Antibiogram profile for Staphylococcus aureus and Coagulase-negative staphylococci isolates from pregnant women with asymptomatic bacteriuria in Nairobi, Kenya
Abstract
Background:
Urinary tract infection (UTI) is a heterogeneous disease, which can be divided into several types of infection, such as acute, uncomplicated bacterial pyelonephritis, complicated UTI, recurrent cystitis and asymptomatic bacteriuria. Urinary tract infection (UTI) is one of the most frequent types of bacterial infections. The main purpose of this study was to determinate the frequency of Staphylococcus aureus and Coagulase-negative staphylococci (CoNS) in urine obtained from pregnant women attending antenatal clinic and their antibiogram profile to antimicrobial agents.
Material & Methods: This was a cross-sectional study involving women attending antenatal clinic at selected clinics of Nairobi County. The women who met the inclusion criteria were included in the study. The midstream urine samples of these women were subjected to culture, and sensitivity. The antimicrobial susceptibility profile Staphylococcus aureus and (CoNS) strains was done using disc diffusion method according to Clinical and Laboratory Standards Institute (CLSI) criteria. They were subjected to 11 Kanamycin, Gentamycin, Chloramphenicol, Ampicillin, amoxicillin/clavulanate, Ceftazidine, Tetracycline, Cotrimoxazole, Ciprofloxacin, Cefotaxime and imipenem.
Result: During the study 219 urine samples found to have significant asymptomatic bacteriuria (ASB). In overall 42.9% of all bacterial isolates were Staphylococcus aureus and Coagulase-negative staphylococci (CoNS).
Conclusion: There was a high prevalence of Staphylococcus spp as etiological agents of ASB among pregnant women. Therefore, routine screening for gram positive bacteria as etiological agent of ASB should be considered.
Keyword: asymptomatic bacteriuria, Staphylococcus, pregnant women
Introduction
Urinary tract infection (UTI) is a heterogeneous disease, which can be divided into several types of infection, such as acute, uncomplicated bacterial pyelonephritis, complicated UTI, recurrent cystitis and asymptomatic bacteriuria. Urinary tract infection (UTI) is one of the most frequent types of bacterial infections(Nicolle, 2015a). Asymptomatic bacteriuria refers to the presence of bacteria in urine. It is a condition in which urine culture reveals a significant growth of pathogens that are greater than 105 bacteria/ml, but without the patient showing symptoms.
Staphylococcus aureus infections are increasing in pregnant and postpartum women. S. aureus has been reported to colonize the vagina in 4%–22% of pregnant women(Chen et al., 2006). The major causatives agents of UTIs are Escherichia coli and other Enterobacteriacae. Gram-positive bacteria may be easily overlooked due to limited culture-based assays typically utilized for urine in hospital microbiology laboratories. Some UTIs are polymicrobial in nature, often involving one or more Gram-positive bacteria (Kline and Lewis, 2016).While the uropathogenic agents vary depending upon age, sex, catheterization and hospitalization. The pathogens traditionally associated with UTI are changing many of their features due development of antimicrobial resistance. Therefore, complicated UTI has a more diverse etiology than uncomplicated UTI. However organisms that rarely cause disease in healthy patients can cause significant disease in hosts with anatomic, metabolic, or immunologic underlying conditions(Ronald, 2003). Pregnancy increases risks for urinary tract infection due to the dilatation of the ureters from week 6 of pregnancy to delivery. During pregnancy there is increased bladder volume and decreased bladder tone, along with decreased ureteral tone and increased urinary stasis. All these are factors that would increase the risk of development of infection(Nicolle, 2015b). Staphylococcus spp are not considered as typical uropathogen, although S aureus UTI is known to occur in patients with urinary catheters and is associated with the development of invasive infection in these patients. However there is an increasing trend where many studies report dominant etiological agents being either E.coli or S aureus (Turpin et al., 2007). S. aureus is a worldwide pathogen whose natural reservoir is human and causes severe community-associated infections of skin and soft-tissue (Nordmann and Naas, 2005).
Most asymptomatic ASB are caused by bacteria and can easily be treated by antibiotics. However there is increased development of microbial resistance to these antibiotics. Treatment of infections caused by S. aureus can be one of the trick experiences in clinical practice. S. aureus is known to acquire resistance to new drugs and continues to challenge attempts to clear them during treatment (Onanuga et al., 2005). The resistance of S. aureus isolates to commonly used antibiotics in different parts of the world has been widely reported. Assessment of resistant patterns of microbes to drugs has shown a rise in the incidence of microbial resistance to most prescribed antibiotics(Akortha and Ibadin, 2008).
