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Biomedical subjects

F Espersen

Publications and source records attributed to F Espersen.

At least 19 recordsLinked to original sources
PubMed1998

Bacteremic Staphylococcus aureus spondylitis.

BACKGROUND: The incidence of hematogenous Staphylococcus aureus osteomyelitis of the vertebral column is rapidly increasing and few studies dealing with the diagnosis, treatment, and outcome of this severe disease are available. METHODS: Based on a nationwide registration, the clinical and bacteriological data were reviewed from 133 cases with a positive blood culture for S aureus and symptoms of vertebral osteomyelitis in Denmark for the period 1980 to 1990. RESULTS: The 133 cases of vertebral S aureus osteomyelitis reviewed were mainly community-acquired infections (82%) in older patients (median age, 65 years) and often occurred with underlying diseases. Both symptoms and laboratory values were relatively unspecific. Bone scan methods proved to be more optimal for diagnosis of vertebral S aureus osteomyelitis in the early stages compared with conventional radiography that proved a lack of consistency in the formative stages. The infection was mostly (70%) localized in the lower part of the column. The recurrence rate and rate of therapeutic failure depended on the duration and dosage of penicillinase-stable penicillins, respectively. Patients treated with fusidic acid in addition to penicillinase-stable penicillins had a significantly lower recurrence rate. Based on these findings, we recommend treatment with penicillinase-stable penicillins and fusidic acid for a total of 8 weeks, with a daily dosage of penicillinase-stable penicillins higher than 4 g. CONCLUSIONS: The diagnosis of vertebral S aureus osteomyelitis based on clinical findings is difficult to ascertain. Bone scans are necessary because radiographic methods do not detect disease as early. Treatment with penicillinase-stable penicillins, at least 4 g/d for at least 8 weeks, is recommended.

Adolescent↗
PubMed1998

Pharmacodynamics of penicillin are unaffected by bacterial growth phases of Streptococcus pneumoniae in the mouse peritonitis model.

The correlation between pharmacokinetic parameters and the in-vivo effect of antibiotics in relation to bacterial growth phases was evaluated using the mouse peritonitis model with a penicillin-resistant pneumococcus. Different 8 h dosing regimens were applied, with different total doses and initiated at different times during the bacterial growth phase. The effect was measured as the decline in bacterial counts in the peritoneal cavity. The pharmacokinetic parameters showed major changes during the phases of growth, as the serum elimination of penicillin decreased during the infection. The same effect of dosing regimens was observed in the exponential and stationary phases. In two regimens where T(>MIC) (the time the serum concentration exceeded the MIC) was 50% of the treatment period, a significantly better effect was achieved with a 2 hourly regimen than with a regimen with treatments every 20 min. The T(>MIC) of each dose was shown to be a critical parameter for achieving an effect in all growth phases. The maximum effect of penicillin, a 5-6 x log10 decline in bacterial counts in the peritoneum of the mice, was achieved when T(>MIC) was >50% of the treatment time or longer than approximately 40 min of each dose. The 50% effective dose for protection after a single injection, ED50, was measured in the different phases of the infection and found to increase with the duration of the pneumococcal infection, while mice treated 24 h after challenge were beyond therapeutic range. The correlation between the effect of penicillin and pharmacokinetic parameters appears to follow the same rules during the different in-vivo growth phases of pneumococci.

Animals↗
PubMed1998

Staphylococcus aureus bacteraemia among patients undergoing dialysis--focus on dialysis catheter-related cases.

