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Gram-positive infections related to CAPD
Abstract
The majority of infections associated with continuous ambulatory peritoneal dialysis (CAPD) are caused by Gram-positive bacteria.
The coagulase-negative staphylococci are the most common cause of peritonitis and Staphylococcus aureus is the organism most frequently associated with tunnel and exit site infections. The advent of newer techniques for bag change
in CAPD has significantly reduced the incidence of peritonitis but relapse is still common among a few isolated individuals.
Carriage of staphylococci in the nose is important in predisposing individuals for exit site infections. The possibility that
eradication of nasal carriage may prevent CAPD infection has yet to be evaluated.
... First, there was an increase in S. aureus peritonitis in the IS group, with a concomitant decrease in peritonitis due to coagulase-negative staphylococci. Since S. aureus peritonitis is more severe than that due to coagulase-negative staphylococci [13], this may in part explain the difference in morbidity between the two groups. We cannot comment on the nasal carriage of S. aureus in our patients, as this was not systematically documented over this period. ...
Background
Although immunodeficiency predisposes to CAPD peritonitis with fungal or unusual organisms, the role of immunosuppression as a predisposing factor for CAPD peritonitis, as well as the outcome of such episodes, remains uncertain.
Methods
The incidence, spectrum of infectious organisms, and outcome of CAPD peritonitis was retrospectively reviewed in 39 immunosuppressed and 146 non-immunosuppressed patients treated with CAPD over the calendar year 1993.
Results
Immunosuppressed patients were younger (mean 44 vs 57 years, P<0.001) and had an increased incidence of previous transplantation, glomerulonephritis, systemic lupus erythematosus, and vasculitis. Immunosuppressed patients had more episodes of peritonitis (69/39 patients vs 99/147, P<0.001), required more frequent hospital admission (25/39 vs 33/146, P<0.001), had more days off CAPD (331 vs 242, P< 0.001), and required more laparotomies to remove infected CAPD catheters (11/39 vs 14/146, P<0.01). Immunosuppression was associated with increased infection due to S. aureus and fungi, which may have contributed towards increased morbidity in this group. Current immunosuppression or a recent history of immunosuppression appeared to be equally potent risk factors for infection. There was a trend for the incidence of infection to parallel the aggressiveness of immunosuppression.
Conclusions
Immunosuppression is an important risk factor for CAPD peritonitis. A high index of suspicion for infection and aggressive chemotherapy are mandatory. CAPD may not be the initial therapy of choice in this high-risk group.
... 17 Similarly, S aureus is a frequent cause of complicated peritonitis, and relapsed staphylococcal peritonitis episodes frequently are attributed to nasal carriage. 19,20 Eradica-tion of nasal staphylococcal colonization using topical mupirocin chemoprophylaxis has decreased the incidence of PD catheter-associated infections. 12,12,21 In contrast, isolation of fungi was significantly more likely to occur in recurrent than relapsed peritonitis. ...
... Escherichia coli) and fungi (e.g. Candida albicans) [86]. Here, IL-6 is essential for the appropriate control of acute inflammation and promotes bacterial clearance. ...
Interleukin (IL)-6 has become a major target for clinical intervention in various autoimmune conditions. Here, drugs including
the humanized anti-IL-6 receptor (IL-6R) antibody tocilizumab emphasize the clinical importance of IL-6 in driving disease
and poor patient outcomes. During the course of this review, we will outline the biology surrounding IL-6 and discuss the
impact of IL-6 in renal disease and the clinical complications associated with renal replacement therapies and transplantation.
We will also consider the merit of IL-6 measurement as a prognostic indicator and provide a clinical perspective on IL-6-blocking
therapies in renal disease.
... These infections are commonly monomicrobial, and the infecting organism is primarily determined by patient demographics . For example, healthy young girls are most often infected by streptococcal organisms, cirrhotics by gram negative or enterococcal organisms, and peritoneal dialysis patients by Staphylococcus aureus [7,8] . Diagnosis requires peritoneal fluid aspiration. ...
ABSTRACT: Intra-abdominal infection (IAI) is an important cause of morbidity and mortality. It is the second most commonly identified cause of severe sepsis in the intensive care unit and it has been associated with a high mortality rate. Most IAI are the result of inflammation and perforations of the gastrointestinal tract, such as appendicitis, peptic ulcer disease, and diverticulitis. Successful treatment of IAI is based on early and appropriate source recognition, containment and antimicrobial coverage. We will review the pathophysiology of IAI and provide clinical guidelines for its management.
