Bacteraemia in Maiduguri Metropolis, Nigeria: A 2005 to 2009 study of some causative pathogens and fluoroquinolones activities against them

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1 ISSN: Received o: Revised o: Accepted o: Bacteraemia i Maiduguri Metropolis, Nigeria: A 2005 to 2009 study of some causative pathoges ad fluoroquioloes activities agaist them Ohieku Joh David, Rilwau Amiu Magaji ad Duru Christia ABSTRACT Ohieku Joh David, Rilwau Amiu Magaji Departmet of Cliical Pharmacy ad Pharmacy Admiistratio, Faculty of Pharmacy, Uiversity of Maiduguri, PMB 1069, Maiduguri, Boro State, Nigeria Duru Christia Departmet of Microbiology, Uiversity of Maiduguri Teachig Hospital, Maiduguri, Boro State, Nigeria Blood-stream pathoges were ivestigated betwee 2005 ad 2009 i 262 patiets with septicaemia i Maiduguri Metropolis, Nigeria to evaluate treds i fluoroquioloes activities agaist them. Blood samples were cultured i a eriched utriet agar while susceptibilities tests were performed usig the disc diffusio techiques.staphylococcus aureus, the predomiat pathoge accouted for 57.6% ad peakig i 2007 with 26.5%. Salmoella spp (overall: 20.2%) ifectivity icreased from by 15% but Klebsiella bacteraemia (14.9%) decreased by 20.7% from Bacteraemia caused by Escherichia coli (7.3%) was the least. The S. aureus sesitivity to ciprofloxaci decreased by 25% betwee 2005 ad 2007 while ofloxaci steady decrease from 2005 to 2008 by 33% showed sigificat correlatio (P<0.05). Ciprofloxaci activities agaist orfloxaci-resistat ad pefloxaci-resistat S. aureus (74.5% ad 75% respectively) are both sigificatly differet (P<0.005) from ofloxaci (27.7% ad 37.5% respectively) but 92%, 81% ad 78% of alidixic -resistat Klebsiella spp are sesitive to ciprofloxaci, ofloxaci ad pefloxaci respectively. The ofloxaci s activities agaist E. coli were superior to ciprofloxaci with 50%, 69% ad 94% of alidixic -resistat E. coli beig sesitive to pefloxaci, ciprofloxaci ad ofloxaci respectively. However all ciprofloxaci-resistat E. coli are ofloxaci-sesitive. The study foud occurrece of cotiuous ad sigificat loss i activities of most fluoroquioloes agaist S. aureus ad E. coli but while ciprofloxaci idicated high activities agaist S. aureus ad Klebsiella bacteraemia, ofloxaci was superior agaist E. coli ad Salmoella bacteaemia tha other agets. Key words: Bacteraemia, ciprofloxaci, fluoroquioloes, Staphylococcus aureus, Pathoges, alidixic- resistat. INTRODUCTION For Correspodece: OHIEKU, Joh David joi.da.v@hotmail.co.uk Tel: Followig their itroductio as chemotherapeutic agets agaist ifectious diseases, the fluoroquioloes empiric choices have gaied prefereces over most other previously itroduced atibiotic agets i may regios (Hooper, 2000). They have become oe of the fastest growig atibacterial classes i terms of global reveue ad are icreasigly beig used i both hospital ad commuity sectors (Bhaot et al., 2001). Their uses was reported to have icreased by threefold i the emergecy room eviromet betwee 1995 ad 2002 i the US (MacDougall et al., 2005) ad have become first lie treatmet i some serious cases requirig patiet hospitalizatio (Liu ad Mulhollad, 2005). Most pathoges isolated from various ifectious sites were reported to show low levels resistaces o the average compare to other existig agets (Ohieku et al., 2010). The ability to add several substituet groups at various sites of the alidixic moiety does ot oly cofer higher activities ad potecies agaist may pathoges (Saeed et al., 2005) but have also led to several cogeers makig them oe of the abudat class of agets

