Pneumo-peritoneum following PEG insertion: a clinical dilemma.

We present the case of a 48 year old male with multiple sclerosis who later became unwell with fever and vague abdominal pain 2 days after inserting a percutanous endoscopic gastrostomy (PEG) tube. His chest x-ray showed gas under the diaphragm. As a result of this, a laparotomy was performed which found no evidence of intra-abdominal sepsis. We discuss the importance of recognising 'benign' pneumoperitoneum following PEG insertion. Further imaging, such as abdominal CT scan is desirable prior to consideration of laparotomy when diagnostic uncertainty exists.

Acapella versus 'usual airway clearance' during acute exacerbation in bronchiectasis: a randomized crossover trial.

Devices such as the Acapella may facilitate independent airway clearance, however, few clinical trials have investigated the efficacy of Acapella. The aim of this study was to compare the effectiveness of Acapella to 'usual airway clearance' in adults during an acute exacerbation of bronchiectasis requiring oral antibiotic therapy. Twenty patients with bronchiectasis and an acute exacerbation requiring oral antibiotic therapy were recruited into a randomized crossover trial. Patients were allocated to one of two groups determined by concealed computer generated randomization. Group 1 (n=10): airway clearance session using Acapella at home twice daily during oral antibiotic therapy. Group 2 (n=10): 'usual' airway clearance sessions at home during oral antibiotic therapy. Patients recorded duration of each treatment session, volume of sputum produced and perception of breathlessness. An independent assessor performed outcome measures of spirometric lung function, pulse oximetry and breathlessness at the beginning and end of the study period. The mean volume of sputum expectorated during Acapella sessions was greater than for usual airway clearance sessions although this difference was not significant 2.61 ml (95% CI-1.62 to 6.84). Mean duration of Acapella sessions was greater than usual airway clearance sessions and approached significance. There were no significant between group differences in changes in lung function. This study demonstrates that the Acapella device may offer an acceptable, user-friendly method of airway clearance in patients with bronchiectasis.

Antibiotic cycling to decrease bacterial antibiotic resistance: a 5-year experience on a bone marrow transplant unit.

Multidrug-resistant pathogens have important effects on clinical outcomes. Antibiotic cycling is one approach to control anti-microbial resistance, but few studies have examined cycling in hematology-oncology units. Antibiotic cycling was implemented in January 1999 at our hematology-oncology unit, alternating piperacillin-tazobactam (pip-tazo) and cefepime in 3 months periods, until June 2004. Clinical isolates were compared in post- and pre-intervention periods and with the susceptibility among the solid organ transplant intensive care unit (TICU) isolates. The rate of Gram-negative isolates remained stable. Among Gram-negatives, susceptibility to cefepime and pip-tazo remained stable. There was an increase in Enterococcus spp. (P=0.007), and susceptibility to ampicillin and vancomycin decreased (odds ratio (OR): 0.04, 95% confidence interval (CI): 0.17-0.89 and OR: 0.23, 95% CI: 0.09-0.58). Compared with the TICU, there was increased susceptibility to pip-tazo and cefepime among enterics (OR: 7.32, 95% CI: 4.44-12.07 and OR: 8.82, 95% CI: 2.1-37.13) and Pseudomonas aeruginosa (OR: 4.27, 95% CI: 1.47-12.4 and OR: 4.61, 95% CI: 1.75-12.1) and decreased susceptibility to ampicillin and vancomycin among enterococci (OR: 0.44, 95% CI: 0.30-0.63 and OR: 0.38, 95% CI: 0.26-0.56). Cycling was associated with preserved antibiotic susceptibility among Gram-negatives, but with an increase in Enterococcus spp. and vancomycin and ampicillin resistance among enterococci.

Airway clearance in bronchiectasis: a randomized crossover trial of active cycle of breathing techniques (incorporating postural drainage and vibration) versus test of incremental respiratory endurance.

