The authors have declared that no competing interests exist.
Conceived and designed the experiments: AJR APS DMG JAS. Performed the experiments: MM EOT MN. Analyzed the data: AJR APS DMG MN JAS. Contributed reagents/materials/analysis tools: MM EOT MN. Wrote the paper: AJR APS DMG JAS.
The microbiology and epidemiology of UTI pathogens are largely unknown in Botswana, a high prevalence HIV setting. Using laboratory data from the largest referral hospital and a private hospital, we describe the major pathogens causing UTI and their antimicrobial resistance patterns.
This retrospective study examined antimicrobial susceptibility data for urine samples collected at Princess Marina Hospital (PMH), Bokamoso Private Hospital (BPH), or one of their affiliated outpatient clinics. A urine sample was included in our dataset if it demonstrated pure growth of a single organism and accompanying antimicrobial susceptibility and subject demographic data were available.
A total of 744 samples were included. Greater than 10% resistance was observed for amoxicillin, co-trimoxazole, amoxicillin-clavulanate, and ciprofloxacin. Resistance of
Data suggests that antimicrobial resistance has already emerged to most oral antibiotics, making empiric management of outpatient UTIs challenging
Urinary tract infections (UTI) are considered to be the most common bacterial infection, and it is estimated that they affect up to 150 million individuals annually
The introduction of antimicrobial therapy has led to profound improvements in the management of urinary tract infections; however antimicrobial resistance is a growing problem and a cause of major concern in many countries
Recent clinical guidelines emphasize the importance of knowing local patterns of susceptibility of coliforms to antimicrobial agents
Ethical approval was granted by the institutional review boards at the Botswana Ministry of Health, Princess Marina Hospital (PMH), Bokamoso Private Hospital (BPH) and the University of Pennsylvania. These IRBs also granted waivers of consent, as all data was retrospectively collected and deidentified on our data collection sheets to ensure patient confidentiality.
This was a retrospective study of antimicrobial susceptibility data for urine samples collected at PMH, BPH, or one of their affiliated outpatient clinics. PMH has 525 beds and is the main public tertiary-care hospital in Botswana’s capital city, Gaborone, while BPH has 200 beds and is a private primary, secondary and tertiary-care hospital also located in the capital. Affiliated clinics are located throughout the greater Gaborone area and serve a population of around 300,000 people.
For PMH, we reviewed laboratory records of urine specimens submitted for investigations from patients who presented between January 1, 2007 and December 31, 2009. Samples from BPH, which opened on January 11, 2010 were collected between January 11, 2010 and December 31, 2010. For both hospitals, we included urine samples for patients who were admitted to various inpatient wards, as well as patients who had samples collected at affiliated outpatient clinics. All samples were collected as part of routine patient care.
A urine sample was included in our dataset if it demonstrated growth of a single organism with accompanying antimicrobial susceptibility, and subject demographic data were available. For patients with more than one sample, we included only the first positive sample with susceptibility data. Samples were excluded from the dataset if there were duplicate samples with differing sensitivities, if there were duplicate samples listed under multiple years, or if samples grew multiple pathogens.
Urine microscopy, isolation, and identification of organisms were carried out as part of the routine procedures in the microbiology laboratories at PMH and BPH. Antimicrobial susceptibility testing was conducted at PMH via disc diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines
Additional data collected included patient age, sex, HIV status and clinical setting.
Analysis was performed using standard descriptive statistics and STATA version 11.1 (College Station, TX). Proportions of resistance were compared using Fisher’s exact and chi-squared tests and p<0.05 was deemed significant.
At PMH, 680 urine culture samples were evaluated for inclusion. Samples were not cultured if urinalysis was normal. Twenty-eight samples were excluded for the following reasons: a) duplicate samples with matching specimen and medical record numbers, but differing sensitivities (sample with most complete sensitivity data was included)
At BPH, 760 samples were evaluated for inclusion from BPH. We included a total of 92 samples, with the remainder excluded for either no growth of a single organism, or growth of multiple organisms. The low culture positivity rate at BPH vs PMH may be explained by the fact that specimens were often cultured at BPH without a prior microscopy or dip or despite a negative microscopy or dip. Seventy-three percent of eligible samples from BPH were from outpatient clinics.
Urine dipsticks, as well as urine microscopy, culture, and sensitivities, were carried out inconsistently at both institutions. Cultures at PMH were generally performed on samples with >10 white blood cells (WBC) per high power field (hpf) on microscopy; however, some had cultures performed if they were only positive on dipstick testing for blood, leukocyte esterase, or nitrites. Sometimes cultures were performed without prior microscopy or with normal microscopy.
