How (and why) to set up a facilitywide TB program.
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Biomedical subjects
Publications and source records attributed to R A Weinstein.
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Breast abscesses in nonlactating women are very uncommon. Rarely have cases been reported in which coagulase-negative staphylococci have been isolated in pure culture. We describe a 67-year-old patient who had such an abscess. Specimens obtained by fine needle aspiration, incision and drainage, and biopsy of the breast mass all showed acute inflammation and many gram-positive cocci on gram stain and histologic examination; cultures of all specimens yielded many coagulase-negative staphylococci. The patient responded well to incision and drainage and therapy with antibiotics.
Ceftazidime-resistant isolates of Escherichia coli and Klebsiella pneumoniae produced a plasmid-mediated beta-lactamase with a pI of 5.6 with biochemical characteristics comparable to those of the TEM-10 beta-lactamase. Plasmids from the two strains were nonidentical. Both TEM-10 sequences differed from TEM-1 by substitutions of Ser-162 and Lys-237. The nucleotide sequences of the two genes were identical except for three silent nucleotide substitutions corresponding to the nucleotide differences in the Tn2 TEM-1 or Tn3 TEM-1 genes. The original TEM-10 plasmid was identical to that found in the E. coli isolate and coded for a gene that corresponded to the TEM-10 beta-lactamase from Tn2.
OBJECTIVE: To measure in-vitro antiviral drug susceptibilities of human immunodeficiency virus type 1 (HIV-1) isolates recovered from patients treated with alpha-interferon or zidovudine and patients not treated with these drugs and to examine the relation of these susceptibility measurements to duration of therapy, disease stage, and response to alpha-interferon therapy. DESIGN: Cross-sectional study. SETTING: Outpatient HIV clinic. PATIENTS: Twenty-six ambulatory HIV-1-infected patients: Fifteen of these patients were receiving alpha-interferon therapy, and 11 had never received such therapy. Nine patients were participating in a clinical trial of combination therapy with zidovudine and alpha-interferon. MEASUREMENTS: The 50% inhibitory concentration (IC50) of zidovudine and alpha-interferon was determined for HIV-1 isolates recovered from each patient. Plasma concentrations of HIV-1 p24 antigen in the nine patients in the clinical trial were measured monthly after alpha-interferon was added to zidovudine monotherapy. RESULTS: Zidovudine IC50 (range, 0.01 to 4.87 microM) increased steadily with duration of zidovudine therapy (r = 0.57, P = 0.003). In contrast, alpha-interferon IC50 (range, 0.8 to 415 units/mL) was not related to duration of alpha-interferon treatment; in fact, high IC50s were found in isolates from patients who had never received exogenous alpha-interferon therapy. Resistance to alpha-interferon was greater in isolates from the 15 patients with the acquired immunodeficiency syndrome (AIDS) (median, 104 units/mL) than in those from the 10 patients without AIDS (median, 50 units/mL). Interferson activity was detected in plasma samples from 23 of 24 patients and was also at higher levels in patients with AIDS than in HIV-infected patients without AIDS. Reductions in plasma concentrations of HIV-1 p24 antigen in nine patients after beginning alpha-interferon therapy were greater in those with more susceptible isolates (r = -0.72, P = 0.03). CONCLUSIONS: Interferon resistance, possibly due to endogenous interferon, is not related to duration of interferon therapy but may limit the effectiveness of interferon therapy. Determinations of interferon susceptibility may identify patients most likely to benefit from this agent.
In an open-label dose-ranging pilot trial, 13 homosexual men with human immunodeficiency virus type 1 (HIV-1) p24 antigenemia after at least 6 weeks of zidovudine monotherapy were continued on zidovudine and given interferon-alpha, 1.25-7.5 x 10(6) units/m2 subcutaneously three times/week. Plasma p24 antigen levels demonstrated a biphasic response, falling initially in 11 patients by a mean of 50% (95% confidence interval, 36%-64%; P = .001) at a median of 11 weeks, but rising steadily thereafter (P = .001). CD4+ cell counts fell by a mean of 7.1 cells/mm3/week (P = .01). Higher initial CD4+ counts predicted greater p24 antigen reductions. At higher interferon doses no greater reductions in p24 antigen occurred, but side effects were more severe and CD4+ lymphocyte counts fell faster. Polymerase chain reaction quantification of HIV-1 DNA in 3 patients showed a biphasic pattern paralleling the p24 antigen response. In sum, although evidence of short-term effects was found, the combination showed no evidence of lasting antiviral activity beyond that achieved with zidovudine alone in patients with advanced HIV-1 infection.
