolates (68%) from the United S... more By using dot blot hybridization, 69 of 102 Clostridium difficile isolates (68%) from the United States and other countries hybridized with at least one of nine DNA probes for erythromycin (Erm), tetracycline (Tet) or chloramphenicol (Cat) resistance determinants. The distribution of individual determinants in descending order of frequency was: Tet M, 32%; Erm Q, 25%; Erm FS, 18%; Tet P, 15%; Tet K, 15%; Cat P, 15%; Cat Q, 12%; Erm BP, 11%; Tet L, 7%. This is the first report of Tet P being carried by C. difficile and hitherto Erm FS has only been found within the genus Bacteriodes, while neither Tet K nor Tet L have been previously identified among the genus Clostridia. Eighteen percent of the hybridizing isolates carried multiple determinants coding for the same phenotype. A higher frequency of resistance genes was associated with prior exposure to antimicrobial agents, cytotoxin production and diarrhoea. Isolates recovered from bone marrow transplant patients carried significantly fewer antibiotic resistance genes than did those from immunocompetent general medicine patients. However, this may be due to the fact that each was located at a different site. Antibiotic resistance determinants may play a role in the virulence associated with C. difficile.

Infection Control and Hospital Epidemiology, 2001

To investigate an outbreak of Burkholderia cepacia. Observational study and chart review. Adult n... more To investigate an outbreak of Burkholderia cepacia. Observational study and chart review. Adult non-cystic fibrosis (CF) patients. Intensive care units (ICUs) at a university-affiliated teaching hospital. As part of the epidemiological investigation, we conducted a chart review and collected environmental samples. A review of work schedules of healthcare workers also was performed. We used B. cepacia selective agar for preliminary screening for all isolates, which subsequently were confirmed as members of the B. cepacia complex by polyphasic analysis employing conventional biochemical reactions and genus- and species-specific polymerase chain reaction assays. Pulsed-field gel electrophoresis, randomly amplified polymorphic DNA typing, and automated ribotyping were used to genotype the isolates. As part of the intervention, contact isolation precautions were initiated for all patients identified as having had a culture positive for B. cepacia. Between September 1997 and September 1999, B. cepacia was isolated from 31 adult patients without CF in ICUs at a university-affiliated teaching hospital. Based on geographic clustering and genotypic analysis, three distinct clusters were observed involving 20 patients. Isolates from 17 of these patients were available for testing and were found to be of the same strain (outbreak strain). Further taxonomic analysis indicated that the outbreak strain was B. cepacia complex genomovar III. Twelve (71%) of the 17 patients were judged to be infected, and 5 (29%) were colonized with this strain. Six of 200 environmental cultures from multiple sources in the hospital's ICUs yielded B. cepacia. Two of these isolates, both recovered from rooms of colonized patients, were the same genotype as the outbreak strain recovered from patients. Despite an extensive investigation, the source of the B. cepacia clone involved in this outbreak remains unknown. The spatial and temporal pattern of cases suggests that cross-transmission of a genetically related strain contributed to clustering among patients. The initiation of contact isolation may have limited the extent of this transmission. Additional studies are needed to elucidate better the epidemiology of nosocomial B. cepacia infection among non-CF adult patients.

Infection Control and Hospital Epidemiology, 1991

... discriminatory power for methicillin-susceptible S aureus) have only limited utility in analy... more ... discriminatory power for methicillin-susceptible S aureus) have only limited utility in analyzing ... have suggested that this technique may be appropriate for many clinical laboratories ... develop a reproducible classification of isolates, the investigators used an automated gel scanner ...

Infection Control and Hospital Epidemiology, 1996

Microbial strain typing is a useful adjunct to clinical epidemiology. Phenotypic typing systems e... more Microbial strain typing is a useful adjunct to clinical epidemiology. Phenotypic typing systems examine expressed characteristics, whereas genotypic systems, including recent PCR-based systems, examine chromosomal or plasmid DNA. Typing systems have evaluated bacteria, fungi, and viruses successfully. The criteria used to assess the utility of each system include typeability, reproducibility, and discriminatory power.