Information on patient demographics is listed in
Princess Marina Hospital (n = 652) | Bokamoso Hospital (n = 92) | |||||
Inpatient | Outpatient |
|
Inpatient | Outpatient |
|
|
37 (26–56) | 28 (22–41) |
|
50 (36–62) | 36 (29–47) |
|
|
<18 yrs | 13% | 9% |
|
4% | 12% |
|
18–65 yrs | 70% | 85% |
|
80% | 76% |
|
>65 yrs | 17% | 7% |
|
16% | 12% |
|
|
||||||
Female | 57% | 68% |
|
72% | 70% |
|
Unknown | 1% | 3% |
|
0% | 0% |
|
|
||||||
Negative | 25% | 5% |
|
36% | 42% |
|
Positive | 20% | 8% |
|
36% | 6% |
|
Unknown | 55% | 87% |
|
28% | 52% |
|
Uropathogens from PMH and BPH are listed in
Princess Marina Hospital | Bokamoso Hospital | |||||
Inpatient (n = 276) | Outpatient (n = 376) |
|
Inpatient (n = 25) | Outpatient (n = 67) |
|
|
|
58% | 66% |
|
52% | 67% |
|
|
16% | 12% |
|
16% | 3% |
|
|
7% | 4% |
|
4% | 7% |
|
|
4% | 4% |
|
0 | 3% |
|
|
1% | 4% |
|
0 | 0 |
|
|
2% | 3% |
|
0 | 1% |
|
|
3% | 2% |
|
4% | 1% |
|
|
3% | 2% |
|
4% | 4% |
|
|
2% | 2% |
|
4% | 4% |
|
|
1% | 1% |
|
0 | 0 |
|
|
1% | 1% |
|
4% | 4% |
|
|
1% | 0 |
|
12% | 0 |
|
|
0 | 1% |
|
0 | 3% |
|
|
<1% | 0 |
|
0 | 0 |
|
At BPH, 10 isolates (11%) were found to produce ESBL. Six were
* *Less than 15 samples analyzed for these antimicrobials as noted: PMH-Outpatients (ciprofloxacin, ceftazidime).
* *Less than 15 samples analyzed for these antimicrobials as noted: BPH-Inpatients (all antibiotics), PMH-Outpatients (ciprofloxacin, ceftazidime), PMH-Inpatients (ciprofloxacin, ceftazidime).
Resistance patterns to nitrofurantoin, ceftazidime, and ciprofloxacin did not differ significantly based on setting (P>0.05). Overall resistance to nitrofurantoin was ten percent or lower in all settings. Twenty-five percent of
Data were not available for resistance patterns of first- or second-generation cephalosporins at PMH. There was no significant difference in resistance patterns for cefazolin or cefuroxime at BPH when comparing inpatient and outpatient settings (P>0.05). There was 18 percent resistance to both cefazolin and cefuroxime among
Sub-analyses also compared the differences in microbiology and antimicrobial susceptibilities between samples from pediatric (<18 years old) and adult populations. There were no significant differences in the pathogens causing UTI when comparing these populations. However, compared to those from adult patients,
We further explored the association between known HIV status, uropathogens, and antimicrobial resistance of E. coli isolates. HIV status had no significant impact on the uropathogens that caused UTI in any setting. However, HIV status was associated with a difference in the resistance of
Resistance of
Recent work in Nigeria has explored the association between HIV status and UTI
There were a number of limitations in our study that are intrinsic to a study with a retrospective design. Specifically, the diagnosis of UTI would have benefitted from consistent recording of a urine dipsticks, as well as urine microscopy, culture, and sensitivities. However, these were carried out inconsistently at both institutions and represent an opportunity to improve overall care. Additionally, there were inconsistencies in record keeping at PMH. Laboratory data were intermittently recorded in either paper logbooks or in electronic databases - therefore there are some missing data from our analyses that might have impacted our results. Missing data may also have affected our analysis of HIV status. Almost three-quarters of patients at PMH and nearly half of patients at BPH had an undocumented HIV status at the time their urine samples were sent and these samples could not be included in the HIV analysis. These limitations would be adequately addressed through improved prospective UTI surveillance strategies at both sites.
The epidemiology of UTIs in Botswana appears in general to be similar to that found in much of the world. HIV status did not seem to significantly impact the microbiology of UTIs in our context but did impact antimicrobial resistance to co-trimoxazole. Findings from this retrospective study suggest that antimicrobial resistance has already emerged to most oral agents. Greater than 10% resistance was observed for amoxicillin, co-trimoxazole, amoxicillin/clavulanate, and ciprofloxacin. This makes empiric management of outpatient UTIs challenging. Resistance of
Overall resistance to nitrofurantoin was low in all settings, suggesting that it could be used as empiric monotherapy for simple cystitis. Aminoglycosides are an appropriate alternative in the inpatient setting when there is not a concern regarding nephrotoxicity and when enteral therapy is not an option and bacteremia is not suspected.
A standardized approach to the diagnostic workup of patients with suspected UTI in these settings would likely improve overall care. In addition, improved record keeping and a prospective surveillance system are needed in these Botswana hospitals in order to facilitate regular surveillance of antibiotic resistance as these levels continue to change.
The authors thank the microbiology laboratory teams at both Princess Marina Hospital and Bokamoso Private Hospital. They also greatly appreciate the extensive assistance of the staff of the Botswana-UPenn Partnership with carrying out this project.