Therefore this study is aimed at determining the prevalence of Staphylococci spp in ASB cases and also determines their antibiogram. Resistance to antimicrobial agents among gram positive cocci clinical isolates is higher than community isolates(Andrade et al., 2006). Emerging resistance bacterial strains and antimicrobial resistance rates among pathogens recovered from community-acquired urinary tract infections is on the rise. This is being experienced in different magnitude in different regions resulting into limited therapeutic options. This changes in microorganisms involved in ASB requires continuous and regular antimicrobial resistance surveillance in order to guide the treatment regimes to be instituted. Most studies on UTIs have concentrated on the antimicrobial resistance profile of Gram-negative enterobacteria especially E. coli which are known to be the most prevalent UTIs causative organism. While the resistance profile of isolated Gram-positive organisms such as S. aureus are left undone despite the increasing prevalent rate of this organism in UTIs and their role in antibiotic resistance.
Material and Methods.
Nairobi, Kenya’s capital city is a typical sub-Saharan Africa (SSA) urban centre characterized by population explosion with a current population of about 3.4 million in 2010. Majority of resident estimated at 60–70% of her population live in informal settlements (UNHABITAT, 2008, African Population and Health Research Center, 2002). The Nairobi county health clinics are distributed within the county and some cater for specialized needs like dental, skin and infectious conditions. Among the health clinics there are those that cater from antennal clinic and there after normal delivery. These are the ones we selected according their location in the informal settlement area which are known risk factor for asymptomatic bacteriuria. The clinics run antenatal clinics on daily basis and all complicated cases are referred to a specialized county hospital within Nairobi.
Study design
This was a cross-sectional study of pregnant women on their first the antenatal clinic of the Nairobi county health centres. A questionnaire was used to obtain information from the study participants. The information obtained consisted of identification number, age, phone number, educational qualification, marital status, parity, gestational age, and human immune virus status. The inclusion criteria involved the first visits of apparently healthy pregnant women attending clinic for first visit those who gave their informed consent to participate in the study. However, the women excluded from the study were those who had features of urinary tract infection, fever, had taken antibiotics within 2 weeks of the study, had medical chronic conditions (HIV) retroviral disease, and those who declined to consent despite adequate counselling.
All pregnant women at the antenatal clinic, who met the inclusion criteria, were counselled on how to collect midstream urine. This involved initial instructions by the female attending trained nurses and laboratory technicians. The laboratory technicians supervised the urine-sample collection. The first part of the urine was voided, and approximately 10–15 mL of midstream urine was collected in a sterile universal bottle, that had been correctly labelled and given to the patients. The urine samples in the sterile universal bottles were taken to the laboratory for processing within 1 hour. These samples were subjected to culture, and sensitivity according to standard. Microscopy was done at the clinic involved centrifugation of approximately 10 mL of urine sample in a tube at 1,500 rpm. The sediments were poured on a clean slide and observed under a microscope for casts, pus cells, and yeast cells. The remaining urine was sent to processing laboratory for culture Samples were cultured on air dried plates of Cysteine lactose electrolyte deficient agar (CLED) using a calibrated loop delivering 0.002ml of urine. Plates were incubated aerobically at 37OC overnight. Colony counts yielding bacterial growth of 105organism/ml or more of pure isolates were deemed significant. Contaminated urine usually has less than 104organism/ml and often contains more than one bacteria species (Cedric et al., 2005). Suspected bacterial species were characterised by colonial morphology, gram stain followed by microscopic examination, motility test and biochemical tests. Isolates were identified to species level using standard methods according to Clinical and Laboratory Standard Institute Guidelines (CLSI; 2005). Identification of gram positive cocci isolates was performed by Gram staining, catalase, manitol fermentation and coagulase tests was done to identify Staphylococcus and CoNs. Coagulase test was done using both slide and tube methods(Forbes et al., 2007; Mandell et al., 2010).
Antimicrobial susceptibility testing
To evaluate antimicrobial susceptibility of isolates, Kirby-Bauer’s Disk diffusion method was done according to Clinical Laboratory and Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards) (CLSI, 2006). The following antimicrobial agents were used in this study: Kanamycin, Gentamycin, Chloramphenicol, and Ampicillin, amoxicillin/clavulanate, Ceftazidine, Tetracycline, Cotrimoxazole, Ciprofloxacin, Cefotaxime and imipenem. Briefly, the bacterial suspensions were obtained from overnight cultures. The turbidity of each bacterial suspension was adjusted equivalent to a no. 0.5 McFarland standard and then inoculated on Mueller- Hinton agar (Oxoid, UK). Diameter of inhibition zones was measured after incubation at 35ºC for 18-24 hours, and data was reported as susceptible, intermediate, and resistant. Staphylococcus aureus ATCC 25923 was used as reference strains for susceptibility testing. Multiple Antibiotic Resistance (MAR) index value of all the strains was calculated. The MAR index applied to a single isolate is defined as a / b, where ‘a’ represents the number of antibiotics to which the isolate was resistant and ‘b’ represents the number of antibiotics to which the isolate was subjected. Data were analyzed using SPSS version 23 software.