OBJECTIVES: The purpose of this study was to compare the efficacy of the test of incremental respiratory endurance (TIRE) with active cycle of breathing techniques (ACBT) [incorporating postural drainage (PD) and vibration] as methods of airway clearance in adults with bronchiectasis. DESIGN: A randomized crossover study in which a single session of ACBT (incorporating PD and vibration) was compared to a single session of TIRE was carried out in 20 patients (14 female) with stable, productive bronchiectasis. MEASUREMENTS: Weight of sputum (treatment plus 30 min) was the primary outcome measure recorded. Pre- and post-treatment measures of lung function and SpO2 were also recorded. RESULTS: All 20 patients were stable during the study period. Sputum weight expectorated during and 30 min post-ACBT (incorporating PD and vibration) treatment was significantly greater than the sputum weight expectorated during and 30 min post-TIRE treatment [mean difference 2.44 g (95% CI 0.43-4.45)]. CONCLUSION: ACBT (incorporating PD and vibration) is a more effective method of airway clearance in bronchiectasis than TIRE during single treatment sessions.

Risk factors for Candida species colonization of neonatal intensive care unit patients.

BACKGROUND: Candida spp. are increasingly important pathogens in neonatal intensive care units (NICU). Prior colonization is a major risk factor for candidemia, but few studies have focused on risk factors for colonization, particularly in NICU patients. METHODS: A prospective, multicenter cohort study was performed in six NICUs to determine risk factors for Candida colonization. Infant gastrointestinal tracts were cultured on admission and weekly until NICU discharge and health care worker hands were cultured monthly for Candida spp. RESULTS: The prevalence of Candida spp. colonization was 23% (486 of 2157 infants); 299 (14%), 151 (7%) and 74 (3%) were colonized with Candida albicans, Candida parapsilosis and other Candida spp., respectively. Multiple logistic regression analysis adjusting for length of stay, birth weight < or = 1000 g and gestational age < 32 weeks revealed that use of third generation cephalosporins was associated with either C. albicans (155 incident cases) or C. parapsilosis (104 incident cases) colonization. Use of central venous catheters or intravenous lipids were risk factors for C. albicans, whereas delivery by cesarean section was protective. Use of H2 blockers was an independent risk factor for C. parapsilosis. Of 2989 cultures from health care workers' hands, 150 (5%) were positive for C. albicans and 575 (19%) for C. parapsilosis, but carriage rates did not correlate with NICU site-specific rates for infant colonization. CONCLUSIONS: We speculate that NICU patients acquire Candida spp., particularly C. parapsilosis, from the hands of health care workers. H2 blockers, third generation cephalosporins and delayed enteral feedings alter gastrointestinal tract ecology, thereby facilitating colonization.

Clinical outcomes of bacteremic pneumococcal pneumonia in the era of antibiotic resistance.

Limited data are available about the impact of antimicrobial resistance on clinical outcomes in cases of pneumococcal pneumonia. This was studied in 146 persons hospitalized with invasive pneumonia due to Streptococcus pneumoniae (minimum inhibitory concentration of cefotaxime, > or = .25 microg/mL) who were identified through population-based active surveillance for the period of November 1994 through April 1996. Compared with matched control subjects who had infection with more-susceptible S. pneumoniae, the proportion of subjects who died or who were admitted to an intensive care unit did not differ significantly. Multivariable analysis showed no significant contribution of antimicrobial resistance to mortality or the requirement for care in an intensive care unit. The ability to detect an effect of antimicrobial resistance on these important outcome measures may have been influenced by aggressive multidrug empirical therapy in this group of hospitalized patients. Factors other than resistance, such as severity of illness at presentation and advance directive status ("do not resuscitate" orders), appear to have a stronger influence on pneumococcal pneumonia outcomes.

Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis Survey.

