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PubMed2001

The spread of a mupirocin-resistant/methicillin-resistant Staphylococcus aureus clone in Kuwait hospitals.

High-level mupirocin- and methicillin-resistant Staphylococcus aureus (MRSA) isolated from five hospitals in Kuwait were studied by pulsed-field gel electrophoresis (PFGE) to determine their relatedness to one another and to high-level mupirocin-resistant MRSA isolated previously in a Burns Unit. The genetic location of mupirocin resistance determinant was also determined. All of the isolates were resistant to gentamicin, kanamycin, streptomycin, tetracycline and cadmium, and contained plasmids of 38, 26 and 2.8 kb. Two isolates contained additional 4.4-kb plasmids. Transfer experiments demonstrated that the 38-kb plasmid encoded high-level mupirocin resistance and the 4.4-kb plasmid encoded chloramphenicol resistance. PFGE typing of representative isolates from the five hospitals demonstrated that the majority of them had identical or closely related pulsed-field patterns suggesting that they had a common origin. However, they differed from high-level mupirocin-resistant MRSA isolated previously in the Burns Unit in their resistance and pulsed-field patterns. Whereas the majority of the previous isolates were susceptible to ciprofloxacin and resistant to trimethoprim and chloramphenicol, the majority of the current isolates were susceptible to trimethoprim and chloramphenicol, and resistant to ciprofloxacin. Only one of the current isolates had identical pulsed-field pattern to the majority of isolates obtained previously in the Burns Unit. The results suggested that a previously dominant clone of high-level mupirocin-resistant MRSA has been replaced in the Burns Unit by a new clone, which also spread in four other hospitals.

Anti-Bacterial Agents↗
PubMed1989

Topical antibiotics in the treatment of superficial skin infections in general practice--a comparison of mupirocin with sodium fusidate.

A total of 413 eligible patients took part in an observer-blind randomised multicentre clinical trial in order to compare the clinical and bacteriological efficacy of mupirocin (Bactroban) ointment with sodium fusidate (Fucidin) ointment for treating superficial skin infections seen in general practice. Mupirocin was applied twice daily and sodium fusidate thrice daily for a period of 7 days. Both treatments were similarly effective with 97% patients treated with mupirocin and 93% patients treated with sodium fusidate responding. Mupirocin was significantly more effective in the treatment of acute primary skin infections and in the treatment of a subgroup of patients with impetigo (P less than 0.01). Of the organisms detected before treatment began, 93% were not found after treatment with mupirocin compared with 89% after treatment with sodium fusidate. Staphylococcus aureus and/or beta-haemolytic streptococci appeared to be eliminated in significantly more patients treated with mupirocin (96%) compared with those treated with sodium fusidate (88%), (P = 0.03). Both treatments were well tolerated.

Administration, Topical↗
PubMed1989

Topical 2% mupirocin versus 2% fusidic acid ointment in the treatment of primary and secondary skin infections.

The efficacy and side effects of topical mupirocin (Bactroban) and fusidic acid (Fucidin) ointment were compared in a double-blind, randomized trial in 70 patients who came to the Dermatologic Clinic of L'Enfant Jésus Hospital with primary or secondary (or both) skin infections. Thirty-five patients were treated with mupirocin and 35 patients were treated with fusidic acid three times a day for seven days. Clinical and bacteriologic assessments were conducted before and after treatment. The efficacy of mupirocin, in terms of resolution and improvement of clinical signs and symptoms of infection, as well as of the elimination of infecting organisms, was similar to that of fusidic acid. Of 34 patients (1 could not be evaluated) treated with mupirocin, a clinical cure was achieved in 18, and significant improvement was demonstrated in 15. Similarly, of 35 patients treated with fusidic acid, a clinical cure was achieved in 18 and improvement occurred in 15. Bacteriologic cure rates were 97% (30 of 31 patients evaluated) in the mupirocin-treated group, compared with 87% (27 of 31 patients evaluated) in the fusidic acid-treated group. No side effects were observed in either treatment group. Because topical 2% mupirocin has little or no potential for irritation, systemic side effects, or cross-resistance with other antibiotics, its efficacy is likely to make this new compound a useful agent for the treatment of superficial skin infections.

Administration, Topical↗
PubMed1998

Control of an outbreak of an epidemic methicillin-resistant Staphylococcus aureus also resistant to mupirocin.