2 Itroduced ito the pharmaceutical market i recet times (Saeed et al., 2005). They have wide spectra of activities especially agaist Neisseria Spp, Haemophillus ifluezae, Morexella catarrhalis, Mycoplasma, Chlamydia spp, Chlamydophila spp, Regioella spp, Eterobacteriaceae, Pseudomoas aerugiosa (particularly ciprofloxaci), Mycobacterium tuberculosis, some atypical mycobacteria, ad Methicilli-sesitive Staphylococci (The Merck, 2009) thereby expadig their applicatios i cliical practice. Newer agets like levofloxaci, moxifloxaci ad gatifloxaci have exteded activities agaist Gram positive pathoges (Duggirala et al., 2007) while may other fluoroquioloes are developed havig activities agaist some aaerobes (David, 2010). Their pharmacokietics properties which favor oce or twice daily admiistratio have made it coveiet ad acceptable to patiets ad therefore justifyig their empirical choices ad recommedatios (Hooper, 2000). All these advatages offer the cliicias with the privilege of choosig from a wide rage of agets with similar profile or mior variatio i their pharmacological profiles. However, the idiscrimiate uses of the fluoroquioloes for mior coditios have geerated cocer i several regios because of chaces of resistace developmet. Resistaces to them is capable of evolvig rapidly, eve durig the course of treatmet ad may strais of Staphylococcus aureus, eterococci, Streptococcus pyogees ow exhibited resistaces worldwide (Jacobs, 2005). Specifically, resistaces to the older geeratio fluoroquioloes like ciprofloxaci, orfloxaci, pefloxaci ad ofloxaci with Eterobacteriaceae, Neisseria, Pseudomoas aerugiosa, S. peumoia are growig due to their icreasig uses (The Merck, 2009). Although oe of the special abilities of bacteria i spreadig resistaces is their capacity to exchage resistace gees (plasmid) amog similar ad dissimilar groups, may other factors like epidemiologic, local atibiotics policies, patiet s characteristics, origi of strais, geographical locatios are amog the factors cosidered to have icreased the resistace rate of the Fluoroquioloes (Acar ad Goldstei, 1997). Resistace problems are associated with life-threateig cases ad death. Accordig to the Ceter for Disease Cotrol (CDC) report i 2005, about life-threateig ifectios ad deaths were reported i the US i 2005 from methicilliresistat Staphylococcus aureus (MRSA) ifectio (Saly, 2007). The Exteded spectrum beta-lactamases (ESBLs) pathoges; which are mostly Klebsiella spp ad E. coli with the icideces foud with most Eterobacteriacea (Keeth, 2008) are similarly healthcare problems. Cocers have grow over the years with problems like MRSA icludig those of hospital-acquired ad commuity-acquired MRSA, vacomyci-resistat Staphylococcus aureus (VRSA), vacomyci-resistat eterococci (VRE) ad ESBL which are resistat to cephalosporis ad moobactams, ad peicilli-resistat Streptococcus peumoiae (PRSP). Bacteraemia is a coditio with high mortality rate ad where quick itervetios with atibiotics therapy havig high activities such as the fluoroquioloes are required. However, the icreasig multi-drug resistat pathoges have caused therapeutic problems i may regios. There are worries that the fluoroquioloes which have become first lie agets may have created circumstaces that icrease resistaces of pathoges i the regio due to their cotiuous ad idiscrimiate use sice resistaces are ofte associated with previous overuse ad misuse of ay aget (Austi et al., 1999). We isolated ad studied the ivitro sesitivities of pathoges icrimiated i bacteraemia to the fluoroquioloes commoly used i the regio from i patiets diagosed with bacteraemic ifectios ad ivestigated their resistat status ad their iter-activities relatioships to some pathoges. AIMS AND OBJECTIVES The study aimed at