To assess risk factors for development of candidal blood stream infections (CBSIs), a prospective cohort study was performed at 6 sites that involved all patients admitted to the surgical intensive care unit (SICU) for >48 h over a 2-year period. Among 4276 such patients, 42 CBSIs occurred (9.82 CBSIs per 1000 admissions). The overall incidence was 0.98 CBSIs per 1000 patient days and 1.42 per 1000 SICU days with a central venous catheter in place. In multivariate analysis, factors independently associated with increased risk of CBSI included prior surgery (relative risk [RR], 7.3), acute renal failure (RR, 4.2), receipt of parenteral nutrition (RR, 3.6), and, for patients who had undergone surgery, presence of a triple lumen catheter (RR, 5.4). Receipt of an antifungal agent was associated with decreased risk (RR, 0.3). Prospective clinical studies are needed to identify which antifungal agents are most protective and which high-risk patients will benefit from antifungal prophylaxis.

Antimicrobial resistance from enterococci in a pediatric hospital. Plasmids in Enterococcus faecalis isolates with high-level gentamicin and streptomycin resistance.

BACKGROUND: Enterococcus spp. is an important nosocomial and community-acquired pathogen. Recent studies have documented the increasing importance of this pathogen in children, particularly in the hospital setting. Our objective in this study was to report the frequency of antimicrobial resistance in enterococci and to determine the characteristics of high-level gentamicin resistance (HLGR) plasmids in Enterococcus faecalis clinical isolates. METHODS: Two hundred eighty-nine enterococcal isolates were collected during an 18-month period from a tertiary-care pediatric hospital in Mexico City. Isolates were screened for antibiotic resistance, including HLGR. High-level, gentamicin-resistant E. faecalis strains were selected for pulsed-field electrophoresis (PFGE) typing and plasmid analysis. Transferability of resistance markers was carried out using filter matings. RESULTS: Seventy-six percent of isolates were E. faecalis, 10% were E. avium, 5.2% E. faecium, 5.2% E. raffinossus, 1.38% E. malodoratus, 0.6% E. hirae, and 0.6% E. casseliflavus. Antimicrobial resistance was ampicillin and penicillin 29%, imipenem 17%, and vancomycin 3%, HLGR 5%. The following 15 high-level, gentamicin-resistant isolates were identified: six E. faecalis; four E. avium; three E. faecium, and two E. casseliflavus. Five of the six E. faecalis isolates were different by PFGE and transferred gentamicin and streptomycin resistance on filter membranes. Transfer frequencies ranged from 8.2 x 10(-4) to 6.92 x 10(-5) transconjugants/recipient cell. The plasmid content of donors and transconjugants were homogeneous (one plasmid of 47 kb). CONCLUSIONS: In this pediatric hospital, antimicrobial resistance in Enterococcus spp. is common. Frequency of high-level, gentamicin-resistant strains is low. Mechanism of HLGR appears to be due to a single plasmid dissemination.

Antibiotic utilization: is there an effect on antimicrobial resistance?

The antimicrobial resistance problem in hospitals continues to worsen. In particular, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) and vancomycin-resistant enterococci (VRE) are significant causes of morbidity and mortality among critically ill patients. Treating infections caused by these pathogens presents therapeutic dilemmas. The association between broad-spectrum beta-lactam overutilization and selection for ESBL-KP has been appreciated for some time; several institutions have reported a decrease in the prevalence of ESBL-KP with a shift in antibiotic utilization from third-generation cephalosporins to other broad-spectrum drugs. Currently, optimal treatment of ESBL-KP includes the carbapenems, but widespread use of these drugs is expensive and may be associated with further selection of antibiotic resistance and/or superinfection with other inherently resistant pathogens. VRE are especially difficult organisms to treat because of their inherent and acquired resistance to most currently available antibiotics. The prevalence of VRE has also been documented to decrease upon a shift in antibiotic use from third-generation cephalosporins to broad-spectrum antibiotics of other classes. Thus, antibiotic utilization measures appear to contribute to the control of the emergence of multidrug-resistant pathogens such as ESBL-KP and VRE.

Extended-spectrum beta-lactamases. An overview.