Infection Control and Hospital Epidemiology, 1995

American Journal of Medicine, 1993

Current Microbiology, 1979

Clostridium difficile was recovered from a variety of environmental sites in three hospital rooms... more Clostridium difficile was recovered from a variety of environmental sites in three hospital rooms occupied by a patient who had colitis due to this organism. C difficile was detected for 40 days after the patient was moved from one of these rooms, These findings suggest that the contaminated hospital environment may be a clinically significant reservoir for C. difficite and that this organism may be a nosocomial pathogen. Isolation of patients and adequate decontamination of rooms may be needed to minimize risk to other patients.

Annals of Emergency Medicine, 1981

A 64-year-old man presented with a history of four days of lower abdominal pain and 12 hours of c... more A 64-year-old man presented with a history of four days of lower abdominal pain and 12 hours of cutaneous discoloration, bullae formation, and swelling of the soft tissues of abdominal wall and right thigh. Myonecrosis of abdominal wall and an adenocarcinoma of the cecum were found at operation. Cultures of blood and fluid from the bullae yielded Clostridium septicum. Nontraumatic clostridial myonecrosis is a fulminant, usually fatal disease that is most often the result of bacteremia from an occult gastrointestinal lesion. Ulceration of the colon or terminal ileum is the most common predisposing condition, and is usually due to gastrointestinal or hematological malignancy. Patients often present with nonspecific complaints, including pain at the affected site and fever. The disease progresses rapidly to include bronze discoloration, edema, and hemorrhagic bullous lesions of the skin, subcutaneous emphysema, and myonecrosis. Presumptive diagnosis often can be made by Gram stain of the bullous fluid that reveals gram-positive bacilli and a paucity of leukocytes. Favorable outcome depends on prompt institution of appropriate antimicrobial therapy and surgical debridement of involved soft tissues, as well as correction of the underlying disorder. This disease should be considered to be a medical-surgical emergency.

Anesthesia & Analgesia, 1994

We prospectively studied the relationship of perioperative methicillin-resistant Staphylococcus a... more We prospectively studied the relationship of perioperative methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization and subsequent infection in surgical intensive care unit (SICU) patients. In addition, risk factors for MRSA nasal colonization were examined. All patients admitted to the 15-bed SICU between August 1991 and July 1992 had their anterior nares cultured. Cultures positive for S. aureus were subsequently placed on oxacillin-containing plates to screen for methicillin-resistance. Of 484 patients, 19 had MRSA nasal colonization (3.9%). There were five infections in the 19 patients with positive perioperative nasal cultures versus six infections in the remaining 465 patients (P < 0.0001). Immunoblot typing confirmed the concordance of colonizing and infecting strains. Prior exposure to the spinal cord injury center (P < 0.001) and prior antibiotic therapy (P < 0.003) were also significant multivariate risk factors for perioperative nasal colonization. Patients with perioperative MRSA nasal colonization are at significantly increased risk of subsequent postoperative MRSA infection.

American Journal of Transplantation, 2006

The 2005 American Society of Transplant Surgeons (ASTS) Winter Symposium entitled 'The Ar... more The 2005 American Society of Transplant Surgeons (ASTS) Winter Symposium entitled 'The Art and Science of Immunosuppression' explored ways to maximize existing immunosuppressive protocols and to develop new strategies incorporating novel agents and emerging diagnostic technologies to customize immunosuppression and reduce side effects. Several presentations evaluated steroid withdrawal or avoidance protocols reflecting the significant difficulties of bone loss, glucose control and growth retardation in children associated with long-term steroid use. Calcineurin-inhibitor related renal dysfunction of both native and transplanted kidneys was identified as significant, but no consensus was reached concerning effective prevention. Similarly, recurrence of Hepatitis C following liver transplantation was identified as problematic without identifying a preferred immunosuppressive regimen in this setting. Control of T-cell mediated rejection was found to be excellent, but recognition and treatment of non-T cell causes of allograft damage (i.e. B- or NK-cell mediated) was identified as an area of current interest. Immunosuppressive agents under development, such as those blocking co-stimulation or cytokine signals, and JAK-3 inhibitors were discussed. Finally, the available technologies for molecular and genetic diagnostics and the clinical correlation in the post-transplant setting were discussed.