ivestigatig treds i bacteraemic pathoges i the regio, the activities of the fluoroquioloes agaist blood-stream bacterial isolates ad to ivestigate the iteractivities relatios of these atibiotics. MATERIALS AND METHODS Samplig 262 cases of blood-stream bacterial ifectios were ivestigated betwee 2005 ad 2009 i idividuals suspected to have septicaemia followig the preseted cliical sigs ad symptoms ad cofirmed with microbiological blood-stream assay. Blood Culture ad Sesitivity Assay The idividual blood sample was cultured i a eriched utriets agar icubated at 37 o C for 7 days. Biochemical tests were further carried out to characterize the isolated pathoges. All pathoges are judged cliically sigificat from the microbiological reports. Susceptibilities tests were performed usig the disc diffusio techiques ad tested agaist the disc cocetratios of ciprofloxaci (30 µg), pefloxaci (10 µg), ofloxaci (10 µg), orfloxaci (30 µg) ad alidixic (30 µg). Statistical Aalysis Chi square aalysis was used to determie levels of activities betwee two or more agets at 95% cofidece iterval. RESULTS AND DISCUSSION The blood is though a sterile zoe; but bacteria ca gai access to it through may routes to cause bacteraemia. The distributio of pathoges isolated from the blood stream of patiets with bacteraemia (Table 1) idicated a geeral icrease i icidece by 6.1% betwee 2006 ad Staphylococcus aureus (57.6%), was the oly ecoutered gram-positive bacteria with its ifectivity peakig i The Salmoella spp bacteraemic ifectivity icreased from by about 15% peakig i 2008 but showed o correlatio betwee levels of isolates durig these periods. The decrease i Klebsiella spp bacteraemic icideces betwee 2006 ad 2008 recorded sigificat correlatio (P<0.01) as the year icreased. Escherichia coli blood ifectios was cosistetly lower tha other pathoges but its recorded

3 icrease betwee 2007 ad 2009 (26.8%) was ot foud to be sigificat (Table 1). Table 1: Isolated pathoges i blood-streams of patiets betwee 2005 ad Pathoges Frequecy of bacterial isolates TOTAL S. aureus 30 (19.9%) 23 (15.2%) 40 (26.5%) 19 (12.9%) 39 (25.8%) 151 (57.6%) Salmoella spp 9 (17%) 8 (15.1%) 11 (20.8%) 13 (24.5%) 12 (22.6%) 53 (20.2%) Klebsiella spp 6 (15.4%) 13 (33.3%) 9 (23.15) 5 (12.8%) 6 (15.4%) 39 (14.9%) E. coli 3 (15.8%) 4 (21.1%) 2 (10.5%) 3 (15.8) 7 (36.8%) 19 (7.3%) TOTAL 48 (18.3%) 48 (18.3%) 62 (23.7%) 40 (15.3%) 64 (24.4%) 262 (100%) Although there are may possible risk factors for S. aureus ifectios (Marwick et al., 2007; Keeth, 2008), this high icidece is ot surprisig sice high resistace rates of S. aureus isolates from may ifectious sites to may classes of atibiotics i the regio were previously reported (Ohieku et al., 2010) cotributig to icreasig hospital visits. The result is i agreemet with other authors who reported S. aureus as oe of the predomiat pathoges causig bacteraemia (Eabulele et al., 2008) but is i cotrast to what was reported i Eglad betwee 2004 ad 2008 where E.coli (23%) was the most commo bacteraemic pathoge followed by S. aureus (Wilso et al., 2008). I Gambia, the 18.3% reported icidece of S. aureus was secod to Streptococcus peumoiae ad lower tha our result while E.coli bacteraemic isolates was a little higher tha obtaied i our result (Hill et al., 2007). Kha ad Associates (2010) reported i Qatar that E. coli blood isolates (21.5%) was the predomiat pathoge but bacteraemia caused by E. coli (7%) i Keya (Thomas et al., 2009) showed similar proportio with our fidigs (7.3%). Although there was a icrease i E. coli ifectivity by 26.3% betwee 2007 ad 2009 but the recorded overall icidece is lower tha the 27% of E. coli bacteraemic cases reported i Spai (Ortega