BACKGROUND: Central venous catheter-related infections are the most common cause of nosocomial S. aureus bacteraemia in Denmark. Central venous catheters are often used for dialysis, and patients on dialysis often run into staphylococcal infections. The purpose of this study was to investigate S. aureus bacteraemia among dialysis patients, especially those related to dialysis catheters. METHODS: This was a retrospective study of 14,387 consecutive S. aureus bacteraemia cases during the period 1976-93, of which 793 cases occurred among dialysis patients. By reviewing the case records, 65 dialysis catheter-related cases were described more thoroughly. RESULTS: The number of S. aureus bacteraemia cases among dialysis patients as a proportion of all cases in Denmark has increased from 5.2 to 14.7% during the study period, but the annual incidence among these patients has been almost stable during the period (median 5.7% (3.2-9.0%)). Patients on dialysis had a lower mortality than other patients with S. aureus bacteraemia (18.9 vs 29.0%), but a four times higher mortality from central venous catheter-related S. aureus bacteraemia (5.3 vs 1.3%, P < 0.001). The mortality from dialysis catheter-related S. aureus bacteraemia was correlated with greater age (median 71 years (57-73) vs median 56.5 years (15-76), P < 0.01) and with septic shock (55.5 vs 7.1%, P < 0.05). Patients on dialysis had a lower frequency of S. aureus endocarditis (3.3 vs 5.4%, P < 0.01) and of S. aureus bone and joint infections (3.3 vs 8.2%, P < 0.001) than other patients. Patients undergoing dialysis had a later onset of catheter-related S. aureus bacteraemia than other patients (median 15 days (1-145) vs 5 days (1-134), P < 0.05). CONCLUSIONS: Patients on dialysis are at a high risk of S. aureus bacteraemia and they have a four times higher mortality from central venous catheter-related S. aureus bacteraemia than other patients. There is need for prospective studies in which patients as well as catheters are followed more thoroughly to study the pathogenesis of dialysis catheter-related infections.

Adult↗
PubMed1998

Comparison of pharmacodynamics of azithromycin and erythromycin in vitro and in vivo.

In this study, we determined the efficacy of various dosing regimens for erythromycin and azithromycin against four pneumococci with different susceptibilities to penicillin in an in vitro pharmacokinetic model and in a mouse peritonitis model. The MIC was 0.03 microg/ml, and the 50% effective doses (determined after one dose) of both drugs were comparable for the four pneumococcal strains and were in the range of 1.83 to 6.22 mg/kg. Dosing experiments with mice, using regimens for azithromycin of one to eight doses/6 h, showed the one-dose regimen to give the best result; of the pharmacodynamic parameters tested (the maximum drug concentration in serum [Cmax], the times that the drug concentration in serum remained above the MIC and above the concentration required for maximum killing, and the area under the concentration time curve), Cmax was the best predictor of outcome. The bacterial counts in mouse blood or peritoneal fluid during the first 24 h after challenge were not correlated to survival of the mice. The serum concentration profiles obtained with mice for the different dosing regimens were simulated in the in vitro pharmacokinetic model. Here as well, the one-dose regimen of azithromycin showed the best result. However, the killing curves in vivo in mouse blood and peritoneal fluid and in the vitro pharmacokinetic model were not similar. The in vitro killing curves showed a decrease of 2 log10 within 2 and 3 h for azithromycin and erythromycin, respectively whereas the in vivo killing curves showed a bacteriostatic effect for both drugs. It is concluded that the results in terms of predictive pharmacodynamic parameters are comparable for the in vitro and in vivo models and that high initial concentrations of azithromycin favor a good outcome.

Animals↗
PubMed1997

Neurologic manifestations in Staphylococcus aureus endocarditis: a review of 260 bacteremic cases in nondrug addicts.

PURPOSE: To investigate the neurologic manifestations of infective endocarditis caused by Staphylococcus aureus in a population of nondrug addicts with special emphasis on the clinical presentation, epidemiology, and mortality. PATIENTS AND METHODS: During the period from 1982 to 1991 a total of 8,514 cases of bacteremia with S aureus were reported to the Staphylococcus Laboratory, Copenhagen, Denmark. The medical records of cases of suspected infective endocarditis were retrospectively reviewed and classified according to the new diagnostic criteria for endocarditis proposed by Durack. RESULTS: A total of 260 cases from 63 hospitals fulfilled the diagnostic criteria. Overall, 91 patients (35%) experienced neurologic manifestations. Sixty-one presented with neurologic symptoms, whereas 30 patients developed neurologic complications at various intervals (median: 10 days) after the debut of the disease. The most frequent neurologic manifestation was unilateral hemiparesis, which occurred in 41 patients (45%). Forty-two percent of the females had neurologic manifestations compared to only 30% of the males (P = 0.06). Cases with native mitral valve infection had a significantly higher frequency of neurologic manifestations compared with all other valvular involvement (44% versus 29%, P = 0.02) but the frequency of neurologic complications was only nonsignificantly higher in those patients with native mitral valve infection than in those patients with native aortic valve infection (44% versus 31%, P = 0.10). Only two of the patients with tricuspid valve infection and none of those with congenital heart disorder experienced neurologic manifestations. A neurologic manifestation occurred in 22 (35%) of the 63 episodes in which vegetations were detected on the echocardiograms, compared with 17 (26%) of the 65 episodes without vegetations (P = 0.38). The mortality was 74% in patients with major neurologic manifestations and 56% in patients without neurologic manifestations (P = 0.008). In patients with neurologic complications the mortality was significantly higher among those treated with antibiotics alone as compared with those treated surgically (65 of 81, 80% versus 2 of 10, 20%; P = 0.0003). CONCLUSIONS: In a population of nondrug addicts with infective endocarditis caused by S aureus the following main conclusions can be drawn: neurologic manifestations occur with a higher frequency in patients with native mitral valve infection. The presence of vegetations on echocardiograms is not a risk factor for developing neurologic complications but this conclusion is based on the results of transthoracic echocardiograms performed in only one half of the patients. The majority of the neurologic manifestations occur on presentation or shortly thereafter and the risk of recurrent embolism is low. Mortality is increased in patients with neurologic manifestations. A neurologic event per se may constitute an indication for surgical treatment.

