125 patient records were examined.
Mean age 62.6±1.3 years, of which 56.0% were male (n=70). The ethnic distribution was comparable to the Singapore population distribution. 79.2% were from government subsidised wards (n=99). 54.4% were admitted under nephrology (n=68), followed by surgery (n=29, 23.2%). 49 (39.8%) were referred to the infectious disease team.
72.8% were not immunocompromised (n=91). 21 (16.8%) had active malignancy, 8 (6.4%) on chemotherapy and 14 (11.2%) were on long term steroids.
Majority were on dialysis due to diabetic renal disease (n=82, 65.6%), followed by glomerulonephritis (n=10, 8.0%), hypertensive renal disease (n=9, 7.2%) and sepsis-induced renal failure (n=4, 3.2%). 84.0% (n=104) had dialysis thrice-weekly, with 3 (2.4%) requiring CRRT and 8 (6.4%) requiring SLED. 4 patients (3.2%) were on peritoneal dialysis on admission and converted to haemodialysis during their inpatient stay.
Samples obtained were mainly from blood (n=73, 58.4%). About a quarter (n=34, 27.2%) were from wound swabs, a minority (n=19, 15.2%) were from urine cultures. About half (n=65, 52.0%) did not have any positive microbiological result. The most common bacteria cultured was Klebsiella pneumoniae (n=18, 14.4%), followed by Escherichia coli (n=14, 11.2%) Staphylococcus aureus (n=11, 8.8%), Pseudomonas aeruginosa (n = 10, 8.0%), Enterobacter cloacae (n=7, 5.6%) and Streptococcus pneumoniae (n=4, 3.2%). When cultured, bacteria were sensitive to meropenem by EUCAST (European Committee on Antimicrobial Susceptibility Testing) criteria.
Most common diagnosis was pneumonia (n=40, 32%), followed by skin and soft tissue infections (n=22, 17.6%).
Meropenem was largely used with a culture-guided curative intent, (n=78, 65%). Indications include bone and joint infections (n=5, 6.4%), bacteraemia (n=9, 11.5%), chest infection (n=23, 29.5%), intra-abdominal infection (n=4, 5.1%), line sepsis (n=2, 2.6%), skin and soft tissue infection (n=15, 19.2%), urinary tract infection (n=9, 11.5%) and sepsis with no source (n=11, 14.1%). In contrast, meropenem was used for suppression of chronic infections in 9 (7.9%) patients. Indications include bone and joint infections (n=2, 22.2%), bacteraemia (n=1, 1115%), intra-abdominal infection (n=1, 11.1%), skin and soft tissue infection (n=4, 44.4%), and sepsis with no source (n=1, 11.1%). 2 were on meropenem due to hypersensitivity to other narrow spectrum antibiotics. Mean duration of therapy on meropenem was 11.5±1.2 days, with 8 patients requiring more than 30 days of meropenem. The longest duration was a total of 109 days.
87.2% received daily dosing of meropenem (n=109, 87.2%). 8 (6.4%) patients received intermittent dosing of meropenem only, and 6 (4.8%) patients received both types of dosing regimens. All patients on intermittent dosing were on a thrice-weekly dosing regime. Dosing of meropenem varied, with 8 (57.1%) patients on 2g/2g/3g dosing, 3 (21.4%) on 2g/2g/2g, 2 (14.3%) on 1g/1g/1g and 1 (7.1%) on 1g/1g/2g. This variation of dosing was also seen in the daily dosing regime, with a range from 500mg once to twice daily, to 1g once to thrice daily. Comparison of variables amongst different meropenem dosing regime is described in Table 1.
59.2% did not have any intervention for source control (n=74). Indications for meropenem include bone and joint infections (n=1, 1.4%), bacteraemia (n=6, 8.1%), chest infection (n=32, 43.2%), intra-abdominal infection (n=3, 4.1%), line sepsis (n=2, 2.7%), skin and soft tissue infection (n=4, 5.4%), urinary tract infection (n=8, 10.8%) and sepsis with no source (n=18, 24.3%). Of those who received interventions, 9 (7.2%) had percutaneous drainage, 22 (17.6%) major surgery and 15 (12.0%) had minor surgical procedures. For those who received percutaneous drainage, indications for meropenem include chest infection (n=5, 55.6%), intra-abdominal infection (n=3, 33.3%) and skin and soft tissue infection (n=1, 11.1%). For those who received major surgery, indications for meropenem include bone and joint infections (n=7, 31.8%), bacteraemia (n=2, 9.1%), chest infection (n=1, 4.6%), intra-abdominal infection (n=1, 4.6%), skin and soft tissue infection (n=10, 45.5%) and sepsis with no source (n=1, 4.6%). For those who had minor surgical procedures, indications for meropenem include bone and joint infections (n=5, 33.3%), chest infection (n=1, 6.7%), intra-abdominal infection (n=1, 6.7%), skin and soft tissue infection (n=8, 53.3%).
Mean LOS in hospital was 36.6±3.6 days. 38 (69.6%) required ICU admission with a mean ICU LOS of 10.2±2.0 days. LOS was longer in the group with continuous meropenem (34.7±2.7 days verses 15.5±2.7 days), though antibiotic duration was shorter (8.7±0.6 days versus 23.4±6.2 days). This longer duration of antibiotics despite shorter LOS is possible as patients on intermittent meropenem dosing receive their doses outpatient at their dialysis centres.
94.4% (n=118) did not have any documented adverse events. 5 patients developed Clostridium difficile colitis, 1 developed allergic reactions and 1 acquired Carbapenem-resistant Enterobacteriaceae (CRE) positive on screening. 43 (34.4%) were readmitted within 30 days. 28 (22.4%) had relapses within the year. Mean total LOS within the year was 64.8±15.0 days. 35 (28%) died within 1 year of discharge. Of the 20 patients with known cause of death, 7 died from cardiac-related causes, 3 from ESRF and 10 from infection-related causes, mostly secondary to pneumonia.