et al., 2009). The reaso for these differeces is attributable to variatio i eviromet ad health-care practice icludig variatio i atibiotic resistace sice atibiotics may have bee misuse for several extra-vascular ifectios before pathoge gai access to the blood stream. These icreasig treds i bacteraemia caused by S. aureus ad other pathoges are worrisome whe compared with the decliig icidece of S. aureus associated bacteraemia reported i some regios i Eglad durig similar period (Wilso et al., 2010). There is therefore the eed to focus attetio to curtail these rises. The overall gram-egative bacteraemia recorded is 42.4% but the Klebsiella bacteraemia icidece recorded i this study is slightly lower tha the 15.5% previously reported i the regio (Ohieku et al., 2010). The higher rate of gram-positive icidece (57.6%) over gram-egative bacteraemia (42.4%) i the study showed similar treds with the 58.5% ad 38.5% respectively reported i Greece (Starakis et al., 2010) but were i cotrast to lower treds reported i Israel (Marchaim et al., 2008). Geerally, gram-positive bacteraemia are icreasig i may regios (Potecelli, 2008). Similarly, Salmoella bacteraemia icreases by 9.4% betwee 2006 ad 2008 i our study due to evirometal exposure ad food-bore coditios as equally reported i some regios (Timothy et al., 2006). All these variatios are aturally associated with may factors icludig those of epidemiologic, local atibiotics policies, patiet s characteristics, idividual ad evirometal hygiee, ad geographical locatios. The susceptibility treds of blood-stream bacteria to the quioloes from 2005 to 2009 are show i Table 2. Table 2: Quioloes activities agaist isolated blood-stream pathoges betwee 2005 ad Atibiotics Quioloes Percetage activities agaist Staph aureus Quioloes Percetage activities agaist Salmoella spp Ciprofloxaci Ofloxaci Pefloxaci Norfloxaci Table 3: Compariso of activities of Quioloes to resistat bacteraemic Staph aureus. Nos (%) of Resistace Staph aureus that are sesitive to No. of Staph aureus other quioloes Resistace to Nal. Norfloxaci Pefloxaci Ciprofloxaci Ofloxaci (=5) XXX 0 5 (100) 4 (80) 5 (100) Norfloxaci (=47) 0 XXX 8 (17.0) 35 (74.5) 13 (27.7) Pefloxaci (=8) 0 2 (25) XXX 6 (75) 3 (37.5) Ciprofloxaci(=20) 1 (5) 5 (25) 5 (25) XXX 6 (30) Ofloxaci (=11) 1(9.1) 1 (9.1) 2 (18.2) 6 (54.5) XXX S. aureus sesitivity to ciprofloxaci decreased by 19% betwee 2005 ad 2006 ad by further 6% i 2007, but these decreases are ot sigificat (P>0.050) ad o resistaces were recorded i 2008 with all the pathoges. The ofloxaci activities agaist S. aureus which recorded steady declie betwee 2005 ad 2008 idicated sigificat correlatio as the year icreases (P<0.05). This sesitivity treds recorded with ofloxaci i 2008 is similar to the reported i Easter part of Nigeria (Ikeogwu et al., 2008). Activities of pefloxaci agaist S. aureus similarly decreased from 2007 to 2009 by similar margi ad are attributed to variatio i previous utilizatio rates although cross resistace may be cotributory. The Ciprofloxaci s high activities agaist orfloxaciresistat S. aureus (74.5%) compare to ofloxaci (27.7%) (Table 3) idicated sigificat differece (P<0.005) betwee the two agets. Similarly, ciprofloxaci activities (75%) were higher tha ofloxaci (37.5%) amog pefloxaci-resistat S. aureus bacteraemia though the reverse was the case with alidixic resistat S. aureus cases (Table 3). Oly 30% of ciprofloxaciresistat S. aureus were sesitive to ofloxaci whereas 54.5% of ofloxaci-resistat S. aureus are sesitive to ciprofloxaci. All the alidixic -resistat S. aureus are sesitive to ofloxaci. Although the resistaces of Staphylococcus aureus to the fluoroquioloes are reported worldwide (Jacobs, 2005) with ewer geeratio fluoroquioloes demostratig higher activities tha these older oes (Joh et al., 2008), but the geeral, rapid declie i sesitivity patters of S. aureus recorded with all the