Adult↗
PubMed1997

Increasing frequency of vertebral osteomyelitis following Staphylococcus aureus bacteraemia in Denmark 1980-1990.

From 1980 to 1990, 309 cases of haematogenous osteomyelitis were identified in Denmark. Haematogenous osteomyelitis of the vertebral column increased significantly (P < 0.01) from the first to the second half of the period due to an increased number of patients > 50 years of age with community-acquired infection. Vertebral osteomyelitis differed significantly from osteomyelitis of other bones in accordance to age distribution (median 66 vs. 16 years), male/female ratio (75/71 vs. 105/ 58) and patients with diabetes (13% vs. 6%). We found a higher risk of haematogenous osteomyelitis in patients > 50 years of age and among patients with community-acquired infection. The highest incidence (5%) of vertebral osteomyelitis in Staphylococcus aureus bacteraemia in this age group was found in cases without an identified portal of entry. The highest incidence (34%) of osteomyelitis of other bones was found in community-acquired cases in the age group 1-20 years and without an identified portal of entry. The present study discusses reasons for the continued increase of vertebral osteomyelitis among adults and describes incidence rates and major risk factors for developing haematogenous osteomyelitis among patients with S. aureus bacteraemia. We suggest that the localization of haematogenous S. aureus osteomyelitis is connected with the presence of red bone marrow.

Adolescent↗
PubMed1997

Evaluation of different methods for the detection of methicillin resistance in coagulase-negative staphylococci.

The efficacy of 19 agar diffusion methods for the detection of methicillin resistance among coagulase-negative staphylococci (CoNS) within 24 h was evaluated. A total of 359 CoNS isolates were tested, of which 204 were Staphylococcus epidermidis. In 164 isolates, the presence of mecA was investigated; 61 strains were mecA-positive and 103 were mecA-negative by Southern blot analysis. Based on the best agreement shown with the mecA determination (94%) among four agar dilution assays for determining methicillin MIC, an assay with Columbia agar supplemented with NaCl and incubation with a heavy bacterial inoculum of 10(5)-10(6) cfu/spot was used as the reference MIC method. The best agar diffusion results were obtained with a 1 microg oxacillin disc on Columbia agar with 4.5% NaCl supplement. With this method, 99% of S. epidermidis and 94% of non-S. epidermidis were in agreement with the MIC determination. However, Columbia (without NaCl), Mueller-Hinton and Isosensitest agars were almost as useful when a 1 microg oxacillin disc was used. The zone breakpoints for S. epidermidis were, in general, considerably larger than those for other CoNS species and, consequently, differentiation according to species is recommended. Furthermore, resistance to other antibiotics, such as gentamicin and erythromycin, makes methicillin resistance highly likely.

Bacterial Proteins↗
PubMed1997

Comparison of the effect of cefepime with four cephalosporins against pneumococci with various susceptibilities to penicillin, in vitro and in the mouse peritonitis model.