An epidemic methicillin-resistant Staphlococcus aureus (EMRSA-3) appeared in a District hospital in June 1989 as part of a regional outbreak. The dynamics of the outbreak were complex and involved patient transfer between hospitals and wards. Control measures followed UK guidelines and included the use of nasal mupirocin. During these efforts a mupirocin-resistant MRSA [MuMRSA: mupirocin minimum inhibitor concentration (MIC) > 256 mg/L] emerged, probably in a patient who had been given eight mupirocin courses over nine months. The MuMRSA had a narrower phage-typing pattern than EMRSA-3, but was indistinguishable by pulsed-field gel electrophoresis of SmaI chromosomal restriction enzyme digests and its susceptibility pattern to other antibiotics. The results of in vitro curing and gene probing indicated that mupirocin resistance was encoded on a 48 Md plasmid. MuMRSA spread occurred in 12 patients and 11 staff. The affected patients were nursed on the same ward. The strain was eradicated from patients with oral ciprofloxacin and rifampicin, triclosan skin treatment and nasal fusidic acid and bacitracin cream. The control of the outbreak had significant medical, social and financial implications. Fortunately, there were alternative topical agents to mupirocin, an agent which has played such a key role in MRSA eradication in recent years.

Aged↗
PubMed1996

Clinical and economic effects of mupirocin calcium on preventing Staphylococcus aureus infection in hemodialysis patients: a decision analysis.

This study was performed to determine the clinical and economic consequences of alternative strategies of preventing Staphylococcus aureus infection in chronic hemodialysis patients by use of intranasal mupirocin calcium to clear nasal carriage of S aureus. Decision analysis evaluated clinical outcomes and cost-effectiveness of three likely management strategies to address S aureus nasal carriage and prevent subsequent infection in chronic ambulatory hemodialysis patients: (1) screen for S aureus nasal carriage every 3 months and treat those with a positive test result with mupirocin calcium; (2) treat all patients weekly with mupirocin calcium; or (3) no prevention strategy, treat infection only. Rates of nasal carriage of S aureus, S aureus infection rates, proportion of infections attributable to nasal carriage, efficacy of mupirocin, natural history of infection, and patient management strategies were derived from the published literature and supplemented by a panel of experts. Actual payments for medical services were obtained from Medicare parts A and B. Incremental cost-effectiveness was calculated from the perspective of Medicare and subjected to sensitivity analyses. Assuming that 75% of S aureus infections are attributable to nasal carriage in hemodialysis patients, eliminating nasal carriage of S aureus with mupirocin calcium (with or without screening) markedly reduces the number of infections (45% to 55%) and also reduces health care expenditures relative to treating infections when they occur. Annual savings to Medicare are $784,000 to $1,117,000 per 1,000 hemodialysis patients, depending on the prevention strategy. Preventing S aureus infection by eradicating nasal carriage in chronic hemodialysis patients reduces morbidity while simultaneously reducing medical care costs. The decision to eliminate nasal carriage on a regular basis or use a screening test to guide antibiotic therapy is dependent on the tradeoff between improved short-term clinical and cost benefits and the potential for bacterial resistance that may arise from widespread use of mupirocin calcium.

Administration, Intranasal↗
PubMed1999

A randomized clinical trial of mupirocin in the eradication of Staphylococcus aureus nasal carriage in human immunodeficiency virus disease.

Seventy-six human immunodeficiency virus (HIV)-infected patients with Staphylococcus aureus nasal carriage were randomized to treatment groups receiving intranasal mupirocin or placebo twice daily for 5 days. Nasal cultures for S. aureus were obtained at 1, 2, 6, and 10 weeks after therapy. At 1 week, 88% of mupirocin-treated patients had negative nasal cultures compared with 8% in placebo patients (P<.001). The percentage of mupirocin-treated patients with persistently negative nasal cultures decreased over time (63%, 45%, and 29% at 2, 6, and 10 weeks, respectively) but remained significantly greater than the placebo group (3% at 2, 6, and 10 weeks). In mupirocin-treated patients, most (16/19) instances of nasal recolonization were with pretreatment strains (determined by means of by pulsed field gel electrophoresis); mupirocin resistance was not observed. Five days of treatment with mupirocin eliminated S. aureus nasal carriage in HIV-infected patients for several weeks; however, since the effect waned over time, intermittent dosing regimens should be considered for long-term eradication.