Traditional infection control measures in intensive care units (ICUs) have been directed at limiting person to person spread of infection and improving care of invasive devices. These measures often fail because they have little effect on patients' endogenous flora, which is an important source of infection in ICUs. Improvements in the design and aseptic care of invasive devices have helped to decrease the risk of progression from colonization to infection in individual patients. Interest is growing also in use of selective decontamination to decrease ICU infection rates. Despite these advances, basic hygiene and appropriate, prospectively monitored use of antibiotics remain essential components of ICU care.
Conventional infection control measures in intensive care units (ICUs) are aimed primarily at stemming cross-infections. The role of patients' endogenous flora in the pathogenesis of nosocomial infection and occasional lapses in aseptic technique in ICUs help to explain the frequent failure of the conventional approaches. Newer control strategies include avoiding gastric and oropharyngeal overgrowth of gram-negative bacilli by using sucralfate to avoid gastric alkalinization and/or suppressing nosocomial flora by use of topical antimicrobials.
OBJECTIVE: To investigate the possibility that contaminated commercial activated charcoal may serve as a source for fungal colonization or infection of the lower respiratory tract. DESIGN: The clinical course of a patient who aspirated commercial activated charcoal was reviewed. Fungal cultures were performed for 2 samples of an activated charcoal in sorbitol product from separate lots produced by a single manufacturer. Details of the manufacturing process were obtained from a representative of the manufacturer. SETTING: An intensive care unit in a large community teaching hospital. PATIENTS: A single patient with steroid-treated lung disease who developed a fatal pulmonary illness after aspirating a commercial activated charcoal product. RESULTS: After aspirating the charcoal product, the patient developed respiratory tract colonization and possible infection with Aspergillus niger, Paecilomyces variotii, and Penicillium species. Similar fungal species were isolated from cultures of samples obtained from two separate lots of the same commercial activated charcoal product. Several opportunities for contamination during the manufacturing process were identified. CONCLUSIONS: Physicians caring for immunocompromised patients should be aware that commercial activated charcoal products can be a source of fungal respiratory tract colonization that may mimic or cause pneumonia.
Selective decontamination of the oropharynx and gastrointestinal tract with nonabsorbable antimicrobials and sucralfate, a stress ulcer prophylactic that maintains the normal gastric acid bacterial barrier, were compared for prevention of pneumonia in a cardiac surgery intensive care unit. Over 8 months, 51 patients received selective decontamination and 56 received sucralfate. The selective decontamination regimen included polymyxin, gentamicin, and nystatin given as an oral paste and as a solution; patients also received standard antacid or histamine2 blocker stress ulcer prophylaxis. Patients in the selective decontamination group had significantly less colonization of the oropharynx and stomach by gram-negative bacilli (12% vs. 55%, P less than .001), significantly fewer infections due to gram-negative bacilli (6% vs. 20%, P = .02), and fewer infections overall (12% vs. 27%, P = .04). There was one episode of pneumonia in the selective decontamination group and five in the sucralfate group. Mortality and length of stay did not differ between the groups, but those receiving selective decontamination had less than one-third as many days of systemic antibiotic therapy with no increase in colonization or infection with resistant gram-negative bacilli. Thus, selective decontamination appeared to reduce both extrapulmonary and pulmonary infections.
Conventional infection control approaches, such as dedicated surveillance and control programs and barrier isolation techniques, effectively interrupt acquisition of many pathogens and reduce infection rates in the intensive care unit (ICU). However, a substantial proportion of infections results from endogenous rather than acquired organisms and require that we also develop strategies to prevent the progression from colonization to infection. Studies of systemic antimicrobial prophylaxis for patients at risk for pneumonia have consistently failed to demonstrate benefit. Topical endotracheal prophylaxis succeeded in preventing pneumonia but was complicated by the emergence of intrinsically resistant gram-negative bacilli. More recently, a number of trails have evaluated selective decontamination of the oropharynx and gastrointestinal tract with nonabsorbable antibiotics. These regimens have demonstrated a substantial impact on pneumonia and overall infection rates in ICU patients. Further investigation will define the role of selective decontamination in selected patient populations as well as address concerns over selection of resistance. Other strategies, including immunoprophylaxis, colonization-resistant devices, and methods to decrease bacterial adherence may also prevent progression from colonization to infection and will be the subject of future investigation.