The American Journal of Medicine, 1992

The American Journal of Medicine, 1985

The efficacy and safety of ticarcillin plus clavulanic acid in the treatment of patients with inf... more The efficacy and safety of ticarcillin plus clavulanic acid in the treatment of patients with infections of soft tissue, bone, and joint were evaluated in this open study. Clinical diagnoses included osteomyelitis, soft tissue abscess or ulcer, cellulitis, bite wound, traumatic or postoperative cellulitis, necrotizing fasciitis, septic arthritis, septic bursitis, and septic thrombophlebitis. Trauma or underlying disease such as diabetes mellitus or vascular insufficiency was common (more than 50 percent) in the patient population. Clinical efficacy was evaluable in 66 patients who received 3 g of ticarcillin and 0.1 g of clavulanic acid every four or six hours for a mean of 23.4 days. A satisfactory clinical response was observed in 92 percent of the patients. Major pathogens isolated were Enterobacteriaceae, anaerobic cocci, Staphylococcus aureus, and beta-hemolytic Streptococcus. Of the 143 isolates recovered from 55 bacteriologically evaluable cases, 87 percent were eradicated by therapy. Overall, a satisfactory bacteriologic outcome occurred in 93 percent of the patients, and the pathogen(s) persisted in 7 percent. More than 98 percent of the isolates were susceptible to ticarcillin plus clavulanic acid in vitro. Emergence of resistance during therapy occurred with three strains of Pseudomonas aeruginosa. Adverse drug-related reactions required discontinuation of treatment in two patients, although other minor abnormal laboratory findings were common. These results indicate that ticarcillin plus clavulanic acid offers safe and effective therapy for infections of soft tissue, bone, and joint.

American Journal of Infection Control, 1990

We studied the acquisition and transmission of Clostridium difficile infection prospectively on a... more We studied the acquisition and transmission of Clostridium difficile infection prospectively on a general medical ward by serially culturing rectal-swab specimens from 428 patients admitted over an 11-month period. Immunoblot typing was used to differentiate individual strains of C. difficile. Seven percent of the patients (29) had positive cultures at admission. Eighty-three (21 percent) of the 399 patients with negative cultures acquired C. difficile during their hospitalizations. Of these patients, 52 (63 percent) remained asymptomatic and 31 (37 percent) had diarrhea; none had colitis. Patient-to-patient transmission of C. difficile was evidenced by time-space clustering of incident cases with identical immunoblot types and by significantly more frequent and earlier acquisition of C. difficile among patients exposed to roommates with positive cultures. Of the hospital personnel caring for patients with positive cultures, 59 percent (20) had positive cultures for C. difficile from their hands. The hospital rooms occupied by symptomatic patients (49 percent) as well as those occupied by asymptomatic patients (29 percent) were frequently contaminated. Eighty-two percent of the infected cohort still had positive cultures at hospital discharge, and such patients were significantly more likely to be discharged to a long-term care facility. We conclude that nosocomial C. difficile infection, which was associated with diarrhea in about one third of cases, is frequently transmitted among hospitalized patients and that the organism is often present on the hands of hospital personnel caring for such patients. Effective preventive measures are needed to reduce nosocomial acquisition of C. difficile.

American Journal of Infection Control, 1999

Clostridium difficile disease (CDD) is a common nosocomially acquired intestinal disease, and app... more Clostridium difficile disease (CDD) is a common nosocomially acquired intestinal disease, and approximately 20% of patients have recurrent episodes of CDD. Risk factors for CDD include hospitalization, older age, multiple medical problems, and antibiotic exposure. We identified 5 women who did not have the typical risk factor profile during a multicentered clinical trial testing a new combination treatment (Saccharomyces boulardii, Laboratories Biocodex, Montrouge, France and standard antibiotics) for patients with active recurrent CDD. These 5 women were young, otherwise healthy, and were not hospitalized at the time of their first episode, but all had given birth just before their first episode of CDD.