AIDS-Related Opportunistic Infections↗
PubMed2002

Surgical site infections in orthopedic surgery: the effect of mupirocin nasal ointment in a double-blind, randomized, placebo-controlled study.

The objective of this study was to determine whether use of mupirocin nasal ointment for perioperative eradication of Staphylococcus aureus nasal carriage is effective in preventing the development of surgical site infections (SSIs). A randomized, double-blind, placebo-controlled design was used. Either mupirocin or placebo nasal ointment was applied twice daily to 614 assessable patients from the day of admission to the hospital until the day of surgery. A total of 315 and 299 patients were randomized to receive mupirocin and placebo, respectively. Eradication of nasal carriage was significantly more effective in the mupirocin group (eradication rate, 83.5% versus 27.8%). In the mupirocin group, the rate of endogenous S. aureus infections was 5 times lower than in the placebo group (0.3% and 1.7%, respectively; relative risk, 0.19; 95% confidence interval, 0.02-1.62). Mupirocin nasal ointment did not reduce the SSI rate (by S. aureus) or the duration of hospital stay.

Anti-Bacterial Agents↗
PubMed2003

Treatment of Staphylococcus aureus colonization and prophylaxis for infection with topical intranasal mupirocin: an evidence-based review.

Most Staphylococcus aureus infections are endogenously acquired, and treatment of nasal carriage is one potential strategy for prevention. We critically appraised the published evidence regarding the efficacy of intranasal mupirocin for eradication of S. aureus nasal carriage and for prophylaxis of infection. Sixteen randomized, controlled trials were appraised; 9 trials assessed eradication of colonization as a primary outcome measure, and 7 assessed the reduction in the rate of infection. Mupirocin was generally highly effective for eradication of nasal carriage in the short term. Prophylactic treatment of patients with intranasal mupirocin in large trials did not lead to a significant reduction in the overall rate of infections. However, subgroup analyses and several small studies revealed lower rates of S. aureus infection among selected populations of patients with nasal carriage treated with mupirocin. Although mupirocin is effective at reducing nasal carriage, routine use of topical intranasal mupirocin for infection prophylaxis is not supported by the currently available evidence.

Administration, Intranasal↗
PubMed2003

Mupirocin prophylaxis to prevent Staphylococcus aureus infection in patients undergoing dialysis: a meta-analysis.

A systematic review of the English-language literature was performed to determine the overall benefit of mupirocin therapy in reducing the rate of Staphylococcus aureus infection among patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). Included studies met the following criteria: they were randomized clinical trials or cohort studies; cohorts consisted of adults (age, > or =18 years) requiring HD or PD; mupirocin therapy was administered to the treatment group, and placebo or no therapy was administered to the control group; and the primary outcome of interest was the difference in the number of S. aureus infections among mupirocin-treated and -untreated patients. Ten studies described in 9 articles were analyzed. A total of 2445 patients were included in the analysis. Use of mupirocin reduced the rate of S. aureus infections by 68% (95% confidence interval [CI], 57%-76%) among all patients undergoing dialysis; risk reductions were 80% (95% CI, 65%-89%) among patients undergoing HD and 63% (95% CI, 50%-73%) among patients undergoing PD. When data were stratified by type of infection, S. aureus bacteremia was found to be reduced by 78% among patients undergoing HD, and peritonitis and exit-site infections were found to be reduced by 66% and 62%, respectively, among patients undergoing PD. Mupirocin prophylaxis substantially reduces the rate of S. aureus infection in the dialysis population. Optimal regimens that minimize the emergence of mupirocin resistance need to be explored.

Adult↗
PubMed1993

An outbreak of mupirocin-resistant Staphylococcus aureus on a dermatology ward associated with an environmental reservoir.