Results
Type of bacteria isolates Frequency Percent
Staphylococci spp 94 42.9%
Escherichia coli 85 38.8%
Klebsiella spp 17 7.8%
Pseudomonas spp 6 2.7%
Protues spp 6 2.7%
Citrobacter 5 2.3%
Enterococcus 4 1.8%
Enterobacter 2 0.9%
Total 219 100.0%
A total of 219 women visiting the antenatal clinic for first visit were found to have significant asymptomatic bacteriuria. The age of the women ranged between 16 to 45years. Staphylococci spp were the most common isolates at 42.9% followed by Escherichia coli 38.8%, then Klebsiella (7.8%), Pseudomonas spp (2.7%), Protues spp (2.7%), Citrobacter (2.3%), Enterococcus (1.9%) and Enterobacter (0.9%) respectively as indicated in table1. The resistance and susceptibility pattern of gram positive isolates from positive asymptomatic bacteriuria is shown in table 2. Gram positive bacterial isolates showed a high resistance to ampicillin and cefotaxime ranging from 50% to 92.3%. Imipenem had the lowest resistance to all isolates ranging from 0% to 10.3% and most isolates were susceptible to imipenem ranging from 89.7% to 100%. The resistance to kanamycin was relative low ranging from 20.7%to 24.6% for staphylococci spp.
Table 1: Distributions of bacteria isolates from asymptomatic bacteriuria
Antibiotics Staph aureus Coagulase negative staph Enterococcus
n=65 n=29 n=4
Ampicillin R
S 60(92.3%)
2(3.1%) 22(75.9%)
4(13.8%) 2(50.0%)
0(0%)
Tetracycline
R
S 33(50.7%)
28(43.1%) 14(48.3%)
10(34.5%) 1(25.0%)
2(50.0%)
Chloramphenicol
R
S 21(32.3%)
42(64.6%) 6(20.7%)
23(79.3%) 0(0%)
2(100%)
Cotrimoxazole
R
S 37(56.9%)
27(41.5%) 22(75.9%)
5(17.2%) 3(75.0%)
1(25.0%)
Ciprofloxacin
R
S 24(36.9%)
41(63.1%) 12(41.4%)
17(58.6%) 2(50.0%)
2(50.0%)
Ceftazidime R
S 41(63.1%)
19(29.2%) 15(51.7%)
11(37.9%) 3(75.0%)
0(0%)
Gentamycin
R
S 17(26.2%)
48(73.8%) 10(34.5%)
19(65.5%) 2(50.0%)
1(25.0%)
Amocy/clavua R
S 37(56.9%)
28(43.1%) 12(41.4%)
17(58.6%) 2(50.0%)
2(50.0%)
Cefotaxime
R
S 61(93.8%)
0(0%) 25(86.2%)
0(0%) 3(75.0%)
0(0%)
Imipenem
R
S 4(6.2%)
60(92.3%) 3(10.3%)
26(89.7%) 0(0%)
4(100%)
Kanamycin R
S 16(24.6%)
45(69.2%) 6(20.7%)
20(67.0%) 3(75.0%)
0(0%)
Table 2: Antibiotic sensitivity pattern of gram positive isolates in asymptomatic bacteriuria
Multiple Antibiotic Resistance Index of staphylococci spp
About 100% of the isolates were resistant to at least two and more of the antibiotics used. The MAR index value ranged between 0.18 and 1.0. The predominant MAR index was 0.27 and 0.36% both at 18.1% frequency followed by 0.45% at 17.0%. seven isolates were resistant to 2 / 11 of antibiotics tested while 14 and 11 isolates were resistant to six and seven antibiotics respectively their MAR index – 0.54 and MAR index – 0.6. Four isolates were resistant to all the eleven antibiotics tested. The isolates expressed 58 different antibiotic resistant patterns. AMP –TET- COT- CIP was frequent antibiotic resistance pattern as a stand alone or with other antibiotics. The resistance pattern ranged from two antibiotics to eleven antibiotics. Twelve (13.3%) of the staphylococci spp isolates were resistant to more than seven antibiotic tested.