In a multicenter, randomized clinical trial, the efficacy of ciprofloxacin plus azlocillin was compared with that of a standard regimen of ceftazidime plus amikacin for the initial empiric treatment of fever in neutropenic cancer patients. In addition, the efficacy of early conversion from intravenous therapy to orally administered ciprofloxacin was compared with that of continued ceftazidime plus amikacin. Seventy-one oncology patients with 79 episodes of fever and neutropenia were randomly assigned to receive initial empiric antibiotic therapy with either intravenously administered ciprofloxacin and azlocillin followed by orally administered ciprofloxacin (regimen 1, 25 episodes); ceftazidime and amikacin (regimen 2, 30 episodes); or ceftazidime and amikacin followed by oral ciprofloxacin (regimen 3, 24 episodes). Microbiologically documented infections were the cause of fever in 10 (40 percent), seven (23 percent), and nine (38 percent) episodes in regimens 1, 2, and 3, respectively, including six, five, and four episodes of bacteremia. Patient survival was 90 to 92 percent in each regimen; however, some modification of antimicrobial therapy occurred in 65, 44, and 41 percent of surviving patients in regimens 1, 2, and 3, respectively. The rate of clearance of initial bacteremia was 67 percent (four of six) in regimen 1, 100 percent (five of five) in regimen 2 and 50 percent (two of four) in regimen 3. Patients in regimens 1 and 3 were able to convert to orally administered ciprofloxacin in 32 (65 percent) of 49 episodes after a mean of six days of intravenous therapy. Superinfections occurred in 24, 10, and 12 percent of patients receiving regimens 1, 2, and 3, respectively, and occurred similarly for patients receiving orally administered ciprofloxacin, 12 percent (four of 32), and intravenous therapy, 17 percent (eight of 47). Parenteral ciprofloxacin was generally well tolerated. One (4 percent) of 25 patients receiving regimen 1 experienced oto- or nephrotoxicity, compared with eight (15 percent) of 54 patients receiving regimens 1, 2, and 3 (p = 0.15), including three patients who required premature termination of aminoglycoside therapy. Our data suggest that the combination of ciprofloxacin and azlocillin is an effective alternative to ceftazidime and amikacin for the initial empiric therapy of febrile neutropenic patients, is generally well tolerated, and avoids the oto- and nephrotoxicity associated with aminoglycoside use. In addition, a majority of patients could change to orally administered ciprofloxacin alone after six days of parenteral therapy.
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Bolus infusion of clotting factor concentrates remains the most common approach to the treatment or prevention of bleeding in patients with hemophilia. Although successful use of continuous infusion of such concentrates has been reported by several groups, this alternative treatment method has not achieved widespread popularity. We report here our experience in one hemophilia center with the use of continuous infusion of factor VIII and factor IX concentrates in 13 patients, 11 with hemophilia A, and 2 with hemophilia B. All patients were treated successfully for bleeding episodes (e.g., hemarthroses, intracranial, or gastrointestinal bleeding) or for surgical procedures (appendectomy, thoracotomy, etc.). Three patients with low titer factor VIII inhibitors were treated successfully with constant infusion therapy, requiring a mean dose of factor VIII concentrate 2.3 fold (8.20 u/kg/h) higher than that of the patients without inhibitors (3.63 u/kg/h) to maintain a circulating plasma level of factor VIII of 1 u/ml. The use of constant infusion of clotting factor concentrates is safe, efficacious, and more convenient than bolus therapy of factor concentrates and should be considered for hospitalized hemophilia patients requiring replacement therapy.
Pseudomonas aeruginosa colonization and infection was studied over a 6-mo period in a 36-bed mixed general medical-oncology unit. We used selective media for serial surveillance cultures on 283 patients, the environment, and personnel. Twelve percent of patients were colonized on admission and 10% acquired P. aeruginosa. Using serotyping and multilocus enzyme electrophoresis, we identified 63 genetically distinctive strains; four prevalent strains accounted for 21% of isolates. Only 5 of 33 nosocomial acquisitions were due to horizontal transmission. Nine acquisitions were linked to environmental sources (e.g., sink surfaces), which often harbored antibiotic-resistant strains but posed a risk only to oncology patients. Although significant Pseudomonas infections occurred in only 11% of colonized patients, 63% of colonized severely neutropenic patients--predominantly those who had acquired the prevalent, often environmentally linked strains--developed infections. Thus, P. aeruginosa was a significant pathogen in oncology patients; typing by multilocus enzyme electrophoresis allowed the detection of important environmental sources.
A 7-month prospective survey for cefazolin-resistant Gram-negative bacilli in cardiac surgery patients, receiving cefazolin prophylaxis, showed that 58 (67%) of 87 were colonized with enterobacter, 37 (64%) with citrobacter, 33 (57%) with Pseudomonas aeruginosa, and seven (2%) with Serratia marcescens. About 50% of colonization occurred before cefazolin prophylaxis and was present on admission to the intensive care unit. Typing of strains showed that horizontal transmission accounted for at most 14% of carriage. Cefazolin prophylaxis (and high gastric pH) were associated with increased levels of postoperative colonization, most notably for enterobacter. About 25% of colonization with enterobacter, pseudomonas, and serratia was followed by clinical infection. Enterobacter cloacae was the most common pathogen and pneumonia the most common infection. Infections contributed to eight of 11 deaths; four of the eight involved enterobacter. Potential control measures include eliminating endogenous Gram-negative flora by gut decontamination or at least stemming the increase in level of colonization that occurred after surgery.