OBJECTIVE: To investigate a cluster of mupirocin-resistant Staphylococcus aureus on a dermatology ward. DESIGN: An outbreak of mupirocin-resistant S aureus was noted on the dermatology ward during a prospective epidemiologic study of methicillin-resistant S aureus (MRSA) and borderline methicillin-susceptible S aureus (BMSSA). Pulsed-field gel electrophoresis (PFGE) of whole-cell DNA digested with Sma I was used as a marker of strain identity. SETTING AND PATIENTS: An 850-bed university hospital with a 12-bed inpatient dermatology ward. Most patients have severe, exfoliating dermatologic disorders. RESULTS: MRSA or BMSSA were isolated from 13 patients on the dermatology ward over a 14-month period. Eleven of these isolates (84.6%) were mupirocin-resistant. Nine isolates were present on admission (81.8%); 8 of these patients had been hospitalized on the same ward within the last two months. Nasal and hand cultures from 36 personnel were negative for mupirocin-resistant MRSA or BMSSA. Extensive environmental culturing revealed that a blood pressure cuff and the patients' communal shower were positive for mupirocin-resistant BMSSA. PFGE of all mupirocin-resistant isolates demonstrated that the nine patients and both environmental sources had identical DNA typing patterns. INTERVENTIONS: Changing of blood pressure cuffs between patients and more stringent cleaning of communal areas was initiated. Repeat environmental cultures were negative. CONCLUSIONS: S aureus is not usually associated with an environmental reservoir; however, these patients all had severe desquamation, which may have prolonged environmental contamination.

Blood Pressure Determination↗
PubMed1988

Bactericidal efficacy of mupirocin in multi-antibiotic resistant Staphylococcus aureus burn wound infection.

Methicillin resistant Staphylococcus aureus strains (MRSA) have become increasingly prevalent as pathogenic organisms, especially in burn wounds, with an associated mortality of 20-40% among those clinically infected. Mupirocin ointment, a new topical antibiotic, has proved in vitro and in vivo to be highly effective in the treatment of MRSA infections. A modified Walker burn wound model was used to define the rate of trans-eschar penetration, biodynamic availability and bactericidal efficacy of 2% mupirocin ointment in established MRSA burn wound infection. In-vitro penetration trials confirmed the effective diffusion of mupirocin through 1.5 mm eschar within 2 h. A single topical application of mupirocin resulted in a 98.3% (5.67 x 10(8) cfu/g of tissue--1.0 x 10(7) cfu/g of tissue) reduction in intra-eschar viable organisms within 36 h post application. A second topical application of mupirocin at 24 h resulted in a total reduction of 99.6% in viable intra-eschar organisms (1.85 x 10(8) cfu/gram of tissue--6.76 x 10(5) cfu/g of tissue). It is concluded that mupirocin is highly effective in controlling MRSA burn wound infection and should be applied topically every 24 h.

Animals↗
PubMed1998

Evaluation of disc diffusion and Etest for determining the susceptibility of Staphylococcus aureus to mupirocin.

The susceptibilities to mupirocin of 102 selected clinical isolates of Staphylococcus aureus and of control strain S. aureus NCTC 6571 were determined by disc diffusion (using discs containing 5, 15, 25, 30, 50 and 200 microg of mupirocin) and Etest and the results were compared with MICs determined using an agar incorporation method. On the basis of agar incorporation MICs, 42 isolates were sensitive to mupirocin (MIC < or = 4 mg/L), 39 showed low-level resistance (MICs = 8-128 mg/L) and 22 were highly resistant (MICs > or = 256 mg/L) and contained the mupA resistance gene. Using Stokes' criteria, none of the discs used gave major errors (sensitive isolates classified as highly resistant) or very major errors (highly resistant isolates classified as sensitive) in assigning a category of susceptibility, but minor errors (a difference of one category) were noted with all strengths. The best correlation with agar incorporation MIC was obtained with 25 microg mupirocin discs, which classified correctly 98 (95%) isolates, while worse correlations were noted with 5 microg and 200 microg discs which are the only types currently available commercially, for which there were 47 and 30 minor errors, respectively. The MICs found by Etest were the same as, or lower than, those determined by agar incorporation. Etests classified correctly all 42 mupirocin-sensitive isolates, 19 (49%) low-level resistant isolates and 16 (73%) highly resistant isolates. Two isolates that contained the mupA gene and showed agar incorporation MICs of 256 mg/L and 512 mg/L were not classified as highly resistant by any of the diffusion methods used. Agar incorporation MIC determination, possibly supported by detection of the mupA gene, offers the most effective means of identifying high-level mupirocin resistance in S. aureus, although the Etest also proved to be reproducible. However, we conclude that 25 microg discs warrant further evaluation for possible use in clinical laboratories, as they appear to be more reliable than the discs currently available.