The purpose of this study was to analyse the microbiological characteristics of infectious peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. This study was conducted at the CHU Nancy from 1999 to 2002. The diagnosis of peritonitis was based on cloudy peritoneal effluent (>100 cells per mm3) with an elevated leukocyte count (>50%), on isolation of bacteria or fungi and on symptoms such as abdominal discomfort or pain. The majority of infections associated with continuous ambulatory peritoneal dialysis were caused by Gram-positive bacteria (68%), Gram-negative bacteria (31%), and Candida (1%). The coagulase-negative staphylococci were the most common cause of peritonitis. The antibiotic sensitivity of species corresponded to community-acquired isolation.
Catheter-related infection is one of the most important causes of technical dropout in peritoneal dialysis patients. Both the type of cultured organism and the extent of inflammation are well known prognostic factors for the outcome of these infections. From December 1994 to November 1996, 96 catheter-related infections without simultaneous peritonitis occurred in 49 of 86 peritoneal dialysis patients treated in this study. During the observation period, only single-cuff catheters were used. Staphylococcus aureus was the most common organism cultured (51%). Involvement of the tunnel was diagnosed by sonography in 57.1% of all Staphylococcus aureus cases, but only in 26.1% of Staphylococcus epidermidis-related exit-site infections. Ten of the 96 catheter-related infections (10.4%) resulted in catheter loss. Catheter removal was necessary only in cases of deep tunnel infection caused by Staphylococcus aureus. The number of gram-negative catheter infections was too small to allow conclusive analysis. Although sonography of the catheter tunnel is now well established in the early diagnosis of tunnel infections, no clear guidelines exist for management of these infections. In this study, patients with deep tunnel infection who did not require catheter removal showed a significant decline of the hypoechogenic area around the cuff (from 7.02 +/- 0.70 to 3.75 +/- 1.04 mm, P < 0.002) 2 wk after initiation of therapy. No significant decline was observed in patients who later lost their catheters. On the basis of these data, it is concluded that in cases of exit-site and superficial tunnel infection, conservative treatment should be performed. In cases of deep tunnel infection without peritonitis caused by Staphylococcus aureus, antibiotic treatment should be started and sonographic examination should be performed every second week. If the hypoechogenic area around the cuff decreases (> 30%), conservative treatment should be prolonged. In cases without sonographic improvement (< 30%) 2 wk after therapy, catheter removal is recommended.
The causes, predictors, treatment, and outcomes of relapsed and recurrent peritoneal dialysis (PD)-associated peritonitis are poorly understood.
Observational cohort study using Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry data.
All Australian PD patients between October 1, 2003, and December 31, 2007, with first episodes of peritonitis.
Demographic, clinical, and facility variables and type of peritonitis; relapse (same organism or culture-negative episode occurring within 4 weeks of completion of therapy of a prior episode or 5 weeks if vancomycin used); recurrence (different organism occurring within 4 weeks of completion of therapy of a prior episode or 5 weeks if vancomycin used); control (first peritonitis episode without relapse or recurrence).
Hospitalization, catheter removal, hemodialysis therapy transfer, death.
Of 6,024 PD patients studied, first episodes of relapsed, recurrent, and control peritonitis occurred in 356, 165, and 2,021 patients, respectively. Coagulase-negative staphylococci and Staphylococcus aureus accounted for 48% of relapsing peritonitis (adjusted OR, 1.26 [95% CI, 0.94-1.70] and 1.54 [95% CI, 1.08-2.19], respectively), but were much less likely to be isolated in recurrent peritonitis. Recurrent peritonitis was associated more frequently with fungi (13%; OR, 2.16; 95% CI, 1.12-4.17). The empirical antimicrobial approaches to relapsing and recurrent peritonitis were similar and their subsequent clinical outcomes were comparable. Compared with uncomplicated peritonitis, relapsed and recurrent peritonitis were associated with higher rates of catheter removal (22% vs 30% vs 37%, respectively; P < 0.001) and permanent hemodialysis therapy transfer (20% vs 25% vs 32%; P < 0.001), but similar rates of hospitalization (73% vs 70% vs 70%) and death (2.8% vs 2.0% vs 1.2%).
Limited covariate adjustment. Residual confounding and coding bias could not be excluded.