The emergence of extended-spectrum beta-lactamase (ESBL)- producing Klebsiella pneumoniae and other ESBL-producing Enterobacteriaceae is an increasing problem and presents a dilemma for clinicians. The problem is not only detection of this resistance in the microbiology laboratory, but also a therapeutic dilemma due to multiple drug resistance to extended-spectrum beta-lactams and other agents, including fluoroquinolones, trimethoprim-sulfamethoxazole, and gentamicin. Currently, imipenem appears to be the drug of choice for serious infections due to these isolates, based on accumulating clinical experience. Because options for therapy are limited, control and prevention measures are particularly important. These should include not only traditional infection control measures such as contact precautions, but also antibiotic utilization measures, such as widespread empiric use of ceftazidime.

Fatty acid amide hydrolase substrate specificity.

Fatty acid amide hydrolase (FAAH), also referred to as oleamide hydrolase and anandamide amidohydrolase, is a serine hydrolase responsible for the degradation of endogenous oleamide and anandamide, fatty acid amides that function as chemical messengers. FAAH hydrolyzes a range of fatty acid amides, and the present study examines the relative rates of hydrolysis of a variety of natural and unnatural fatty acid primary amide substrates using pure recombinant rat FAAH.

Association of antibiotic utilization measures and control of multiple-drug resistance in Klebsiella pneumoniae.

OBJECTIVE: To study the association of antibiotic-utilization measures and control of multidrug-resistant (MDR) Klebsiella pneumoniae after emergence in two hospitals in our medical center. DESIGN AND SETTING: Rates of MDR K. pneumoniae at two hospitals were compared before and after acute interventions, including emphasis on Contact Precautions and education in antibiotic utilization. Antipseudomonal beta-lactam antibiotic use was measured before and after the interventions at both hospitals. Pulsed-field gel electrophoresis of whole cell DNA was used as a marker of strain identity. RESULTS: Clonal strain dissemination was the major mechanism of emergence at hospital A; emergence was polyclonal at hospital B. Antibiotic-utilization interventions at both institutions included physician education regarding the association of ceftazidime use and MDR K. pneumoniae. At hospital A, ceftazidime use decreased from 4,301 g in the preintervention period, to 1,248 g in the postintervention period. Piperacillin-tazobactam use increased from 12,455 g to 17,464 g. Ceftazidime resistance in K. pneumoniae decreased from 110 (22%) of 503 isolates to 61 (15%) of 407 isolates (P<.05); piperacillin-tazobactam resistance decreased from 181 (36%) of 503 to 77 (19%) of 407 isolates (P<.05). At hospital B, ceftazidime use decreased from 6,533 g in the preintervention period to 4,792 g in the postintervention period. Piperacillin-tazobactam use increased from 58,691 g to 67,027 g. Ceftazidime resistance in K. pneumoniae decreased from 42 (10%) of 415 isolates to 19 (5%) of 383 isolates (P<.05). Piperacillin-tazobactam resistance decreased from 91 (22%) of 415 isolates to 54 (14%) of 383 isolates (P<.05). Follow-up data showed continued decrease in piperacillin-tazobactam resistance despite increased use at both hospitals. CONCLUSIONS: Antibiotic-use measures may be particularly important for control of MDR K. pneumoniae, whether emergence is clonal or polyclonal.

Risk factors for candidemia in Neonatal Intensive Care Unit patients. The National Epidemiology of Mycosis Survey study group.