Anti-Bacterial Agents↗
PubMed2003

A chromosomal location of the mupA gene in Staphylococcus aureus expressing high-level mupirocin resistance.

OBJECTIVES: To investigate the genetic location of the mupA gene in high-level mupirocin-resistant Staphylococcus aureus isolates. MATERIALS AND METHODS: Antibiotic resistance was detected by disc diffusion. The Etest was used to determine mupirocin MIC. The presence of mupA was detected by PCR using specific primers. Curing, transfer experiments, pulsed-field gel electrophoresis (PFGE) and DNA hybridization were used to study the genetic location of mupA. RESULTS: The isolates had mupirocin MICs > 1024 mg/L and were resistant to methicillin, gentamicin, kanamycin, streptomycin, erythromycin, tetracycline, ciprofloxacin, cadmium acetate, propamidine isethionate and ethidium bromide. They carried two plasmids of approximately 26 and 2.8 kb. Curing and transfer experiments demonstrated that the 26 kb plasmid encoded resistance to cadmium acetate, propamidine isethionate and ethidium bromide. Loss of mupirocin resistance corresponded to the loss of a 40 kb DNA fragment from a 175 kb SmaI chromosomal fragment. The mupA gene was detected only in the genomic DNA of the mupirocin-resistant strains and in their derivatives cured of the 26 kb plasmid. A labelled mupA probe hybridized to the 175 kb SmaI fragment only in the mupirocin-resistant isolates. CONCLUSION: The absence of mupA on any of the plasmids and its detection only in the chromosomal DNA of the parents and in their derivatives cured of the 26 kb plasmid strongly supports a chromosomal location for mupA in these isolates.

Anti-Bacterial Agents↗
PubMed2003

Lack of efficacy of mupirocin in the prevention of infections with Staphylococcus aureus in liver transplant recipients and candidates.

BACKGROUND: Infections with Staphylococcus aureus are a significant problem in patients in liver transplant units. An association between prior nasal carriage with and subsequent infections has been documented previously in liver transplant recipients and patients with cirrhosis. However, the role of decolonization with mupirocin applied intranasally for the prevention of S. aureus infections in these patients has not been determined. METHODS: S. aureus nasal carriage was prospectively sought in 70 consecutive liver transplant candidates. Mupirocin two times per day for 5 days was administered to the carriers. Follow-up nasal cultures to document decolonization were performed 5 days after the final application of mupirocin. The primary endpoint was the development of S. aureus infections. RESULTS: Thirty-one of 70 patients (44%) were found to be nasal carriers and 27 of 31 nasal carriers (87%) were successfully decolonized. However, 12 of 27 patients (37%) successfully decolonized became recolonized with S. aureus, and an additional nine patients who were initially noncarriers became newly colonized with S. aureus during the study period. Despite the use of mupirocin, 16 of 70 patients (23%) developed an infection with S. aureus. No isolate was found to be mupirocin resistant. CONCLUSION: Elimination of S. aureus nasal carriage by mupirocin did not prevent S. aureus infections in patients in our liver transplant unit.

Adult↗
PubMed1988

Randomized clinical trial of topical mupirocin versus oral erythromycin for impetigo.

The safety and efficacy of a new topical antiinfective agent, mupirocin, was compared with that of oral erythromycin ethylsuccinate in the treatment of impetigo in children. Sixty-two children aged 5 months to 13 years with impetigo were assigned to be treated with either mupirocin in three daily applications or erythromycin ethylsuccinate (40 mg/kg of body weight per day divided into four doses) according to a randomized treatment schedule. On the initial visit, exudate or cleansed infected sites or both were cultured and therapy was begun. All patients were treated for 8 days. Patients were seen again on days 4 to 5 of therapy, at the end of therapy, and 7 days after the end of therapy. Sites of infection were comparable between the groups, as were bacteriologic responses. At the first visit, 24 of 30 children in the mupirocin group and 14 of 32 children in the erythromycin group were cured or had at least a 75% reduction in size of the lesions. At the end of the study, all 29 of the children in the mupirocin group who came to follow-up, compared with 27 of 29 in the erythromycin group, were cured. Side effects were few. Five children in the erythromycin group developed mild diarrhea. Thus, mupirocin appears to be safe and effective in treating impetigo in children. Our data show a trend toward more rapid clinical response with mupirocin than with erythromycin.