The purpose of this study was to compare the effect, both in vitro and in vivo, of cefepime with those of four other cephalosporins, namely ceftriaxone, cefotaxime, cefuroxime and cephalothin, against penicillin-resistant pneumococci. One hundred pneumococcal strains, 31 penicillin-susceptible, 30 penicillin-intermediate-resistant and 39 penicillin-resistant pneumococci, were used in MIC studies. Time-kill experiments were carried out for four strains. In the mouse peritonitis model, the dose that gave protection to 50% of mice challenged with a lethal dose of pneumococci (ED50) was determined for three pneumococci and five cephalosporins. The MICs of all five cephalosporins and penicillin correlated significantly with each other. In vitro, the most potent cephalosporins against pneumococci were cefotaxime, ceftriaxone and cefepime, followed by cefuroxime and cephalothin. In time-kill experiments, carried out for four pneumococci, no differences were found in the killing effect of these five cephalosporins in relation to MICs. In the mouse peritonitis model, there was no significant correlation between log(MIC) and log(ED50) for the five cephalosporins against three pneumococci (Spearman's rho = 0.39, P = 0.16). However, if the values for cefepime against the three pneumococci were excluded, there was a significant correlation for the remaining four cephalosporins (Spearman's rho = 0.62, P = 0.04). For all three pneumococci, the ED50s of cefepime were lower than expected from the MICs. It was not possible to explain this beneficial difference in the effect of cefepime in terms of in-vitro bactericidal activities, serum protein binding or pharmacodynamic parameters.

Animals↗
PubMed1997

Coagulase and protein A polymorphisms do not contribute to persistence of nasal colonisation by Staphylococcus aureus.

The nasal carriage rate of Staphylococcus aureus was examined in a longitudinal study of 31 healthy Danish volunteers. Each person was classified as persistent (>8 positive cultures from 10 examinations), an intermittent carrier (50-80% positive cultures) or an ocassional carrier (positive cultures on 10-40% of ocassions only). One hundred and twenty strains from these persons were subjected to phage typing and random amplification of polymorphic DNA (RAPD) analysis. Phage and RAPD typing were in close agreement. RAPD confirmed the spread of a particular S. aureus clone (phage type 95) throughout Denmark. However, no common genotype or phenotype characteristics of S. aureus that could separate persistent from intermittent or incidental colonisers were identified. The immunoglobulin binding protein A and the prothrombin binding coagulase protein are both putative S. aureus virulence or defence factors. Analysis of polymorphisms in the variable repeat regions in the genes for these proteins showed no correlation between the number of repeat units and, consequently, the protein structure with the ability of strains to persist in the human nasal mucosa. The amount of protein A, detectable by its IgG binding activity, appeared not to be correlated to persistence of carriage. Thus protein A and coagulase gene polymorphisms do not seem to play a significant role in the propensity of S. aureus to colonise human nasal epithelium. Furthermore, based on the genetic heterogeneity encountered among the S. aureus strains it is suggested that within the current study population, no single clonal lineage of S. aureus has increased capability to colonise the human nasal epithelium.

Adult↗
PubMed1997

Antimicrobial susceptibility testing of 230 Helicobacter pylori strains: importance of medium, inoculum, and incubation time.

No standardized method of susceptibility testing for Helicobacter pylori is currently available, so before a large agar dilution study comprising 230 H. pylori strains belonging to more than 80 genetically different groups was initiated, we performed a relatively small preliminary study to determine the influences of medium, inoculum density, and incubation time. Seven media were investigated and were primarily evaluated on the basis of their abilities to support growth both semiquantitatively and qualitatively; Iso-Sensitest agar supplemented with 10% horse blood was found to be well suited for the purpose; this was closely followed by Mueller-Hinton agar with 10% horse blood, Mueller-Hinton with 10% sheep blood, and finally, 7% lysed horse blood agar. Investigations of two inoculum densities and two incubation times resulted in recommendations for the use of 10(9) CFU/ml (10[6] CFU/spot) as the inoculum and 72 h as the incubation time. A modest inoculum effect was noted for amoxicillin and metronidazole. By the methodology derived from our preliminary study, the susceptibilities of 230 H. pylori strains to six antibiotics were subsequently determined. The results were generally in accord with those of others, and apart from metronidazole, the MIC of which for approximately 25% of the strains tested was >8 microg/ml, resistance was low in Denmark. The situation might, however, quickly change when and if the number of indications for antibiotic therapy for H. pylori infections increase. Consequently, susceptibility testing of all H. pylori strains is recommended in order to survey the development of resistance, and in our hands the described methodology was relatively easy to perform and the results were easy to read.