Number Antibiotics isolates are resistant to Frequency Percent MRI
2 7 7.4% 0.18
3 17 18.1% 0.27
4 17 18.1% 0.36
5 16 17.0% 0.45
6 14 14.9% 0.54
7 11 11.7% 0.6
8 4 4.3% 0.7
9 2 2.1% 0.8
10 2 2.1% 0.9
11 4 4.3% 1.0
Total 94 100.0%
Table 3: Number of antibiotics staphylococcal isolate was resistant to, frequency and multiple resistance indexes
MRI-Multiple resistance indexes
Discussions
Pregnancy increases risk of developing UTI however in many cases infection remains asymptomatic (Abdullah and Al-Moslih,2005). In this study, the prevalence of asymptomatic urinary tract infection among pregnant women attending antenatal clinic of Nairobi County antenatal clinics was found to be at 21.5%. This has been reported and discussed in a manuscript published by Pan Africa Medical Journal (Ayoyi et al., 2017). The bacteria isolated from urine cultures were Escherichia coli (38.8%) Staphylococcus aureus was (29.7%), Non coagulase Staphylococcus was (13.2%), Klebsiella spp was (7.8%), Pseudomonas spp was (2.7%), Protues spp was (2.7%), Citrobacter spp was (2.3%), Enterococcus spp was (1.9%) and Enterobacter spp was (0.9%) respectively. In overall staphylococcal spp were predominant isolates in this study at 42.9%. This was in agreement with a study done by Tadesse which reported prevalence of staphylococcal spp at 45.6% (Tadesse et al., 2014). The predominance of staphylococcal spp has also be reported by Rahimkhani in a study done in Iran that reported Staphylococcal spp at 36% (Rahimkhani et al., 2008). This also agreed with another study done in Nigeria which worked with patients with UTI symptoms reported staphylococci spp being predominant(Ekwealor et al., 2016). Although the condion of study were quite different from those of the current study, the significance of staphylococcal spp as an important uropathogen cannot be overlooked.
The prevalence proportion of staphylococci at 42.9% in this study and similar reports demonstrated by other studies (Ekwealor et al., 2016; Rahimkhani et al., 2008; Tadesse et al., 2014);is an indication that etiological agents for bacterial UTI are dynamic and change with different influencing factors. Gram-positive bacteria are a common cause of urinary tract infection (UTI), particularly among individuals who are elderly, pregnant, or who have other risk factors for UTI (Kline and Lewis, 2016). However urinary tract infections involving Gram-positive bacteria may be easily overlooked due to limited culture-based assays typically utilized for urine investigation in hospital microbiology laboratories(Kline and Lewis, 2016). Experimental studies have demonstrated that staphylococcal spp are cleared quickly from the bladder however they can co-infect patient with other organisms( Kline et al., 2010). There is also evidence that Gram-positive bacteria are important uropathogens in their own right (Mctaggart et al., 1990). However they are easily overlooked because they are missed by routine diagnostic methods (Domann et al., 2003)
Effective treatment of patients with UTIs generally relays on the identification of the type of organisms and the selection of an effective antibiotic agent to the organism in question. The pattern of antimicrobial resistance of bacteria producing UTI varies in different regions (Beyene and Tsegaye, 2011). Multidrug-resistant (MDR) was defined as resistance to at least two or more antibiotics (Beyene and Tsegaye, 2011; Esmaeili, 2005). Of 98 isolates tested all (100%) were MDR. In particular, seventeen (18.1%) of isolates were resistant to at least three drugs, another seventeen (18.1%) of isolates were resistant to at least four drugs and sixteen (17.0%) of the isolates were resistant to five drugs. The predominant resistance patterns among the isolates involved Ampicillin, tetracycline, and cotrimaxazole which were reported in 33(56.9%) of the patterns. This was with combination with other antibiotics. The isolates expressed 58 different antibiotic resistant patterns. The susceptibility profile of the isolated bacteria showed wide range of antibiotic resistance patterns.
The data from our investigation exhibited varying antibiotic susceptibility profile with a significant resistance of more than 50% reported for staphylococcus spp isolates to ampicillin, tetracycline, cotrimaxazole, cefttazidime and cefataxime. In our study the susceptibility of staphylococcus spp to chloramphenicol, ciprofloxacin, gentamycin imipenem and kanamycin ranged from 63.1% to 92.3%. This agreed with other studies done earlier which reported high sensitivity to these antibiotics (Khoshbakht et al., 2012; Kumar et al., 2014). The possible reason for the steady increase in resistance to these antibiotics could be due sustained selective pressure due to their widespread use. A significant increase in resistance of bacteria causing UTI to, Ampicillin, cephalosporins and Sulfamethoxazole-trimethoprim has reported worldwide(Gupta et al., 2001). A high incidence of MDR strains was reported in this study. It could be attributable to high usage of antimicrobials agents in the community. Continued use of antibiotic for treatment of UTI and other infection should be monitored to prevent the spread of resistant isolates and also minimize the use of antibiotics for a prolonged period(Mansour et al., 2009).