4 fluoroquioloes compare to other pathoges i this study (Table 2) is worrisome. These results demostrated that some strais of S. aureus utreatable with the available fluoroquioloes i the zoe have emerged. Ciprofloxaci however appeared to be the treatmet optio for most quioloe-resistat S. aureus bacteraemia while there is a urget eed to itroduce other agets i order to resolve resistace strais i the regio. May practice fields have eacted guidelies regardig the fluoroquioloes utilizatio to safeguard the cotiuous resistace agaist them. For example, agets like the macrolides or doxycyclies are recommeded as first lie rather tha the fluoroquioloes by the America Thoracic Associatio (Wikipedia, 2011). Similarly the drug resistat Streptococcus peumoiae Workig Group recommeds that fluoroquioloes be used oly after other atibiotics have bee tried ad failed while others have made recommeded itervetios to reduce their excessive prescriptio i the U.S. (MacDougall et al., 2005). It is hopeful that appropriate atibiotic policy i the regio will be of immese therapeutic beefit. Ciprofloxaci, ofloxaci ad pefloxaci activities agaist Salmoella spp are high ad almost uiform (Table 2). The pathoge recorded o resistaces to ofloxaci ad the decrease i activities of ciprofloxaci i 2006 ad pefloxaci i 2008 were ot foud to be sigificat. The activities of these drugs do ot vary sigificatly from their previously reported status i the regio (Ohieku et al., 2010). All the strais of Salmoella spp isolates i 2005 ad 2006 were resistat to alidixic but about 92% activities each were recorded by ciprofloxaci ad pefloxaci agaist alidixic -resistat Salmoella bacteraemia while 100% were recorded with ofloxaci (Table 4). Table 4: Compariso of activities of Quioloes to resistat bacteraemic Salmoella spp. No. of Salmoella No. (%) of Resistace Salmoella spp that are sesitive to other spp resistace to quioloes Nal. Norfloxaci Pefloxaci Ciprofloxaci Ofloxaci XXX 0 24(92.3) 24 (92.3) 26 (100) (=26) Norfloxaci (=1) 0 XXX 0 1 (100) 0 Pefloxaci 0 0 XXX 0 0 Ciprofloxaci(=1) 1 (100) 0 1 (100) XXX 1(100) Ofloxaci (=0) XXX The study foud these three agets still relevat i bacteraemia coditios caused by Salmoella pathoges i the regios suggestig that they may have a high cure rate agaist typhoid fever ad other o-typhoidal or Salmoellosis diseases i the regio. Our result cofirmed the report that Salmoella spp whether alidixic -sesitive or alidixic -resistat are usually sesitive to most fluoroquioloes (Asperilla et al., 1990). Ciprofloxaci s activities agaist Klebsiella spp showed o observable resistace durig the period except i 2006 (Table 5). These recorded activities are better whe compared with higher resistace rates recorded by the pathoge i Eglad, Wales ad North Irelad betwee 2005 ad 2009 (Health Protectio Report, 2010). The ciprofloxaci activities agaist Klebsiella spp were cosistetly higher tha ofloxaci except i 2006 (Table 5) suggestig that it is the treatmet optio where empiric choices are required. Table 5: Quioloes activities agaist isolated blood-stream pathoges betwee 2005 ad Atibiotics Quioloes Percetage activities agaist Klebsiella spp Quioloes percetage activities agaist E. coli Ciprofloxaci Ofloxaci Pefloxaci Norfloxaci This fidig is i agreemet with that of Duggirala ad colleagues (2007) where superior activities of ciprofloxaci over ofloxaci agaist gram egative pathoges was reported, but is i cotrast to the work of Joes ad colleagues (1992) who reported ofloxaci s high activities agaist Klebsiella spp for may years. The variatio i their utilizatio from oe regio to aother ad the level of adopted atibiotics policies may cotribute to these observed differeces. However, Klebsiella spp appeared to have recorded a improved sesitivity to pefloxaci betwee 2005 ad 2008 (Table 5). These icreases however, showed o correlatio durig the study periods (P>0.05) but there was a overall icrease i resistace of this pathoge over the previous report (Ohieku et al., 2010). 