BACKGROUND: Candida species are important nosocomial pathogens in neonatal intensive care unit (NICU) patients. METHODS: A prospective cohort study was performed in six geographically diverse NICUs from 1993 to 1995 to determine the incidence of and risk factors for candidemia, including the role of gastrointestinal (GI) tract colonization. Study procedures included rectal swabs to detect fungal colonization and active surveillance to identify risk factors for candidemia. Candida strains obtained from the GI tract and blood were analyzed by pulsed field gel electrophoresis to determine whether colonizing strains caused candidemia. RESULTS: In all, 2,847 infants were enrolled and 35 (1.2%) developed candidemia (12.3 cases per 1,000 patient discharges or 0.63 case per 1,000 catheter days) including 23 of 421 (5.5%) babies < or =1,000 g. After adjusting for birth weight and abdominal surgery, forward multivariate logistic regression analysis demonstrated significant risk factors, including gestational age <32 weeks, 5-min Apgar <5; shock, disseminated intravascular coagulopathy, prior use of intralipid, parenteral nutrition, central venous catheters, H2 blockers, intubation or length of stay > 7 days before candidemia (P < 0.05). Catheters, steroids and GI tract colonization were not independent risk factors, but GI tract colonization preceded candidemia in 15 of 35 (43%) case patients. CONCLUSIONS: Candida spp. are an important cause of late onset sepsis in NICU patients. The incidence of candidemia might be decreased by the judicious use of treatments identified as risk factors and avoiding H2 blockers.

Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995-1997.

OBJECTIVES: This study examined epidemiologic factors affecting mortality from pneumococcal pneumonia in 1995 through 1997. METHODS: Persons residing in a surveillance area who had community-acquired pneumonia requiring hospitalization and Streptococcus pneumoniae isolated from a sterile site were included in the analysis. Factors affecting mortality were evaluated in univariate and multivariate analyses. The number of deaths from pneumococcal pneumonia requiring hospitalization in the United States in 1996 was estimated. RESULTS: Of 5837 cases, 12% were fatal. Increased mortality was associated with older age, underlying disease. Asian race, and residence in Toronto/Peel, Ontario. When these factors were controlled for, increased mortality was not associated with resistance to penicillin or cefotaxime. However, when deaths during the first 4 hospital days were excluded, mortality was significantly associated with penicillin minimum inhibitory concentrations of 4.0 or higher and cefotaxime minimum inhibitory concentrations of 2.0 or higher. In 1996, about 7000 to 12,500 deaths occurred in the United States from pneumococcal pneumonia requiring hospitalization. CONCLUSIONS: Older age and underlying disease remain the most important factors influencing death from pneumococcal pneumonia. Mortality was not elevated in most infections with beta-lactam-resistant pneumococci.

Clinical outcomes of meningitis caused by Streptococcus pneumoniae in the era of antibiotic resistance.

Limited data are available on clinical outcomes of meningitis due to cefotaxime-nonsusceptible Streptococcus pneumoniae. We analyzed data from 109 cases of pneumococcal meningitis in Atlanta, Baltimore, and San Antonio, which were identified through population-based active surveillance from November 1994 to April 1996. Pneumococcal isolates from 9% of the cases were resistant to cefotaxime, and isolates from 11% had intermediate susceptibility. Children were more likely to have cephalosporin-nonsusceptible pneumococcal meningitis, but mortality was significantly higher among adults aged 18-64 years. Vancomycin was given upon admission to 29% of patients, and within 48 h of admission to 52%. Nonsusceptibility to cefotaxime was not associated with the following outcomes: increased mortality, prolonged length of hospital or intensive care unit (ICU) stay, requirement of intubation or oxygen, ICU care, discharge to another medical or long-term-care facility, or neurological deficit. Empirical use of vancomycin, current prevalence of drug-resistant S. pneumoniae, and degree of nonsusceptibility to cefotaxime may have influenced these findings.

Extended-spectrum beta-lactamases.

Resistance to broad-spectrum cephalosporins among Klebsiella pneumoniae has increased significantly, particularly in the intensive care unit setting, in the past decade. The problem has been noted not only in the United States, but around the world. A major mechanism responsible for this is the emergence of extended-spectrum beta-lactamases (ESBLs). These plasmid-mediated beta-lactamases confer resistance to broad-spectrum beta-lactam antibiotics, including third- and fourth-generation cephalosporins, aztreonam, and extended-spectrum penicillins. Other resistances, such as aminoglycoside and trimethoprim-sulfamethoxazole resistance, are often cotransferred on the same plasmid. Fluoroquinolone resistance is also frequently associated, resulting in an organism resistant to most broad-spectrum options. The carbapenems are currently considered the drug of choice for these pathogens. Prevention and control measures are important because of the multiresistant nature of these pathogens. Such traditional infection control measures as contact precautions are recommended. In addition, because this type of antimicrobial resistance appears to be particularly influenced by antibiotic use, antibiotic control measures may also be a very important intervention in controlling the spread of ESBLs.

Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients.

Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991-92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community-acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre-intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high-risk solid organ transplant patients.

Elucidating the origins of nosocomial infections with Candida albicans by DNA fingerprinting with the complex probe Ca3.

Computer-assisted DNA fingerprinting with the complex probe Ca3 has been used to analyze the relatedness of isolates collected from individuals with nosocomial bloodstream infections (BSIs) and hospital care workers (HCWs) in the surgical and neonatal intensive care units (ICUs) of four hospitals. The results demonstrate that for the majority of patients (90%), isolates collected from commensal sites before and after collection of a BSI isolate were highly similar or identical to the BSI isolate. In addition, the average similarity coefficient for BSI isolates was similar to that for unrelated control isolates. However, the cluster characteristics of BSI isolates in dendrograms generated for each hospital compared to those of unrelated control isolates in a dendrogram demonstrated a higher degree of clustering of the former. In addition, a higher degree of clustering was observed in mixed dendrograms for HCV isolates and BSI isolates for each of the four test hospitals. In most cases, HCW isolates from an ICU were collected after the related BSI isolate, but in a few cases, the reverse was true. Although the results demonstrate that single, dominant endemic strains are not responsible for nosocomial BSIs in neonatal ICUs and surgical ICUs, they suggest that multiple endemic strains may be responsible for a significant number of cases. The results also suggest that cross-contamination occurs between patients and HCWs and between HCWs in the same ICU and in different ICUs. The temporal sequence of isolation also suggests that in the majority of cases HCWs are contaminated by isolates from colonized patients, but in a significant minority, the reverse is true. The results of this study provide the framework for a strategy for more definitive testing of the origins of Candida albicans strains responsible for nosocomial infections.

N-acylglycine amidation: implications for the biosynthesis of fatty acid primary amides.

Bifunctional peptidylglycine alpha-amidating enzyme (alpha-AE) catalyzes the O2-dependent conversion of C-terminal glycine-extended prohormones to the active, C-terminal alpha-amidated peptide and glyoxylate. We show that alpha-AE will also catalyze the oxidative cleavage of N-acylglycines, from N-formylglycine to N-arachidonoylglycine. N-Formylglycine is the smallest amide substrate yet reported for alpha-AE. The (V/K)app for N-acylglycine amidation varies approximately 1000-fold, with the (V/K)app increasing as the acyl chain length increases. This effect is largely an effect on the KM,app; the KM,app for N-formylglycine is 23 +/- 0.88 mM, while the KM,app for N-lauroylglycine and longer chain N-acylglycines is in the range of 60-90 microM. For the amidation of N-acetylglycine, N-(tert-butoxycarbonyl)glycine, N-hexanoylglycine, and N-oleoylglycine, the rate of O2 consumption is faster than the rate of glyoxylate production. These results indicate that there must be the initial formation of an oxidized intermediate from the N-acylglycine before glyoxylate is produced. The intermediate is shown to be N-acyl-alpha-hydroxyglycine by two-dimensional 1H-13C heteronuclear multiple quantum coherence (HMQC) NMR.

Trifluoromethyl ketone inhibitors of fatty acid amide hydrolase: a probe of structural and conformational features contributing to inhibition.

The examination of a series of trifluoromethyl ketone inhibitors of Fatty Acid Amide Hydrolase (FAAH, oleamide hydrolase, anandamide amidohydrolase) is detailed in efforts that define structural and conformational properties that contribute to enzyme inhibition and substrate binding. The results imply an extended bound conformation, highlight a role for the presence, position, and stereochemistry of a delta cis double bond, and suggest little apparent role for C11-C18/C22 of the fatty acid amide substrates.