Animals↗
PubMed1997

Activities of vancomycin and teicoplanin against penicillin-resistant pneumococci in vitro and in vivo and correlation to pharmacokinetic parameters in the mouse peritonitis model.

The activities of glycopeptides against pneumococci were studied in vitro and in vivo. The MICs of two glycopeptides, vancomycin and teicoplanin, in different media against 10 strains of pneumococci with different susceptibilities to penicillin were determined. The MICs of teicoplanin were four times lower than those of vancomycin in Mueller-Hinton media supplemented with 5% blood, but the MICs were similar in mouse and human sera supplemented with 5% blood. The serum protein binding levels in mouse and human sera were 90% for teicoplanin in both and 25 and 35%, respectively, for vancomycin. The MICs for vancomycin and teicoplanin were only correlated in human serum (P < 0.001). The single doses giving protection to 50% of the animals in the mouse peritonitis model after a lethal challenge of pneumococci, the ED50s, were similar for vancomycin and teicoplanin, between 0.1 and 1 mg/kg of body weight for all 10 strains. The log ED50s were significantly correlated only to the log MICs of teicoplanin determined for mouse serum with 5% blood (P = 0.01) and to the log MICs of vancomycin determined by the E test (P = 0.03). Among the pharmacokinetic parameters analyzed at the ED50s, the most constant parameter was the time for which the drug concentration exceeded the MIC (T(>MIC)) when each drug was considered separately; however, when both drugs were considered together, the maximum concentration of drug in serum (Cmax) varied the least. This indicates that both these parameters are of importance for predicting the effect of the drugs. We conclude that the effect of glycopeptides was not influenced by the penicillin resistance of the pneumococci, either in vitro or in vivo, and that the superior activity of teicoplanin over that of vancomycin in vitro was abolished in vivo, an effect which probably was due to the high serum protein binding of teicoplanin. Both the pharmacokinetic parameters T(>MIC) and Cmax are important predicting the effect of glycopeptides, but the pharmacodynamics of glycopeptides are still not completely elucidated.

Animals↗
PubMed1997

A study of 47 bacteremic Staphylococcus aureus endocarditis cases: 23 with native valves treated surgically and 24 with prosthetic valves.

A retrospective review of medical records from the Staphylococcus Laboratory, Copenhagen, 1982-1991, was carried out at the Department of Clinical Microbiology, Statens Serum Institut, 1994-1995, to investigate the clinical features and outcome of two subgroups of bacteremic Staphylococcus aureus endocarditis cases in non-drug addicts: patients with prosthetic valve endocarditis (PVE) and patients with native valve endocarditis treated surgically. Twenty-four cases of PVE were included. Six cases were early (within 60 days of valve implantation) and 18 were late. The overall in-hospital mortality was 42%. Surgical treatment resulted in a non-significantly lower mortality as compared with medical treatment alone (0% vs 50%, p = 0.19). Medical treatment of aortic and mitral valve endocarditis resulted in similar mortality rates (44% and 50%, respectively). Twenty-three cases of native valve infective endocarditis had the valve replaced surgically. The in-hospital mortality was 22%, which was significantly lower as compared with medical therapy (69%, p < 0.0001). The treatment changed significantly during the study period: 6 of 112 patients (5%) were treated surgically in the first half of the period (1982-1986) compared to 17 of 124 patients (14%) in the second half (1987-1991, p = 0.049). Severe congestive heart failure was the main indication for cardiac surgery in 21 patients. In conclusion, a shift towards a more aggressive surgical approach has taken place in the 10-year period. This development should be strengthened in the future as surgical intervention may improve survival in patients with infective endocarditis caused by S. aureus whether the infected valve is prosthetic or native.

Aged↗
PubMed1996

[Infections related to central venous catheters].