91%, 83% ad 78% of alidixic -resistat Klebsiella bacteraemia were sesitive to ciprofloxaci, ofloxaci ad pefloxaci respectively (Table 6). Table 6: Compariso of activities of Quioloes to resistat bacteraemic Klebsiella spp. No. of Klebsiella spp Resistace to Nos (%) of Resistace Klebsiella spp that are sesitive to other quioloes Nal. Norfloxaci Pefloxaci Ciprofloxaci Ofloxaci 0 18 (78,3) 21(91.3) 19(82.6) (=23) XX X Norfloxaci (=1) 0 XXX 1(100) 0 0 Pefloxaci (=6) 0 0 XXX 5 (83.3) 5 (83.3) Ciprofloxaci(= XXX 1(100) ) Ofloxaci (=5) 2 (40) 0 5 (100) 5 (100) XXX Surprisigly, ofloxaci activities agaist E. coli, aother gram egative pathoge were superior to ciprofloxaci though uiform activities were recorded by both agets i 2008 (Table 5). The higher resistat rates of E. coli to ciprofloxaci are i agreemet with the work of Starakis ad colleagues (2010) i Greece ad is attributable to the higher utilizatio rate of ciprofloxaci over ofloxaci i the regio though acquire resistace to the fluoroquioloes or other classes of atimicrobial agets may play a role (Weier et al., 1999). The 17% loss i activities of ciprofloxaci i the study is lower tha the 22% of ciprofloxaci-resistat cases reported by Blazquez ad colleagues (2002) i Spai. The pefloxaci activities agaist E. coli were cosistetly lower tha its activities agaist other pathoges durig the year

5 except i 2005 ad are also lower tha that of other fluoroquioloes except i 2008 (Tables 2 ad 5). However, 50%, 69% ad 94% of alidixic -resistat E. coli were sesitive to pefloxaci, ciprofloxaci ad ofloxaci respectively (Table 7). Similarly 37.5% ad 87.5% of pefloxaci-resistat E. coli bacteraemic pathoges were sesitive to ciprofloxaci ad ofloxaci respectively while all the ciprofloxaci-resistat E. coli bacteraemic isolates were sesitive to ofloxai (Table 7) thus makig ofloxaci the treatmet optio agaist E. coli bacteraemia i the regio. 11.4% of ciprofloxaci-resistat E. coli bacteraemia were reported i Korea (Chug et al., 1999). Table 7: Compariso of activities of Quioloes to resistat bacteraemic Escherichia coli. No. of E, coli Resistace to No. (%) of Resistace Escherichia coli that are sesitive to other quioloes Nal. Norfloxaci Pefloxaci Ciprofloxaci Ofloxaci (=16) XXX 0 8 (50) 11(68.8) 15 (93.7) Norfloxaci 0 XXX 0 0 Pefloxaci (=8) 0 0 XXX 3 (37.5) 7 (87.5) Ciprofloxaci(=5) XXX 5 (100) Ofloxaci (=1) (100) XXX CONCLUSION Our study idicated occurrece of cotiuous ad sigificat loss of activities of most fluoroquioloes agaist S. aureus ad E. coli bacteraemic pathoges. Although ciprofloxaci was better tha other agets agaist S. aureus ad Klebsiella bacteraemia with ofloxaci servig as the treatmet optio agaist E. coli ad salmoella bacteraemia, resistace strais utreated with available fluoroquioloes appeared to have emerged i the regio. REFERENCES Acar JF., Goldstei FW. Treds i bacterial resistace to fluoroquioloes. Cli. Ifect. Dis.1997; (Suppl 1): S67-73 Asperilla MO., Smego RA., Scott LK. Quioloes activities i the treatmet of Salmoella ifectios. Rev. Ifect. Dis. 1990; 12: Austi DJ., Kristisso KG., Aderso RM. 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