Administration, Oral↗
PubMed1989

Efficacy of mupirocin in methicillin-resistant Staphylococcus aureus burn wound infection.

Methicillin-resistant Staphylococcus aureus strains (MRSA) have become increasingly prevalent as nosocomial pathogens, especially in burn wounds. MRSA constituted 38% of all S. aureus isolates in our 25-bed burns unit despite the utilization of a combination of 1% silver sulfadiazine and 0.2% chlorhexidine as topical therapy. Mupirocin, a new antibiotic, has proved in vitro and in vivo to be highly effective in the treatment of MRSA infections. A prospective clinical trial with mupirocin ointment in MRSA burn wound infection was untertaken. Forty-five children with 59 discrete burn wounds and from whom MRSA were isolated were treated with 2% mupirocin ointment under occlusive dressings, applied twice daily for 5 days. The average burned area treated was 8% (range, 2 to 20%) of the total body surface area. The burn wounds were assessed clinically and bacteriologically daily. Mupirocin eliminated MRSA in all 59 wounds treated, with the maximum therapeutic response seen within 4 days. In three wounds, gram-negative organisms persisted after 5 days of topical therapy. Treatment was well tolerated by all children. We recommend that mupirocin in its present polyethylene glycol base should be used only on a selective basis, when current prophylactic topical therapy has failed to control MRSA infection in burns of less than 20% of the total body surface area, and that it should be applied only for a limited period of 5 days. The safety and the efficacy of mupirocin in burns exceeding 20% of the total body surface area need to be established.

Anti-Bacterial Agents↗
PubMed1995

Comparative study of mupirocin and oral co-trimoxazole plus topical fusidic acid in eradication of nasal carriage of methicillin-resistant Staphylococcus aureus.

Mupirocin is a topically applied drug that is very active in the eradication of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA). However, studies designed to compare mupirocin treatment with other antimicrobial regimens are lacking. We therefore conducted an open, prospective, randomized, controlled trial to compare the efficacy and safety of mupirocin versus those of oral co-trimoxazole plus topical fusidic acid (both regimens with a clorhexidine scrub bath) for the eradication of MRSA from nasal and extranasal carriers of MRSA. The eradication rates with mupirocin and co-trimoxazole plus fusidic acid at 2, 7, 14, 21, 28, and 90 days were 93 and of 93, 100 and 100, 97 and 94, 100 and 92, 96 and 95, and 78 and 71%, respectively, for nasal carriage. At 7, 14, and 28 days the eradication rates for extranasal carriage by the two regimens were 23 and 74, 83 and 76, and 45 and 69%, respectively. The efficacies and safety of both regimens were similar. The MRSA isolates were not resistant to the study drugs either at the baseline or at follow-up. These results suggest that mupirocin and co-trimoxazole plus fusidic acid, both used in conjunction with a chlorhexidine soap bath, are equally effective and safe for the eradication of MRSA from nasal and extranasal MRSA carriers. Mupirocin was easier to use but was more expensive.

Administration, Oral↗
PubMed2002

The bioavailability of mupirocin in nasal secretions in vitro.

AIM: To determine the bioavailability of mupirocin in human nasal secretions and to assess whether the contents of nasal secretions interact appreciably with this antibiotic. METHODS: The comparative bioavailability of mupirocin and chlorhexidine in nasal secretions was determined by bioassay after one, four, and eight hours of incubation with pooled secretions from three subjects. The interaction of mupirocin with nasal secretions was characterised by matrix assisted laser desorption time of flight mass spectrometry (MALDI-TOF). RESULTS: MALDI-TOF analysis showed that mupirocin was not absorbed by the main fraction of pooled nasal secretions and should remain active. In bioassay, mupirocin retained 100% of its antistaphylococcal activity in nasal secretions, whereas chlorhexidine was significantly reduced from 100 mg/litre to 1.5 mg/litre and from 1000 mg/litre to 38.5 mg/litre, irrespective of incubation time. CONCLUSIONS: The high bioavailability of mupirocin in nasal secretions results from the lack of appreciable molecular interactions.

Anti-Bacterial Agents↗