Central venous catheters (CVC) are a major source of nosocomial bacteraemia. The majority of cases are due to Staphylococcus aureus and coagulase-negative staphylococci. Severe complications, in particular septic shock, develop in 30% of all CVC-associated septicaemia cases and are usually caused by S. aureus. Some patients develop metastatic suppurative complications. Risk factors include prolonged catheterization, localization of catheter to the groin, the number of times the system is entered, use for parenteral nutrition and for dialysis, immunosuppresion and loss of skin integrity especially in burns. Important measures to decrease the rate of CVC-related infections include aseptic technique during insertion, changing transparent semipermeable dressing at least every 48 hours and replacement of the entire delivery system every 72 h. Technological advances such as bonding antimicrobial agents to the intravascular device may reduce the risk of infection. Treatment of CVC-related infections usually requires catheter removal.

Bacterial Infections↗
PubMed1996

Staphylococcus aureus carriage and infections among patients in four haemo- and peritoneal-dialysis centres in Denmark. The Danish Study Group of Peritonitis in Dialysis (DASPID).

A three-month prospective surveillance study was undertaken in four dialysis centres to establish the prevalence of Staphylococcus aureus carriage in a Danish population of patients on haemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD). General data such as sex, age, diagnosis, number of months in dialysis, hospital and ward were registered on a precoded form. Standardized nose and four skin swabs (axillae, groins, perineum) were performed on the first day of the survey. After one and two months, nose swabs were collected. Infections were registered and cultures were sent for phage-typing together with the S. aureus strains isolated from the swabs; 59.5% of HD patients and 51.2% of CAPD patients carried S. aureus. Permanent carriage was most frequent (P < 0.00009), primarily in the nose (44.0 and 34.9%, respectively in HD and CAPD). Skin carriage alone was rare (2.4 and 4.7%). Approximately one third (36.6 and 40.7%) of infections were caused by S. aureus. Although diabetics were not significantly more frequent carriers (60.5%) than non-diabetics (55.0%), the incidence of infection was much higher (26.3% vs. 10.3%, P = 0.004). In CAPD, peritonitis and tunnel/exit-site infections predominated (81.4%), often caused by S. aureus (34.8%). More than two thirds of the infections in HD patients were related to intravascular catheterization. The most serious infection was septicaemia, in all cases due to S. aureus. S aureus infections occurred significantly more frequently among carriers (P = 0.005), and more than half the patients were infected by the same or possibly the same strain as they carried in the nose or on skin. Different regimens for the elimination of S. aureus carriage in dialysis patients are discussed. A policy for risk assessment of patients should be developed, and the elimination of S. aureus carriage before dialysis should be encouraged. Controlled trials comparing the cost-effectiveness of recommended regimens to eliminate carriage in HD/CAPD patients are needed. Nose swabs are reliable indicators of carriage in dialysis patients.

Carrier State↗
PubMed1996

Retrograde contamination and practical handling of urine-meters: a comparison of three systems for the measurement of hourly diuresis in an experimental bladder-drainage model and in clinical use.

OBJECTIVE: To compare three different urine metering systems for their ability to prevent retrograde contamination in an in vitro model of a closed urinary drainage system and for qualities important to their practical handling in a clinical setting. PATIENTS, MATERIALS AND METHODS: Using three urine-meters (the Braun Ureofix 511, the Kendall Curity 4000 and the Unoplast Unometer 500) the in vitro model was constantly flushed with a solution of Mueller-Hinton broth diluted with saline. On the first day, the urine collecting bag was inoculated with 10(8) cells of Pseudomonas aeruginosa. The system was operated for 12 days with daily sampling of the model bladder to detect any contamination. After 12 days the experiment was stopped and sampling performed at various locations, including the urine-meter and the tubing. Nine of each type of urine-meter were tested, i.e. three in three different experiments. In the clinical study, 45 patients were randomized to each of the three urine-meters and the nurses attending them were asked to complete a questionnaire on the practical handling of the urine-meters. RESULTS: When the urine-meters was omitted from the model system, the 'bladder' became contaminated with the test bacteria within 3 days. None of the nine Unometer 500 systems became contaminated, compared with four of each of the other two systems (P < 0.05). In clinical use, the Unometer 500 and Ureofix 511 were easier to suspend and empty than was the Curity 4000. The Unometer 500 was significantly easier to handle when the collecting bag was emptied. CONCLUSION: Urine-meters can prevent retrograde contamination in a closed bladder-drainage model, but the degree of prevention depends upon the type of urine-meter. In daily practice, there were differences in the ease of suspension of the systems and in the emptying of the urine-meter and collecting bag.

Attitude of Health Personnel↗