Relapsed and recurrent peritonitis are caused by different spectra of micro-organisms, but are not readily clinically distinguishable at presentation. Empirical treatment with broad-spectrum antibiotics and subsequent adjustment according to antimicrobial susceptibilities results in similar clinical outcomes, albeit with appreciably higher rates of catheter removal and hemodialysis therapy transfer than for uncomplicated peritonitis.
Although immunodeficiency predisposes to CAPD peritonitis with fungal or unusual organisms, the role of immunosuppression as a predisposing factor for CAPD peritonitis, as well as the outcome of such episodes, remains uncertain.
The incidence, spectrum of infectious organisms, and outcome of CAPD peritonitis was retrospectively reviewed in 39 immunosuppressed and 146 non-immunosuppressed patients treated with CAPD over the calendar year 1993.
Immunosuppressed patients were younger (mean 44 vs 57 years, P<0.001) and had an increased incidence of previous transplantation, glomerulonephritis, systemic lupus erythematosus, and vasculitis. Immunosuppressed patients had more episodes of peritonitis (69/29 patients vs 99/147, P<0.001), required more frequent hospital admission (25/39 vs 33/146, P<0.001), had more days off CAPD (331 vs 242, P<0.001), and required more laparotomies to remove infected CAPD catheters (11/39 vs 14/146, P<0. 01). Immunosuppression was associated with increased infection due to S.aureus and fungi, which may have contributed towards increased morbidity in this group. Current immunosuppression or a recent history of immunosuppression appeared to be equally potent risk factors for infection. There was a trend for the incidence of infection to parallel the aggressiveness of immunosuppression.
Immunosuppression is an important risk factor for CAPD peritonitis. A high index of suspicion for infection and aggressive chemotherapy are mandatory. CAPD may not be the initial therapy of choice in this high-risk group.
The importance of Staphylococcus aureus as etiological agent for catheter-related infections and peritonitis in peritoneal dialysis patients is well established. To evaluate groups at risk of developing Staphylococcus aureus infections, nasal and exit-site cultures were performed in 76 peritoneal dialysis patients monthly over a period of 3 yr. The risk of Staphylococcus aureus catheter infection was significantly higher in diabetic (group 1) and immunosuppressed (group 2) patients compared with nondiabetic and nonimmunosuppressed (group 3) patients. In diabetic patients, Staphylococcus aureus-positive nasal cultures were more frequent than positive cultures taken from the bland exit-site (73.3% versus 60.0%). On the other hand, both positive and negative exit-site cultures had a better prognostic value for Staphylococcus aureus catheter infection compared with nasal cultures. In immunosuppressed patients, both nasal and exit-site carriages were associated with a very high risk of Staphylococcus aureus catheter infection, but nasal swabs were far more often positive than swabs from the bland exit-site (72.7% versus 25.0%). However, the risk of infection was also high for non-nasal and non-exit-site carriers in this group. In nondiabetic and nonimmunosuppressed patients, the risk of Staphylococcus aureus catheter infection was increased only if two or more positive nasal cultures were detected. It is concluded that in diabetic patients, antibiotic prophylaxis should be performed in all Staphylococcus aureus exit-site carriers. All immunosuppressed patients should be treated prophylactically. In contrast, in nondiabetic and nonimmunosuppressed patients, prophylactic treatment should be considered only in nasal carriers with two or more positive cultures. The overall low peritonitis rate does not influence this prevention strategy.
Infections with gram-positive bacteria are a major cause of morbidity and mortality in humans. Opsonin-dependent phagocytosis plays a major role in protection against and recovery from gram-positive infections. Inborn and acquired defects in opsonin generation and/or recognition by phagocytes are associated with an increased susceptibility to bacterial infections. In contrast, the physiological significance of opsonin-independent phagocytosis is unknown. Type I and II class A scavenger receptors (SR-AI/II) recognize a variety of polyanions including bacterial cell wall products such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), suggesting a role for SR-AI/II in innate immunity to bacterial infections. Here, we show that SR-AI/II-deficient mice (MSR-A(-/-)) are more susceptible to intraperitoneal infection with a prototypic gram-positive pathogen, Staphylococcus aureus, than MSR-A(+/+) control mice. MSR-A(-/-) mice display an impaired ability to clear bacteria from the site of infection despite normal killing of S. aureus by neutrophils and die as a result of disseminated infection. Opsonin-independent phagocytosis of gram-positive bacteria by MSR-A(-/-) macrophages is significantly decreased although their phagocytic machinery is intact. Peritoneal macrophages from control mice phagocytose a variety of gram-positive bacteria in an SR-AI/II-dependent manner. Our findings demonstrate that SR-AI/II mediate opsonin-independent phagocytosis of gram-positive bacteria, and provide the first evidence that opsonin-independent phagocytosis plays a critical role in host defense against bacterial infections in vivo.