Gram positive bacterial isolates showed a high resistance to ampicillin and cefotaxime ranging from 50% to 92.3%. Imipenem had the lowest resistance to all isolates ranging from 0% to 10.3% and most isolates were susceptible to imipenem ranging from 89.7% to 100%. The resistance to kanamycin was relative low ranging from 20.7%to 24.6% for staphylococci spp. Staphylococcal spp showed high resistance to ampicillin and cefotaxime while kanamycin and Imipenem reported a relatively higher sensitivity to the bacterial isolates. Twelve (13.3%) of the staphylococci isolates were resistant to more than seven antibiotic tested. This agreed with studies that have demonstrated staphylococci being resistant to penicillins, carbapenems and beta-lactam/beta-lactamase inhibitor combinations (Clinical Laboratory Standards Institute., 2015). Recently, several studies have shown that the methicillin-resistant staphylococci have started to gain resistance to many widely used antibiotics quinolone, macrolide, amino glycosides, tetracycline, trimethoprim-sulphamethoxazole and chloramphenicol (Knauer et al, 2004). This study did not report the methicillin-resistant staphylococci however the resistance patterns reported in this study relate closely those reported earlier.
Carbapenems are broad-spectrum antibiotics with activity against both Gram-positive organisms and Gram-negative organisms. Seven isolates reported resistance to imipenem which is a carbapenem and they are used as last line antibiotics. Despite introduction of antimicrobial agents and medical improvements in controlling staphylococci infections, they have remained important hospital and community pathogen (Anuniti et al., 2016). Furthermore, these bacteria have become a major concern to the medical community due to their extraordinary ability to adapt rapidly to antibiotic stress(Livermore, 2000). Although resistance to imipenem and Kanamycin has been reported among our isolates, however the level of reported was relative low therefore they can be effective drugs for treatment of UTI associated with gram positive cocci. According to our findings, Ampicillin, Cefotaxime, ceftazidime and Sulfamethoxazole-trimethoprim are not effective drugs for treatment of UTI. Progressive increase in resistance to these antibiotics and multiple resistances to antibiotics in present study may be related to increased usage of these antibiotics for treatment of UTI and ability of bacterial strains in acquisition of resistance genes.
The MAR index value reported ranged between 0.18 and 1.0. The predominant MAR index was 0.27 and 0.36% both at 18.1% frequency followed by 0.45% at 17.0%. seven isolates were resistant to 2 / 11 of antibiotics tested while 14 and 11 isolates were resistant to six and seven antibiotics respectively their MAR index – 0.54 and MAR index – 0.6. Others gave higher MARI. MARI is a tool that reveals the spread of bacteria resistance in a given population (Ugwu et al., 2009). Any MARI greater than 0.20 implies that the strains of such bacteria originate from an environment where several antibiotics are used (Ehinmidu, 2003; Tambekar et al., 2006, 2006); (Oli et al., 2013). In this study MRI ≥ 0.2 was expressed by 92.5% of the isolates. This implies that a very large proportion of the bacterial isolates have been exposed to several antibiotics and thus has developed resistance to these antibiotics. Similar incidence was reported in the work of Ehinmidu (Ehinmidu, 2003). A similar reported was demonstrated by Prakash and Saxena (Prakash and Saxena, 2013). The high MARI from urine samples isolates in this locality emphasizes the need for continuous monitoring of antibiotic susceptibility profile of bacteria implicated in UTI prior to antibiotic prescription.
Conclusion
The high level of resistance among gram positive bacteria causing UTI limits the use of antimicrobial agents for therapy and also the spread of MDR isolates is a threat for hospitalized patients. Continuous Surveillance for multidrug-resistant strains is necessary to prevent the further spread of resistant isolates
Acknowledgements
The authors would like to thank the staff of all attending Nurses and laboratory scientists from Kangemi, Kahawa and Riruta health centers for their role in evaluation of subjects and collection of samples. The urine microscopy was done at clinics and was done by laboratory scientists. This study was funded by National Commission for Science Technology and Innovation-Kenya.
Conflict of interest
The authors declare that they have no conflict of interests.
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