Peritonitis is the most important complication of continuous ambulatory peritoneal dialysis (CAPD). Coagulase-negative staphylococci (CNS) are the most common causes of peritonitis, only limited information is available regarding the distribution and epidemiology of different CNS species associated with CAPD peritonitis.
CNS isolated from dialysis effluent from CAPD patients with peritonitis was identified by species and further analyzed with pulsed-field gel electrophoresis (PFGE).
A total of 216 microorganisms (206 bacteria and 10 Candida species) were isolated from 196 consecutive culture-positive CAPD samples obtained from 75 patients. One hundred and twenty-one (56%) isolates represented staphylococci. The four most frequently isolated staphylococcal species were Staphylococcus epidermidis (70 isolates), Staphylococcus aureus (31 isolates), Staphylococcus hemolyticus (10 isolates), and Staphylococcus hominis (4 isolates). PFGE analysis revealed the clonal spread among patients of three different clones of S. epidermidis and one clone of S. aureus among the investigated patients. Indistinguishable isolates of either S. epidermidis, S. hominis, or S. aureus were also isolated in repeated samples from several patients.
PFGE is a useful method for the epidemiological evaluation of staphylococci-associated CAPD infections and should replace older and less accurate methods, such as antibiotic sensitivity patterns. We recommend that CNS isolates from patients with CAPD-associated peritonitis should be saved for future investigations and typing, which would aid in the management of this patient category.
Unlabelled:
Clarithromycin is an orally active, advanced-generation macrolide that has been reformulated as an extended-release tablet (Biaxin) XL Filmtab allowing convenient once-daily administration. The reformulation is intended to improve patient compliance and the tolerability of the drug. Although maximum plasma clarithromycin concentrations are lower and reached later with the extended-release tablets than with the immediate-release tablets, the two formulations are bioequivalent with respect to the area under the plasma concentration-time curve. Bioequivalence is also achieved between the formulations for the microbiologically active metabolite, 14-hydroxy-clarithromycin. Two randomized trials in patients with acute exacerbations of chronic bronchitis (AECB) showed that a 7-day course of clarithromycin extended-release 1000 mg once daily produced clinical cure rates of 83% and 85% and bacteriologic cure rates of 86% and 92% at the test-of-cure study visit. Similar rates of cure were achieved with a 7-day course of twice-daily clarithromycin immediate-release and with a 10-day course of twice-daily amoxicillin/clavulanic acid.A 7-day course of clarithromycin extended-release 1000 mg once daily produced clinical and bacteriologic cure rates of 88% and 86%, respectively, in patients with community-acquired pneumonia (CAP). Similar cure rates were achieved in recipients of once-daily levofloxacin in the same trial. In patients with acute maxillary sinusitis, a 14-day course of either once-daily clarithromycin extended-release or twice-daily clarithromycin immediate-release produced statistically equivalent clinical cure rates of 85% and 79%, respectively. Both treatment groups achieved similar rates of radiographic success and resolution of sinusitis. Recent results indicate that clarithromycin extended-release 500 mg once daily for 5 days is also effective in the treatment of patients with streptococcal pharyngitis/tonsillitis and in the treatment of AECB. The most frequently reported drug-related events with clarithromycin extended-release were abnormal taste (7% incidence), diarrhea (6%) and nausea (3%). Most adverse drug reactions were of a mild and transient nature. In comparative clinical trials, clarithromycin extended-release had an improved gastrointestinal tolerability profile compared with the immediate-release formulation. In addition, clarithromycin extended-release was better tolerated than amoxicillin/clavulanic acid and as well tolerated as levofloxacin. Further studies are required to assess the cost-effectiveness ratio of clarithromycin relative to comparator antibacterial agents.
Conclusion:
Clarithromycin extended-release is an effective treatment for AECB, CAP, acute maxillary sinusitis, and pharyngitis (although not approved for the latter in the US), and is administered in a convenient dosage regimen that has the potential to encourage good compliance. The reformulation modulates clarithromycin absorption kinetics thereby improving tolerability. Therefore, clarithromycin extended-release provides a useful option for the treatment of specific respiratory tract infections.
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